difference between peer review and research paper

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What is the Difference Between Research Papers and Review Papers?

Researchers often have to write different types of articles, from review papers to review papers and more, each with its own purpose and structure. This makes it critical for students and researchers to understand the nuances of good writing and develop the skills required to write various kinds of academic text. With so many different types of academic writing to pursue – scholarly articles, commentaries, book reviews, case reports, clinical study reports – it is common for students and early career researchers to get confused. So in this article, we will explain what is a review paper and what is a research paper, while summarizing the similarities and difference between review papers and research papers.

Table of Contents

What is a Review Paper ?

A review paper offers an overview of previously published work and does not contain any new research findings. It evaluates and summarizes information or knowledge that is already available in various published formats like journals, books, or other publications, all of which is referred to as secondary literature. Well-written review papers play a crucial role in helping students and researchers understand existing knowledge in a specific field or a research topic they are interested in. By providing a comprehensive overview of previous studies, methodologies, findings, and trends, they help researchers identify gaps in a specific field of study opening up new avenues for future research.

What is a Research Paper ?

A research paper is based on original research and primary sources of data. Unlike review papers, researchers writing research papers need to report new findings derived from empirical research or experimentation. It requires the author to draw inferences or make assumptions based on experiments, surveys, interviews, or questionnaires employed to collect and analyze data. Research papers also typically follow the recommended IMRAD format, which includes an abstract, introduction, methodology, results, discussion, and conclusion. Through research papers, authors address a specific research question or hypothesis with the aim of contributing novel insights to the field.

Similarities between research papers and review papers

Research papers and review papers share several similarities, which makes it understandable that it is this pair of academic documents that are often most confused.

• Research papers and review papers are written by scholars and intended for an academic audience; they’re written with the aim of contributing to the existing body of knowledge in a particular field and can be published in peer reviewed journals.
• Both research papers and review papers require a comprehensive understanding of all the latest, relevant literature on a specific topic. This means authors must conduct a thorough review of existing studies, theories, and methodologies in their own subject and related areas to inform their own research or analysis.
• Research papers and review papers both adhere to specific formatting and citation styles dictated by the target journal. This ensures consistency and allows readers to easily locate and reference the sources cited in the papers.

These similarities highlight the rigorous, scholarly nature of both research papers and review papers, which requires both research integrity and a commitment to further knowledge in a field. However, these two types of academic writing are more different than one would think.

Differences between research papers and review papers

Though often used interchangeably to refer to academic content, research papers and review papers are quite different. They have different purposes, specific structure and writing styles, and citation formats given that they aim to communicate different kinds of information. Here are four key differences between research papers and review papers:

• Purpose: Review papers evaluate existing research, identify trends, and discuss the current state of knowledge on a specific topic; they are based on the study of previously published literature. On the other hand, research paperscontain original research work undertaken by the author, who is required to contribute new knowledge to the research field.
• Structure: Research papers typically follow a structured format, including key sections like the introduction, methods, results, discussion, and conclusion. Meanwhile, review papers may have a more flexible structure, allowing authors to organize the content based on thematic or chronological approaches. However, they generally include an introduction, main body discussing various aspects of the topic, and a conclusion.
• Methodology: Research papers involve the collection of data, experimentation, or analysis of existing data to answer specific research questions. However, review papers do not involve original data collection; instead, they extensively analyze and summarize existing studies, often using systematic literature review methods.
• Citation style: Research papers rely on primary sources to support and justify their own findings, emphasizing recent and relevant research. Review papers incorporate a wide range of primary and secondary sources to present a comprehensive overview of the topic and support the evaluation and synthesis of existing literature.

In summary, it’s important to understand the key differences between research papers and review papers. By mastering the art of writing both research papers and review papers, students and researchers can make more meaningful contributions to their chosen disciplines. All the best!

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• What Is Peer Review? | Types & Examples

What Is Peer Review? | Types & Examples

Published on December 17, 2021 by Tegan George . Revised on June 22, 2023.

Peer review, sometimes referred to as refereeing , is the process of evaluating submissions to an academic journal. Using strict criteria, a panel of reviewers in the same subject area decides whether to accept each submission for publication.

Peer-reviewed articles are considered a highly credible source due to the stringent process they go through before publication.

There are various types of peer review. The main difference between them is to what extent the authors, reviewers, and editors know each other’s identities. The most common types are:

• Single-blind review
• Double-blind review
• Triple-blind review

Collaborative review

Open review.

Relatedly, peer assessment is a process where your peers provide you with feedback on something you’ve written, based on a set of criteria or benchmarks from an instructor. They then give constructive feedback, compliments, or guidance to help you improve your draft.

Table of contents

What is the purpose of peer review, types of peer review, the peer review process, providing feedback to your peers, peer review example, advantages of peer review, criticisms of peer review, other interesting articles, frequently asked questions about peer reviews.

Many academic fields use peer review, largely to determine whether a manuscript is suitable for publication. Peer review enhances the credibility of the manuscript. For this reason, academic journals are among the most credible sources you can refer to.

However, peer review is also common in non-academic settings. The United Nations, the European Union, and many individual nations use peer review to evaluate grant applications. It is also widely used in medical and health-related fields as a teaching or quality-of-care measure.

Peer assessment is often used in the classroom as a pedagogical tool. Both receiving feedback and providing it are thought to enhance the learning process, helping students think critically and collaboratively.

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Depending on the journal, there are several types of peer review.

Single-blind peer review

The most common type of peer review is single-blind (or single anonymized) review . Here, the names of the reviewers are not known by the author.

While this gives the reviewers the ability to give feedback without the possibility of interference from the author, there has been substantial criticism of this method in the last few years. Many argue that single-blind reviewing can lead to poaching or intellectual theft or that anonymized comments cause reviewers to be too harsh.

Double-blind peer review

In double-blind (or double anonymized) review , both the author and the reviewers are anonymous.

Arguments for double-blind review highlight that this mitigates any risk of prejudice on the side of the reviewer, while protecting the nature of the process. In theory, it also leads to manuscripts being published on merit rather than on the reputation of the author.

Triple-blind peer review

While triple-blind (or triple anonymized) review —where the identities of the author, reviewers, and editors are all anonymized—does exist, it is difficult to carry out in practice.

Proponents of adopting triple-blind review for journal submissions argue that it minimizes potential conflicts of interest and biases. However, ensuring anonymity is logistically challenging, and current editing software is not always able to fully anonymize everyone involved in the process.

In collaborative review , authors and reviewers interact with each other directly throughout the process. However, the identity of the reviewer is not known to the author. This gives all parties the opportunity to resolve any inconsistencies or contradictions in real time, and provides them a rich forum for discussion. It can mitigate the need for multiple rounds of editing and minimize back-and-forth.

Collaborative review can be time- and resource-intensive for the journal, however. For these collaborations to occur, there has to be a set system in place, often a technological platform, with staff monitoring and fixing any bugs or glitches.

Lastly, in open review , all parties know each other’s identities throughout the process. Often, open review can also include feedback from a larger audience, such as an online forum, or reviewer feedback included as part of the final published product.

While many argue that greater transparency prevents plagiarism or unnecessary harshness, there is also concern about the quality of future scholarship if reviewers feel they have to censor their comments.

In general, the peer review process includes the following steps:

• First, the author submits the manuscript to the editor.
• Reject the manuscript and send it back to the author, or
• Send it onward to the selected peer reviewer(s)
• Next, the peer review process occurs. The reviewer provides feedback, addressing any major or minor issues with the manuscript, and gives their advice regarding what edits should be made.
• Lastly, the edited manuscript is sent back to the author. They input the edits and resubmit it to the editor for publication.

In an effort to be transparent, many journals are now disclosing who reviewed each article in the published product. There are also increasing opportunities for collaboration and feedback, with some journals allowing open communication between reviewers and authors.

It can seem daunting at first to conduct a peer review or peer assessment. If you’re not sure where to start, there are several best practices you can use.

Summarize the argument in your own words

Summarizing the main argument helps the author see how their argument is interpreted by readers, and gives you a jumping-off point for providing feedback. If you’re having trouble doing this, it’s a sign that the argument needs to be clearer, more concise, or worded differently.

If the author sees that you’ve interpreted their argument differently than they intended, they have an opportunity to address any misunderstandings when they get the manuscript back.

Separate your feedback into major and minor issues

It can be challenging to keep feedback organized. One strategy is to start out with any major issues and then flow into the more minor points. It’s often helpful to keep your feedback in a numbered list, so the author has concrete points to refer back to.

Major issues typically consist of any problems with the style, flow, or key points of the manuscript. Minor issues include spelling errors, citation errors, or other smaller, easy-to-apply feedback.

Tip: Try not to focus too much on the minor issues. If the manuscript has a lot of typos, consider making a note that the author should address spelling and grammar issues, rather than going through and fixing each one.

The best feedback you can provide is anything that helps them strengthen their argument or resolve major stylistic issues.

Give the type of feedback that you would like to receive

No one likes being criticized, and it can be difficult to give honest feedback without sounding overly harsh or critical. One strategy you can use here is the “compliment sandwich,” where you “sandwich” your constructive criticism between two compliments.

Be sure you are giving concrete, actionable feedback that will help the author submit a successful final draft. While you shouldn’t tell them exactly what they should do, your feedback should help them resolve any issues they may have overlooked.

As a rule of thumb, your feedback should be:

• Easy to understand
• Constructive

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Below is a brief annotated research example. You can view examples of peer feedback by hovering over the highlighted sections.

Influence of phone use on sleep

Studies show that teens from the US are getting less sleep than they were a decade ago (Johnson, 2019) . On average, teens only slept for 6 hours a night in 2021, compared to 8 hours a night in 2011. Johnson mentions several potential causes, such as increased anxiety, changed diets, and increased phone use.

The current study focuses on the effect phone use before bedtime has on the number of hours of sleep teens are getting.

For this study, a sample of 300 teens was recruited using social media, such as Facebook, Instagram, and Snapchat. The first week, all teens were allowed to use their phone the way they normally would, in order to obtain a baseline.

The sample was then divided into 3 groups:

• Group 1 was not allowed to use their phone before bedtime.
• Group 2 used their phone for 1 hour before bedtime.
• Group 3 used their phone for 3 hours before bedtime.

All participants were asked to go to sleep around 10 p.m. to control for variation in bedtime . In the morning, their Fitbit showed the number of hours they’d slept. They kept track of these numbers themselves for 1 week.

Two independent t tests were used in order to compare Group 1 and Group 2, and Group 1 and Group 3. The first t test showed no significant difference ( p > .05) between the number of hours for Group 1 ( M = 7.8, SD = 0.6) and Group 2 ( M = 7.0, SD = 0.8). The second t test showed a significant difference ( p < .01) between the average difference for Group 1 ( M = 7.8, SD = 0.6) and Group 3 ( M = 6.1, SD = 1.5).

This shows that teens sleep fewer hours a night if they use their phone for over an hour before bedtime, compared to teens who use their phone for 0 to 1 hours.

Peer review is an established and hallowed process in academia, dating back hundreds of years. It provides various fields of study with metrics, expectations, and guidance to ensure published work is consistent with predetermined standards.

• Protects the quality of published research

Peer review can stop obviously problematic, falsified, or otherwise untrustworthy research from being published. Any content that raises red flags for reviewers can be closely examined in the review stage, preventing plagiarized or duplicated research from being published.

• Gives you access to feedback from experts in your field

Peer review represents an excellent opportunity to get feedback from renowned experts in your field and to improve your writing through their feedback and guidance. Experts with knowledge about your subject matter can give you feedback on both style and content, and they may also suggest avenues for further research that you hadn’t yet considered.

• Helps you identify any weaknesses in your argument

Peer review acts as a first defense, helping you ensure your argument is clear and that there are no gaps, vague terms, or unanswered questions for readers who weren’t involved in the research process. This way, you’ll end up with a more robust, more cohesive article.

While peer review is a widely accepted metric for credibility, it’s not without its drawbacks.

• Reviewer bias

The more transparent double-blind system is not yet very common, which can lead to bias in reviewing. A common criticism is that an excellent paper by a new researcher may be declined, while an objectively lower-quality submission by an established researcher would be accepted.

• Delays in publication

The thoroughness of the peer review process can lead to significant delays in publishing time. Research that was current at the time of submission may not be as current by the time it’s published. There is also high risk of publication bias , where journals are more likely to publish studies with positive findings than studies with negative findings.

• Risk of human error

By its very nature, peer review carries a risk of human error. In particular, falsification often cannot be detected, given that reviewers would have to replicate entire experiments to ensure the validity of results.

If you want to know more about statistics , methodology , or research bias , make sure to check out some of our other articles with explanations and examples.

• Normal distribution
• Measures of central tendency
• Chi square tests
• Confidence interval
• Quartiles & Quantiles
• Cluster sampling
• Stratified sampling
• Thematic analysis
• Discourse analysis
• Cohort study
• Ethnography

Research bias

• Implicit bias
• Cognitive bias
• Conformity bias
• Hawthorne effect
• Availability heuristic
• Attrition bias
• Social desirability bias

Peer review is a process of evaluating submissions to an academic journal. Utilizing rigorous criteria, a panel of reviewers in the same subject area decide whether to accept each submission for publication. For this reason, academic journals are often considered among the most credible sources you can use in a research project– provided that the journal itself is trustworthy and well-regarded.

In general, the peer review process follows the following steps: 

• Reject the manuscript and send it back to author, or 
• Send it onward to the selected peer reviewer(s) 
• Next, the peer review process occurs. The reviewer provides feedback, addressing any major or minor issues with the manuscript, and gives their advice regarding what edits should be made. 
• Lastly, the edited manuscript is sent back to the author. They input the edits, and resubmit it to the editor for publication.

Peer review can stop obviously problematic, falsified, or otherwise untrustworthy research from being published. It also represents an excellent opportunity to get feedback from renowned experts in your field. It acts as a first defense, helping you ensure your argument is clear and that there are no gaps, vague terms, or unanswered questions for readers who weren’t involved in the research process.

Peer-reviewed articles are considered a highly credible source due to this stringent process they go through before publication.

Many academic fields use peer review , largely to determine whether a manuscript is suitable for publication. Peer review enhances the credibility of the published manuscript.

However, peer review is also common in non-academic settings. The United Nations, the European Union, and many individual nations use peer review to evaluate grant applications. It is also widely used in medical and health-related fields as a teaching or quality-of-care measure. 

A credible source should pass the CRAAP test  and follow these guidelines:

• The information should be up to date and current.
• The author and publication should be a trusted authority on the subject you are researching.
• The sources the author cited should be easy to find, clear, and unbiased.
• For a web source, the URL and layout should signify that it is trustworthy.

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Peer Reviewed Literature

What is peer review, terminology, peer review what does that mean, what types of articles are peer-reviewed, what information is not peer-reviewed, what about google scholar.

• How do I find peer-reviewed articles?
• Scholarly vs. Popular Sources

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This Guide was created by Carolyn Swidrak (retired).

Research findings are communicated in many ways.  One of the most important ways is through publication in scholarly, peer-reviewed journals.

Research published in scholarly journals is held to a high standard.  It must make a credible and significant contribution to the discipline.  To ensure a very high level of quality, articles that are submitted to scholarly journals undergo a process called peer-review.

Once an article has been submitted for publication, it is reviewed by other independent, academic experts (at least two) in the same field as the authors.  These are the peers.  The peers evaluate the research and decide if it is good enough and important enough to publish.  Usually there is a back-and-forth exchange between the reviewers and the authors, including requests for revisions, before an article is published. 

Peer review is a rigorous process but the intensity varies by journal.  Some journals are very prestigious and receive many submissions for publication.  They publish only the very best, most highly regarded research. 

The terms scholarly, academic, peer-reviewed and refereed are sometimes used interchangeably, although there are slight differences.

Scholarly and academic may refer to peer-reviewed articles, but not all scholarly and academic journals are peer-reviewed (although most are.)  For example, the Harvard Business Review is an academic journal but it is editorially reviewed, not peer-reviewed.

Peer-reviewed and refereed are identical terms.

From  Peer Review in 3 Minutes  [Video], by the North Carolina State University Library, 2014, YouTube (https://youtu.be/rOCQZ7QnoN0).

Peer reviewed articles can include:

• Original research (empirical studies)
• Review articles
• Systematic reviews
• Meta-analyses

There is much excellent, credible information in existence that is NOT peer-reviewed.  Peer-review is simply ONE MEASURE of quality. 

Much of this information is referred to as "gray literature."

Government Agencies

Government websites such as the Centers for Disease Control (CDC) publish high level, trustworthy information.  However, most of it is not peer-reviewed.  (Some of their publications are peer-reviewed, however. The journal Emerging Infectious Diseases, published by the CDC is one example.)

Conference Proceedings

Papers from conference proceedings are not usually peer-reviewed.  They may go on to become published articles in a peer-reviewed journal. 

Dissertations

Dissertations are written by doctoral candidates, and while they are academic they are not peer-reviewed.

Many students like Google Scholar because it is easy to use.  While the results from Google Scholar are generally academic they are not necessarily peer-reviewed.  Typically, you will find:

• Peer reviewed journal articles (although they are not identified as peer-reviewed)
• Unpublished scholarly articles (not peer-reviewed)
• Masters theses, doctoral dissertations and other degree publications (not peer-reviewed)
• Book citations and links to some books (not necessarily peer-reviewed)
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Peer Review in Three Minutes from NC State University Libraries on Vimeo

A peer reviewed  or  peer refereed  journal or article is one in which a group of widely acknowledged experts in a field reviews the content for scholarly soundness and academic value.

Scholarly vs. Popular Articles

• Scholarly Articles
• Popular Articles

Example of a Scholarly Article

Note the Author's credentials, abstract, and citations in the text. These features indicate that the article is scholarly.

Scholarly articles often have abstracts, footnotes or citations, and list the author's credentials.

Learn more about the difference between scholarly and popular resources on our Evaluating Resources guide . 

Example of a Popular Article

Popular articles, like this one from Scientific American  may be from a reputable publication but not peer-reviewed. The Author may or may not be an academic, but the article is written for a popular audience. There are no footnotes or citations.

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• Scholarly Journals and Popular Magazines
• Differences in Research, Review, and Opinion Articles

Scholarly Journals and Popular Magazines: Differences in Research, Review, and Opinion Articles

• Where Do I Start?
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• How Do I Compare Periodical Types?
• Where Can I find More Information?

Research Articles, Reviews, and Opinion Pieces

Scholarly or research articles are written for experts in their fields. They are often peer-reviewed or reviewed by other experts in the field prior to publication. They often have terminology or jargon that is field specific. They are generally lengthy articles. Social science and science scholarly articles have similar structures as do arts and humanities scholarly articles. Not all items in a scholarly journal are peer reviewed. For example, an editorial opinion items can be published in a scholarly journal but the article itself is not scholarly. Scholarly journals may include book reviews or other content that have not been peer reviewed.

Empirical Study: (Original or Primary) based on observation, experimentation, or study. Clinical trials, clinical case studies, and most meta-analyses are empirical studies.

Review Article: (Secondary Sources) Article that summarizes the research in a particular subject, area, or topic. They often include a summary, an literature reviews, systematic reviews, and meta-analyses.

Clinical case study (Primary or Original sources): These articles provide real cases from medical or clinical practice. They often include symptoms and diagnosis.

Clinical trials ( Health Research): Th ese articles are often based on large groups of people. They often include methods and control studies. They tend to be lengthy articles.

Opinion Piece:  An opinion piece often includes personal thoughts, beliefs, or feelings or a judgement or conclusion based on facts. The goal may be to persuade or influence the reader that their position on this topic is the best.

Book review: Recent review of books in the field. They may be several pages but tend to be fairly short. 

Social Science and Science Research Articles

The majority of social science and physical science articles include

• Journal Title and Author
• Abstract 
• Introduction with a hypothesis or thesis
• Literature Review
• Methods/Methodology
• Results/Findings

Arts and Humanities Research Articles

In the Arts and Humanities, scholarly articles tend to be less formatted than in the social sciences and sciences. In the humanities, scholars are not conducting the same kinds of research experiments, but they are still using evidence to draw logical conclusions.  Common sections of these articles include:

• an Introduction
• Discussion/Conclusion
• works cited/References/Bibliography

Research versus Review Articles

• 6 Article types that journals publish: A guide for early career researchers
• INFOGRAPHIC: 5 Differences between a research paper and a review paper
• Michigan State University. Empirical vs Review Articles
• UC Merced Library. Empirical & Review Articles
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Need to find peer reviewed articles, but not sure what that means? Here are the differences between key publication types

Peer review means that a board of scholarly reviewers in the subject area of the journal review materials they publish for quality of research and adherence to editorial standards of the journal before articles are accepted for publication. If you use materials from peer-reviewed publications they have been vetted by scholars in your field for quality and importance.   

The kinds of articles students encounter most are scholarly journal articles, popular magazine and newspaper articles, and trade publication articles. This chart explains the major distinctions between these types of publications that publish articles. 

Written by: Brittany Geissinger and Linda Salem

Wait, there's more! Local Newspapers and Business Publications are also useful:

When your business research is focused on the performance of an industry in a particular region, the overall economy of a particular region, or a company that is headquartered in a particular place, local newspapers and regional business publications are an excellent source. These publications are also useful for overall industry research if the industry is predominantly located in a particular place. For example, San Francisco and Bay Area publications will give insight into the overall tech industry, and New York or L.A. publications will give insight into the overall film industry.

Example San Diego Publications:

The San Diego Union-Tribune's Business Section (Local Newspaper)

Crain's San Diego (Local Business News)

Finding Trade Publications:

There are multiple useful sources, such as the book linked below, for finding trade journals, but ChatGPT and other AI/LLM can be useful for finding trade journals.

• Example ChatGPT/AI/LLM search: "what are the best trade journals or industry news sources for the cybersecurity industry? Only include results with active websites."

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Difference between Research Paper and Review Paper

A research paper is written by students in which they have to conduct research on a given topic and then write the content. A review paper consists of reviews related to different articles that are already published. In this article, we will discuss the difference between a research paper and a review paper.

Research Paper

A research paper is an academic writing in which students have to collect information related to a given topic. They have to make an organized report regarding the subject which can include the research they have conducted or the research already done by other students. A peer review has to be conducted before publishing.

Steps to Write a Research Paper

Students have to follow the steps below to write a perfect research paper. These steps are discussed here.

The given assignment should be perfectly understood

Choose a topic, look for the sources of information.

• The thesis statement should be developed
• An outline of the research paper should be created

Write the first draft

Write the paragraphs properly, write the introduction, body text should be compelling, conclude the research paper, revise the research paper.

Before writing a research paper you have to understand the given assignment and then decide the specific tasks that you have to do to complete it. Here are the things that you need to do −

• Read the assignment and look for the topics that can create confusion
• Decide the length of the paper along with the options of formatting
• Make a bulleted list of all headings that you will add and then write about them
• Consider the deadline and decide the length of the research paper

Choose a topic about which you can get a large amount of content. The topic should be of your interest. You can do your own research or take help from research done by other people.

The next thing that you have to do is look for the sources from where you can get the information about the topic. Some of these sources can be discussions, books, journals, and websites. Look for the following −

• Heated debates
• Unique ideas
• Recent developments
• Overlooked but important topics

All these things will help you in devising questions related to your research topic.

Thesis statement should be developed

The next step is to develop a thesis statement which is an answer to the research question. Your answer should be supported by reasoning and pieces of evidence. The length of the thesis statement should be short and summarized.

Outline of the research paper should be created

Create an outline for the research which should include key topics, evidence, and arguments. They should be further divided into headings. This division will be helpful in writing the paper efficiently.

Write the first draft of the research paper with proper order and formatting. Your ideas should be clearly described and paragraphs should be ordered logically. You can start with the easiest or the most difficult topic. There can be situations where you have written a large amount of content for a topic. Rather than deleting it, take some part of it and paste it into another document which can be used later.

The paragraphs should be properly organized and it is better if you write each idea in a small and single paragraph. Each paragraph should not be more than three to four lines.

Now the time has come to write the introduction which should answer three questions related to your topics and these questions are what, why, and how.

This is the major part of your research paper and you may face difficulties in writing it. If you have created an outline, writing will be easy. The body text should be compelling so that the reader gets engaged in reading.

Write the conclusion of your research paper which should give a final touch to the content. Readers should understand the ways that you have used to write the paper. You can also include questions which your readers can try to answer.

Read the whole research paper and find if there is any spelling, grammatical, or factual mistakes. Check the structure of the paragraph and sentences. If there is a very long sentence, try to break it as it may become confusing for the readers.

Length of the Research Paper

The length of the research paper can be between 4,000 to 8,000 words. The minimum word count can be 2,000 and the maximum can go beyond 10,000 depending on the topic.

Review Papers

A review paper is an article which consists of surveys of the articles that are already published. No new experimental results are included in these articles. Other names of the review paper are literature review or review of literature. New conclusions can be drawn from the existing article. Review articles can explore new areas of research from the existing studies.

Steps to Write a Review Paper

Here are the steps that you have to follow to write a review paper.

Look for the aim of the article for which the review is to be written

Scope should be defined, look for the sources, choose title and keywords, topic should be introduced, critical discussion should be included, conclude the review paper.

Read the article and know about the aim and scope. All the articles do not accept reviews so you need to be very careful while choosing the article for which the review is to be written.

Find the research question and answer it with the aim of adding something new to the topic. The review should neither be too small nor too large. It should be managed easily.

You can look for the sources through search engines, books, and others. The search engines will provide a lot of sources which you can use to write the review.

Choose a proper title for your review article along with the keywords. The title will help to improve the number of views online. It will get more views if the correct readers view your article. The title should be concise, clear, and accurate and provide good information.

Write the introduction about the topic giving the reason for providing the review. The introduction should reach a large number of people which should also include non-specialists.

A critical discussion should also be included in the review paper. If the research topic is contradictory, a debate can also be included which should consist of arguments from both sides. The review paper should have the ability of resolving the conflict between contradictory studies.

A conclusion should be included at the end of the review paper. This should include the things that you have understood after studying the topic for which the review has been written.

Difference between Research paper and Review Paper

There are many differences between a research paper and a review paper and the table below includes them −

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What is the difference between a review paper and a research paper?

I have been working on a review paper. After publication, how will it add on my academic research profile? When I will apply for MS or PHD admission, will it count as publication?

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5 Answers 5

A review paper is likely also known as a "survey paper", where you read (i.e. survey) related works in the field and then comment on them. Usually, a review paper should be able to contribute a small amount of knowledge in its own right to the field by providing a taxonomy of work.

Another type of paper that reviews extensively related work but isn't actually a review paper is a "systematic review paper" in which you usually ask a meta-question about the field.

If it appears in a refereed, peer-reviewed journal, then yes, it is a publication. In fact, if done well, these works can often have pretty high impact and can be cited very frequently. However, as already noted, since they don't usually involve substantial original research they need to be augmented with traditional research papers. If a graduate student has only survey papers or systematic review papers, I'd wonder as a search committee reviewer if this student did nothing but read related work rather than working on research.

With respect to MS or PhD applications, I'd think that the fact that you have a publication at all is already a bonus point for you. Most students who apply to these programs don't have publications.

One important distinction should be made between papers in the humanities and the sciences. In the sciences, it would be much more important to have "original research" papers where new ground is broken. In the humanities, by contrast, the act of studying the existing literature and critically evaluating it may, in and of itself, be considered an act of research. (Similarly, in medicine, "meta-studies" in which the reports of various experiments are synthesized to produce overall results and recommendations may also be considered very important, although they augment direct clinical research, rather than substitute for it.)

I have limited experience regarding since I am still a graduate student but from what I understand, a review paper is also a research paper. However, unlike a piece of research, where you study the existing literature, develop research questions and hypotheses, collect data, run experiments/analysis and make inferences which accept or reject your hypotheses, a review article is a summarization and collation of existing articles in a given, specific research topic.

There has been some semi-formal writings on this already namely, this and this . The consensus, so far, seems to be that review articles make fine additions to your publication record but not as fine as articles where you actually did your own research.

I have little experience, because I am still an undergraduate student but from what I understand:

• Research paper: A paper in which results and discussion are derived from an experiment.
• Review paper: A paper in which results and discussion are not described.

• 4 Welcome to Academia SE. I have to disagree with your definitions. A research paper does not need to be based on an experiment (e.g., many mathematical papers). Also, a paper which does not describe (or derive) its results and discussions is just a very bad paper – this has nothing to do with the paper being a research or review paper. –  Wrzlprmft ♦ Commented Nov 26, 2014 at 15:19

I would describe a review paper as different from a research paper. A research paper is one's original work that may be researched scientifically or otherwise, but a review paper is where someone goes through work already done/researched and gives suggestions as per that field of research. The suggestions would be if the objective, goal, problem were met by the researcher. Whether the research is of value now or in future, solutions to the problem, what is interesting, etc.

• Welcome to Academia SE. You seem to be confusing a review paper with a peer review. The downvotes you are receiving are likely due to this, i.e., to indicate that your answer is wrong. Do not take them personally. –  Wrzlprmft ♦ Commented Oct 21, 2015 at 11:27

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Writing a Scientific Review Article: Comprehensive Insights for Beginners

Ayodeji amobonye.

1 Department of Biotechnology and Food Science, Faculty of Applied Sciences, Durban University of Technology, P.O. Box 1334, KwaZulu-Natal, Durban 4000, South Africa

2 Writing Centre, Durban University of Technology, P.O. Box 1334 KwaZulu-Natal, Durban 4000, South Africa

Japareng Lalung

3 School of Industrial Technology, Universiti Sains Malaysia, Gelugor 11800, Pulau Pinang, Malaysia

Santhosh Pillai

Associated data.

The data and materials that support the findings of this study are available from the corresponding author upon reasonable request.

Review articles present comprehensive overview of relevant literature on specific themes and synthesise the studies related to these themes, with the aim of strengthening the foundation of knowledge and facilitating theory development. The significance of review articles in science is immeasurable as both students and researchers rely on these articles as the starting point for their research. Interestingly, many postgraduate students are expected to write review articles for journal publications as a way of demonstrating their ability to contribute to new knowledge in their respective fields. However, there is no comprehensive instructional framework to guide them on how to analyse and synthesise the literature in their niches into publishable review articles. The dearth of ample guidance or explicit training results in students having to learn all by themselves, usually by trial and error, which often leads to high rejection rates from publishing houses. Therefore, this article seeks to identify these challenges from a beginner's perspective and strives to plug the identified gaps and discrepancies. Thus, the purpose of this paper is to serve as a systematic guide for emerging scientists and to summarise the most important information on how to write and structure a publishable review article.

1. Introduction

Early scientists, spanning from the Ancient Egyptian civilization to the Scientific Revolution of the 16 th /17 th century, based their research on intuitions, personal observations, and personal insights. Thus, less time was spent on background reading as there was not much literature to refer to. This is well illustrated in the case of Sir Isaac Newton's apple tree and the theory of gravity, as well as Gregor Mendel's pea plants and the theory of inheritance. However, with the astronomical expansion in scientific knowledge and the emergence of the information age in the last century, new ideas are now being built on previously published works, thus the periodic need to appraise the huge amount of already published literature [ 1 ]. According to Birkle et al. [ 2 ], the Web of Science—an authoritative database of research publications and citations—covered more than 80 million scholarly materials. Hence, a critical review of prior and relevant literature is indispensable for any research endeavour as it provides the necessary framework needed for synthesising new knowledge and for highlighting new insights and perspectives [ 3 ].

Review papers are generally considered secondary research publications that sum up already existing works on a particular research topic or question and relate them to the current status of the topic. This makes review articles distinctly different from scientific research papers. While the primary aim of the latter is to develop new arguments by reporting original research, the former is focused on summarising and synthesising previous ideas, studies, and arguments, without adding new experimental contributions. Review articles basically describe the content and quality of knowledge that are currently available, with a special focus on the significance of the previous works. To this end, a review article cannot simply reiterate a subject matter, but it must contribute to the field of knowledge by synthesising available materials and offering a scholarly critique of theory [ 4 ]. Typically, these articles critically analyse both quantitative and qualitative studies by scrutinising experimental results, the discussion of the experimental data, and in some instances, previous review articles to propose new working theories. Thus, a review article is more than a mere exhaustive compilation of all that has been published on a topic; it must be a balanced, informative, perspective, and unbiased compendium of previous studies which may also include contrasting findings, inconsistencies, and conventional and current views on the subject [ 5 ].

Hence, the essence of a review article is measured by what is achieved, what is discovered, and how information is communicated to the reader [ 6 ]. According to Steward [ 7 ], a good literature review should be analytical, critical, comprehensive, selective, relevant, synthetic, and fully referenced. On the other hand, a review article is considered to be inadequate if it is lacking in focus or outcome, overgeneralised, opinionated, unbalanced, and uncritical [ 7 ]. Most review papers fail to meet these standards and thus can be viewed as mere summaries of previous works in a particular field of study. In one of the few studies that assessed the quality of review articles, none of the 50 papers that were analysed met the predefined criteria for a good review [ 8 ]. However, beginners must also realise that there is no bad writing in the true sense; there is only writing in evolution and under refinement. Literally, every piece of writing can be improved upon, right from the first draft until the final published manuscript. Hence, a paper can only be referred to as bad and unfixable when the author is not open to corrections or when the writer gives up on it.

According to Peat et al. [ 9 ], “everything is easy when you know how,” a maxim which applies to scientific writing in general and review writing in particular. In this regard, the authors emphasized that the writer should be open to learning and should also follow established rules instead of following a blind trial-and-error approach. In contrast to the popular belief that review articles should only be written by experienced scientists and researchers, recent trends have shown that many early-career scientists, especially postgraduate students, are currently expected to write review articles during the course of their studies. However, these scholars have little or no access to formal training on how to analyse and synthesise the research literature in their respective fields [ 10 ]. Consequently, students seeking guidance on how to write or improve their literature reviews are less likely to find published works on the subject, particularly in the science fields. Although various publications have dealt with the challenges of searching for literature, or writing literature reviews for dissertation/thesis purposes, there is little or no information on how to write a comprehensive review article for publication. In addition to the paucity of published information to guide the potential author, the lack of understanding of what constitutes a review paper compounds their challenges. Thus, the purpose of this paper is to serve as a guide for writing review papers for journal publishing. This work draws on the experience of the authors to assist early-career scientists/researchers in the “hard skill” of authoring review articles. Even though there is no single path to writing scientifically, or to writing reviews in particular, this paper attempts to simplify the process by looking at this subject from a beginner's perspective. Hence, this paper highlights the differences between the types of review articles in the sciences while also explaining the needs and purpose of writing review articles. Furthermore, it presents details on how to search for the literature as well as how to structure the manuscript to produce logical and coherent outputs. It is hoped that this work will ease prospective scientific writers into the challenging but rewarding art of writing review articles.

2. Benefits of Review Articles to the Author

Analysing literature gives an overview of the “WHs”: WHat has been reported in a particular field or topic, WHo the key writers are, WHat are the prevailing theories and hypotheses, WHat questions are being asked (and answered), and WHat methods and methodologies are appropriate and useful [ 11 ]. For new or aspiring researchers in a particular field, it can be quite challenging to get a comprehensive overview of their respective fields, especially the historical trends and what has been studied previously. As such, the importance of review articles to knowledge appraisal and contribution cannot be overemphasised, which is reflected in the constant demand for such articles in the research community. However, it is also important for the author, especially the first-time author, to recognise the importance of his/her investing time and effort into writing a quality review article.

Generally, literature reviews are undertaken for many reasons, mainly for publication and for dissertation purposes. The major purpose of literature reviews is to provide direction and information for the improvement of scientific knowledge. They also form a significant component in the research process and in academic assessment [ 12 ]. There may be, however, a thin line between a dissertation literature review and a published review article, given that with some modifications, a literature review can be transformed into a legitimate and publishable scholarly document. According to Gülpınar and Güçlü [ 6 ], the basic motivation for writing a review article is to make a comprehensive synthesis of the most appropriate literature on a specific research inquiry or topic. Thus, conducting a literature review assists in demonstrating the author's knowledge about a particular field of study, which may include but not be limited to its history, theories, key variables, vocabulary, phenomena, and methodologies [ 10 ]. Furthermore, publishing reviews is beneficial as it permits the researchers to examine different questions and, as a result, enhances the depth and diversity of their scientific reasoning [ 1 ]. In addition, writing review articles allows researchers to share insights with the scientific community while identifying knowledge gaps to be addressed in future research. The review writing process can also be a useful tool in training early-career scientists in leadership, coordination, project management, and other important soft skills necessary for success in the research world [ 13 ]. Another important reason for authoring reviews is that such publications have been observed to be remarkably influential, extending the reach of an author in multiple folds of what can be achieved by primary research papers [ 1 ]. The trend in science is for authors to receive more citations from their review articles than from their original research articles. According to Miranda and Garcia-Carpintero [ 14 ], review articles are, on average, three times more frequently cited than original research articles; they also asserted that a 20% increase in review authorship could result in a 40–80% increase in citations of the author. As a result, writing reviews can significantly impact a researcher's citation output and serve as a valuable channel to reach a wider scientific audience. In addition, the references cited in a review article also provide the reader with an opportunity to dig deeper into the topic of interest. Thus, review articles can serve as a valuable repository for consultation, increasing the visibility of the authors and resulting in more citations.

3. Types of Review Articles

The first step in writing a good literature review is to decide on the particular type of review to be written; hence, it is important to distinguish and understand the various types of review articles. Although scientific review articles have been classified according to various schemes, however, they are broadly categorised into narrative reviews, systematic reviews, and meta-analyses [ 15 ]. It was observed that more authors—as well as publishers—were leaning towards systematic reviews and meta-analysis while downplaying narrative reviews; however, the three serve different aims and should all be considered equally important in science [ 1 ]. Bibliometric reviews and patent reviews, which are closely related to meta-analysis, have also gained significant attention recently. However, from another angle, a review could also be of two types. In the first class, authors could deal with a widely studied topic where there is already an accumulated body of knowledge that requires analysis and synthesis [ 3 ]. At the other end of the spectrum, the authors may have to address an emerging issue that would benefit from exposure to potential theoretical foundations; hence, their contribution would arise from the fresh theoretical foundations proposed in developing a conceptual model [ 3 ].

3.1. Narrative Reviews

Narrative reviewers are mainly focused on providing clarification and critical analysis on a particular topic or body of literature through interpretative synthesis, creativity, and expert judgement. According to Green et al. [ 16 ], a narrative review can be in the form of editorials, commentaries, and narrative overviews. However, editorials and commentaries are usually expert opinions; hence, a beginner is more likely to write a narrative overview, which is more general and is also referred to as an unsystematic narrative review. Similarly, the literature review section of most dissertations and empirical papers is typically narrative in nature. Typically, narrative reviews combine results from studies that may have different methodologies to address different questions or to formulate a broad theoretical formulation [ 1 ]. They are largely integrative as strong focus is placed on the assimilation and synthesis of various aspects in the review, which may involve comparing and contrasting research findings or deriving structured implications [ 17 ]. In addition, they are also qualitative studies because they do not follow strict selection processes; hence, choosing publications is relatively more subjective and unsystematic [ 18 ]. However, despite their popularity, there are concerns about their inherent subjectivity. In many instances, when the supporting data for narrative reviews are examined more closely, the evaluations provided by the author(s) become quite questionable [ 19 ]. Nevertheless, if the goal of the author is to formulate a new theory that connects diverse strands of research, a narrative method is most appropriate.

3.2. Systematic Reviews

In contrast to narrative reviews, which are generally descriptive, systematic reviews employ a systematic approach to summarise evidence on research questions. Hence, systematic reviews make use of precise and rigorous criteria to identify, evaluate, and subsequently synthesise all relevant literature on a particular topic [ 12 , 20 ]. As a result, systematic reviews are more likely to inspire research ideas by identifying knowledge gaps or inconsistencies, thus helping the researcher to clearly define the research hypotheses or questions [ 21 ]. Furthermore, systematic reviews may serve as independent research projects in their own right, as they follow a defined methodology to search and combine reliable results to synthesise a new database that can be used for a variety of purposes [ 22 ]. Typically, the peculiarities of the individual reviewer, different search engines, and information databases used all ensure that no two searches will yield the same systematic results even if the searches are conducted simultaneously and under identical criteria [ 11 ]. Hence, attempts are made at standardising the exercise via specific methods that would limit bias and chance effects, prevent duplications, and provide more accurate results upon which conclusions and decisions can be made.

The most established of these methods is the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines which objectively defined statements, guidelines, reporting checklists, and flowcharts for undertaking systematic reviews as well as meta-analysis [ 23 ]. Though mainly designed for research in medical sciences, the PRISMA approach has gained wide acceptance in other fields of science and is based on eight fundamental propositions. These include the explicit definition of the review question, an unambiguous outline of the study protocol, an objective and exhaustive systematic review of reputable literature, and an unambiguous identification of included literature based on defined selection criteria [ 24 ]. Other considerations include an unbiased appraisal of the quality of the selected studies (literature), organic synthesis of the evidence of the study, preparation of the manuscript based on the reporting guidelines, and periodic update of the review as new data emerge [ 24 ]. Other methods such as PRISMA-P (Preferred Reporting Items for Systematic review and Meta-Analysis Protocols), MOOSE (Meta-analysis Of Observational Studies in Epidemiology), and ROSES (Reporting Standards for Systematic Evidence Syntheses) have since been developed for systematic reviews (and meta-analysis), with most of them being derived from PRISMA.

Consequently, systematic reviews—unlike narrative reviews—must contain a methodology section which in addition to all that was highlighted above must fully describe the precise criteria used in formulating the research question and setting the inclusion or exclusion criteria used in selecting/accessing the literature. Similarly, the criteria for evaluating the quality of the literature included in the review as well as for analysing, synthesising, and disseminating the findings must be fully described in the methodology section.

3.3. Meta-Analysis

Meta-analyses are considered as more specialised forms of systematic reviews. Generally, they combine the results of many studies that use similar or closely related methods to address the same question or share a common quantitative evaluation method [ 25 ]. However, meta-analyses are also a step higher than other systematic reviews as they are focused on numerical data and involve the use of statistics in evaluating different studies and synthesising new knowledge. The major advantage of this type of review is the increased statistical power leading to more reliable results for inferring modest associations and a more comprehensive understanding of the true impact of a research study [ 26 ]. Unlike in traditional systematic reviews, research topics covered in meta-analyses must be mature enough to allow the inclusion of sufficient homogeneous empirical research in terms of subjects, interventions, and outcomes [ 27 , 28 ].

Being an advanced form of systematic review, meta-analyses must also have a distinct methodology section; hence, the standard procedures involved in the traditional systematic review (especially PRISMA) also apply in meta-analyses [ 23 ]. In addition to the common steps in formulating systematic reviews, meta-analyses are required to describe how nested and missing data are handled, the effect observed in each study, the confidence interval associated with each synthesised effect, and any potential for bias presented within the sample(s) [ 17 ]. According to Paul and Barari [ 28 ], a meta-analysis must also detail the final sample, the meta-analytic model, and the overall analysis, moderator analysis, and software employed. While the overall analysis involves the statistical characterization of the relationships between variables in the meta-analytic framework and their significance, the moderator analysis defines the different variables that may affect variations in the original studies [ 28 , 29 ]. It must also be noted that the accuracy and reliability of meta-analyses have both been significantly enhanced by the incorporation of statistical approaches such as Bayesian analysis [ 30 ], network analysis [ 31 ], and more recently, machine learning [ 32 ].

3.4. Bibliometric Review

A bibliometric review, commonly referred to as bibliometric analysis, is a systematic evaluation of published works within a specific field or discipline [ 33 ]. This bibliometric methodology involves the use of quantitative methods to analyse bibliometric data such as the characteristics and numbers of publications, units of citations, authorship, co-authorship, and journal impact factors [ 34 ]. Academics use bibliometric analysis with different objectives in mind, which includes uncovering emerging trends in article and journal performance, elaborating collaboration patterns and research constituents, evaluating the impact and influence of particular authors, publications, or research groups, and highlighting the intellectual framework of a certain field [ 35 ]. It is also used to inform policy and decision-making. Similarly to meta-analysis, bibliometric reviews rely upon quantitative techniques, thus avoiding the interpretation bias that could arise from the qualitative techniques of other types of reviews [ 36 ]. However, while bibliometric analysis synthesises the bibliometric and intellectual structure of a field by examining the social and structural linkages between various research parts, meta-analysis focuses on summarising empirical evidence by probing the direction and strength of effects and relationships among variables, especially in open research questions [ 37 , 38 ]. However, similarly to systematic review and meta-analysis, a bibliometric review also requires a well-detailed methodology section. The amount of data to be analysed in bibliometric analysis is quite massive, running to hundreds and tens of thousands in some cases. Although the data are objective in nature (e.g., number of citations and publications and occurrences of keywords and topics), the interpretation is usually carried out through both objective (e.g., performance analysis) and subjective (e.g., thematic analysis) evaluations [ 35 ]. However, the invention and availability of bibliometric software such as BibExcel, Gephi, Leximancer, and VOSviewer and scientific databases such as Dimensions, Web of Science, and Scopus have made this type of analysis more feasible.

3.5. Patent Review

Patent reviews provide a comprehensive analysis and critique of a specific patent or a group of related patents, thus presenting a concise understanding of the technology or innovation that is covered by the patent [ 39 ]. This type of article is useful for researchers as it also enhances their understanding of the legal, technical, and commercial aspects of an intellectual property/innovation; in addition, it is also important for stakeholders outside the research community including IP (intellectual property) specialists, legal professionals, and technology-transfer officers [ 40 ]. Typically, patent reviews encompass the scope, background, claims, legal implications, technical specifications, and potential commercial applications of the patent(s). The article may also include a discussion of the patent's strengths and weaknesses, as well as its potential impact on the industry or field in which it operates. Most times, reviews are time specified, they may be regionalised, and the data are usually retrieved via patent searches on databases such as that of the European Patent Office ( https://www.epo.org/searching.html ), United States Patent and Trademark Office ( https://patft.uspto.gov/ ), the World Intellectual Property Organization's PATENTSCOPE ( https://patentscope.wipo.int/search/en/structuredSearch.jsf ), Google Patent ( https://www.google.com/?tbm=pts ), and China National Intellectual Property Administration ( https://pss-system.cponline.cnipa.gov.cn/conventionalSearch ). According to Cerimi et al. [ 41 ], the retrieved data and analysed may include the patent number, patent status, filing date, application date, grant dates, inventor, assignee, and pending applications. While data analysis is usually carried out by general data software such as Microsoft Excel, an intelligence software solely dedicated to patent research and analysis, Orbit Intelligence has been found to be more efficient [ 39 ]. It is also mandatory to include a methodology section in a patent review, and this should be explicit, thorough, and precise to allow a clear understanding of how the analysis was carried out and how the conclusions were arrived at.

4. Searching Literature

One of the most challenging tasks in writing a review article on a subject is the search for relevant literature to populate the manuscript as the author is required to garner information from an endless number of sources. This is even more challenging as research outputs have been increasing astronomically, especially in the last decade, with thousands of new articles published annually in various fields. It is therefore imperative that the author must not only be aware of the overall trajectory in a field of investigation but must also be cognizant of recent studies so as not to publish outdated research or review articles. Basically, the search for the literature involves a coherent conceptual structuring of the topic itself and a thorough collation of evidence under the common themes which might reflect the histories, conflicts, standoffs, revolutions, and/or evolutions in the field [ 7 ]. To start the search process, the author must carefully identify and select broad keywords relevant to the subject; subsequently, the keywords should be developed to refine the search into specific subheadings that would facilitate the structure of the review.

Two main tactics have been identified for searching the literature, namely, systematic and snowballing [ 42 ]. The systematic approach involves searching literature with specific keywords (for example, cancer, antioxidant, and nanoparticles), which leads to an almost unmanageable and overwhelming list of possible sources [ 43 ]. The snowballing approach, however, involves the identification of a particular publication, followed by the compilation of a bibliography of articles based on the reference list of the identified publication [ 44 ]. Many times, it might be necessary to combine both approaches, but irrespective, the author must keep an accurate track and record of papers cited in the search. A simple and efficient strategy for populating the bibliography of review articles is to go through the abstract (and sometimes the conclusion) of a paper; if the abstract is related to the topic of discourse, the author might go ahead and read the entire article; otherwise, he/she is advised to move on [ 45 ]. Winchester and Salji [ 5 ] noted that to learn the background of the subject/topic to be reviewed, starting literature searches with academic textbooks or published review articles is imperative, especially for beginners. Furthermore, it would also assist in compiling the list of keywords, identifying areas of further exploration, and providing a glimpse of the current state of the research. However, past reviews ideally are not to serve as the foundation of a new review as they are written from someone else's viewpoint, which might have been tainted with some bias. Fortunately, the accessibility and search for the literature have been made relatively easier than they were a few decades ago as the current information age has placed an enormous volume of knowledge right at our fingertips [ 46 ]. Nevertheless, when gathering the literature from the Internet, authors should exercise utmost caution as much of the information may not be verified or peer-reviewed and thus may be unregulated and unreliable. For instance, Wikipedia, despite being a large repository of information with more than 6.7 million articles in the English language alone, is considered unreliable for scientific literature reviews, due to its openness to public editing [ 47 ]. However, in addition to peer-reviewed journal publications—which are most ideal—reviews can also be drawn from a wide range of other sources such as technical documents, in-house reports, conference abstracts, and conference proceedings. Similarly, “Google Scholar”—as against “Google” and other general search engines—is more appropriate as its searches are restricted to only academic articles produced by scholarly societies or/and publishers [ 48 ]. Furthermore, the various electronic databases, such as ScienceDirect, Web of Science, PubMed, and MEDLINE, many of which focus on specific fields of research, are also ideal options [ 49 ]. Advancement in computer indexing has remarkably expanded the ease and ability to search large databases for every potentially relevant article. In addition to searching by topic, literature search can be modified by time; however, there must be a balance between old papers and recent ones. The general consensus in science is that publications less than five years old are considered recent.

It is important, especially in systematic reviews and meta-analyses, that the specific method of running the computer searches be properly documented as there is the need to include this in the method (methodology) section of such papers. Typically, the method details the keywords, databases explored, search terms used, and the inclusion/exclusion criteria applied in the selection of data and any other specific decision/criteria. All of these will ensure the reproducibility and thoroughness of the search and the selection procedure. However, Randolph [ 10 ] noted that Internet searches might not give the exhaustive list of articles needed for a review article; hence, it is advised that authors search through the reference lists of articles that were obtained initially from the Internet search. After determining the relevant articles from the list, the author should read through the references of these articles and repeat the cycle until saturation is reached [ 10 ]. After populating the articles needed for the literature review, the next step is to analyse them individually and in their whole entirety. A systematic approach to this is to identify the key information within the papers, examine them in depth, and synthesise original perspectives by integrating the information and making inferences based on the findings. In this regard, it is imperative to link one source to the other in a logical manner, for instance, taking note of studies with similar methodologies, papers that agree, or results that are contradictory [ 42 ].

5. Structuring the Review Article

The title and abstract are the main selling points of a review article, as most readers will only peruse these two elements and usually go on to read the full paper if they are drawn in by either or both of the two. Tullu [ 50 ] recommends that the title of a scientific paper “should be descriptive, direct, accurate, appropriate, interesting, concise, precise, unique, and not be misleading.” In addition to providing “just enough details” to entice the reader, words in the titles are also used by electronic databases, journal websites, and search engines to index and retrieve a particular paper during a search [ 51 ]. Titles are of different types and must be chosen according to the topic under review. They are generally classified as descriptive, declarative, or interrogative and can also be grouped into compound, nominal, or full-sentence titles [ 50 ]. The subject of these categorisations has been extensively discussed in many articles; however, the reader must also be aware of the compound titles, which usually contain a main title and a subtitle. Typically, subtitles provide additional context—to the main title—and they may specify the geographic scope of the research, research methodology, or sample size [ 52 ].

Just like primary research articles, there are many debates about the optimum length of a review article's title. However, the general consensus is to keep the title as brief as possible while not being too general. A title length between 10 and 15 words is recommended, since longer titles can be more challenging to comprehend. Paiva et al. [ 53 ] observed that articles which contain 95 characters or less get more views and citations. However, emphasis must be placed on conciseness as the audience will be more satisfied if they can understand what exactly the review has contributed to the field, rather than just a hint about the general topic area. Authors should also endeavour to stick to the journal's specific requirements, especially regarding the length of the title and what they should or should not contain [ 9 ]. Thus, avoidance of filler words such as “a review on/of,” “an observation of,” or “a study of” is a very simple way to limit title length. In addition, abbreviations or acronyms should be avoided in the title, except the standard or commonly interpreted ones such as AIDS, DNA, HIV, and RNA. In summary, to write an effective title, the authors should consider the following points. What is the paper about? What was the methodology used? What were the highlights and major conclusions? Subsequently, the author should list all the keywords from these answers, construct a sentence from these keywords, and finally delete all redundant words from the sentence title. It is also possible to gain some ideas by scanning indices and article titles in major journals in the field. It is important to emphasise that a title is not chosen and set in stone, and the title is most likely to be continually revised and adjusted until the end of the writing process.

5.2. Abstract

The abstract, also referred to as the synopsis, is a summary of the full research paper; it is typically independent and can stand alone. For most readers, a publication does not exist beyond the abstract, partly because abstracts are often the only section of a paper that is made available to the readers at no cost, whereas the full paper may attract a payment or subscription [ 54 ]. Thus, the abstract is supposed to set the tone for the few readers who wish to read the rest of the paper. It has also been noted that the abstract gives the first impression of a research work to journal editors, conference scientific committees, or referees, who might outright reject the paper if the abstract is poorly written or inadequate [ 50 ]. Hence, it is imperative that the abstract succinctly represents the entire paper and projects it positively. Just like the title, abstracts have to be balanced, comprehensive, concise, functional, independent, precise, scholarly, and unbiased and not be misleading [ 55 ]. Basically, the abstract should be formulated using keywords from all the sections of the main manuscript. Thus, it is pertinent that the abstract conveys the focus, key message, rationale, and novelty of the paper without any compromise or exaggeration. Furthermore, the abstract must be consistent with the rest of the paper; as basic as this instruction might sound, it is not to be taken for granted. For example, a study by Vrijhoef and Steuten [ 56 ] revealed that 18–68% of 264 abstracts from some scientific journals contained information that was inconsistent with the main body of the publications.

Abstracts can either be structured or unstructured; in addition, they can further be classified as either descriptive or informative. Unstructured abstracts, which are used by many scientific journals, are free flowing with no predefined subheadings, while structured abstracts have specific subheadings/subsections under which the abstract needs to be composed. Structured abstracts have been noted to be more informative and are usually divided into subsections which include the study background/introduction, objectives, methodology design, results, and conclusions [ 57 ]. No matter the style chosen, the author must carefully conform to the instructions provided by the potential journal of submission, which may include but are not limited to the format, font size/style, word limit, and subheadings [ 58 ]. The word limit for abstracts in most scientific journals is typically between 150 and 300 words. It is also a general rule that abstracts do not contain any references whatsoever.

Typically, an abstract should be written in the active voice, and there is no such thing as a perfect abstract as it could always be improved on. It is advised that the author first makes an initial draft which would contain all the essential parts of the paper, which could then be polished subsequently. The draft should begin with a brief background which would lead to the research questions. It might also include a general overview of the methodology used (if applicable) and importantly, the major results/observations/highlights of the review paper. The abstract should end with one or few sentences about any implications, perspectives, or future research that may be developed from the review exercise. Finally, the authors should eliminate redundant words and edit the abstract to the correct word count permitted by the journal [ 59 ]. It is always beneficial to read previous abstracts published in the intended journal, related topics/subjects from other journals, and other reputable sources. Furthermore, the author should endeavour to get feedback on the abstract especially from peers and co-authors. As the abstract is the face of the whole paper, it is best that it is the last section to be finalised, as by this time, the author would have developed a clearer understanding of the findings and conclusions of the entire paper.

5.3. Graphical Abstracts

Since the mid-2000s, an increasing number of journals now require authors to provide a graphical abstract (GA) in addition to the traditional written abstract, to increase the accessibility of scientific publications to readers [ 60 ]. A study showed that publications with GA performed better than those without it, when the abstract views, total citations, and downloads were compared [ 61 ]. However, the GA should provide “a single, concise pictorial, and visual summary of the main findings of an article” [ 62 ]. Although they are meant to be a stand-alone summary of the whole paper, it has been noted that they are not so easily comprehensible without having read through the traditionally written abstract [ 63 ]. It is important to note that, like traditional abstracts, many reputable journals require GAs to adhere to certain specifications such as colour, dimension, quality, file size, and file format (usually JPEG/JPG, PDF, PNG, or TIFF). In addition, it is imperative to use engaging and accurate figures, all of which must be synthesised in order to accurately reflect the key message of the paper. Currently, there are various online or downloadable graphical tools that can be used for creating GAs, such as Microsoft Paint or PowerPoint, Mindthegraph, ChemDraw, CorelDraw, and BioRender.

5.4. Keywords

As a standard practice, journals require authors to select 4–8 keywords (or phrases), which are typically listed below the abstract. A good set of keywords will enable indexers and search engines to find relevant papers more easily and can be considered as a very concise abstract [ 64 ]. According to Dewan and Gupta [ 51 ], the selection of appropriate keywords will significantly enhance the retrieval, accession, and consequently, the citation of the review paper. Ideally, keywords can be variants of the terms/phrases used in the title, the abstract, and the main text, but they should ideally not be the exact words in the main title. Choosing the most appropriate keywords for a review article involves listing down the key terms and phrases in the article, including abbreviations. Subsequently, a quick review of the glossary/vocabulary/term list or indexing standard in the specific discipline will assist in selecting the best and most precise keywords that match those used in the databases from the list drawn. In addition, the keywords should not be broad or general terms (e.g., DNA, biology, and enzymes) but must be specific to the field or subfield of study as well as to the particular paper [ 65 ].

5.5. Introduction

The introduction of an article is the first major section of the manuscript, and it presents basic information to the reader without compelling them to study past publications. In addition, the introduction directs the reader to the main arguments and points developed in the main body of the article while clarifying the current state of knowledge in that particular area of research [ 12 ]. The introduction part of a review article is usually sectionalised into background information, a description of the main topic and finally a statement of the main purpose of the review [ 66 ]. Authors may begin the introduction with brief general statements—which provide background knowledge on the subject matter—that lead to more specific ones [ 67 ]. It is at this point that the reader's attention must be caught as the background knowledge must highlight the importance and justification for the subject being discussed, while also identifying the major problem to be addressed [ 68 ]. In addition, the background should be broad enough to attract even nonspecialists in the field to maximise the impact and widen the reach of the article. All of these should be done in the light of current literature; however, old references may also be used for historical purposes. A very important aspect of the introduction is clearly stating and establishing the research problem(s) and how a review of the particular topic contributes to those problem(s). Thus, the research gap which the paper intends to fill, the limitations of previous works and past reviews, if available, and the new knowledge to be contributed must all be highlighted. Inadequate information and the inability to clarify the problem will keep readers (who have the desire to obtain new information) from reading beyond the introduction [ 69 ]. It is also pertinent that the author establishes the purpose of reviewing the literature and defines the scope as well as the major synthesised point of view. Furthermore, a brief insight into the criteria used to select, evaluate, and analyse the literature, as well as the outline or sequence of the review, should be provided in the introduction. Subsequently, the specific objectives of the review article must be presented. The last part of the “introduction” section should focus on the solution, the way forward, the recommendations, and the further areas of research as deduced from the whole review process. According to DeMaria [ 70 ], clearly expressed or recommended solutions to an explicitly revealed problem are very important for the wholesomeness of the “introduction” section. It is believed that following these steps will give readers the opportunity to track the problems and the corresponding solution from their own perspective in the light of current literature. As against some suggestions that the introduction should be written only in present tenses, it is also believed that it could be done with other tenses in addition to the present tense. In this regard, general facts should be written in the present tense, specific research/work should be in the past tense, while the concluding statement should be in the past perfect or simple past. Furthermore, many of the abbreviations to be used in the rest of the manuscript and their explanations should be defined in this section.

5.6. Methodology

Writing a review article is equivalent to conducting a research study, with the information gathered by the author (reviewer) representing the data. Like all major studies, it involves conceptualisation, planning, implementation, and dissemination [ 71 ], all of which may be detailed in a methodology section, if necessary. Hence, the methodological section of a review paper (which can also be referred to as the review protocol) details how the relevant literature was selected and how it was analysed as well as summarised. The selection details may include, but are not limited to, the database consulted and the specific search terms used together with the inclusion/exclusion criteria. As earlier highlighted in Section 3 , a description of the methodology is required for all types of reviews except for narrative reviews. This is partly because unlike narrative reviews, all other review articles follow systematic approaches which must ensure significant reproducibility [ 72 ]. Therefore, where necessary, the methods of data extraction from the literature and data synthesis must also be highlighted as well. In some cases, it is important to show how data were combined by highlighting the statistical methods used, measures of effect, and tests performed, as well as demonstrating heterogeneity and publication bias [ 73 ].

The methodology should also detail the major databases consulted during the literature search, e.g., Dimensions, ScienceDirect, Web of Science, MEDLINE, and PubMed. For meta-analysis, it is imperative to highlight the software and/or package used, which could include Comprehensive Meta-Analysis, OpenMEE, Review Manager (RevMan), Stata, SAS, and R Studio. It is also necessary to state the mathematical methods used for the analysis; examples of these include the Bayesian analysis, the Mantel–Haenszel method, and the inverse variance method. The methodology should also state the number of authors that carried out the initial review stage of the study, as it has been recommended that at least two reviews should be done blindly and in parallel, especially when it comes to the acquisition and synthesis of data [ 74 ]. Finally, the quality and validity assessment of the publication used in the review must be stated and well clarified [ 73 ].

5.7. Main Body of the Review

Ideally, the main body of a publishable review should answer these questions: What is new (contribution)? Why so (logic)? So what (impact)? How well it is done (thoroughness)? The flow of the main body of a review article must be well organised to adequately maintain the attention of the readers as well as guide them through the section. It is recommended that the author should consider drawing a conceptual scheme of the main body first, using methods such as mind-mapping. This will help create a logical flow of thought and presentation, while also linking the various sections of the manuscript together. According to Moreira [ 75 ], “reports do not simply yield their findings, rather reviewers make them yield,” and thus, it is the author's responsibility to transform “resistant” texts into “docile” texts. Hence, after the search for the literature, the essential themes and key concepts of the review paper must be identified and synthesised together. This synthesis primarily involves creating hypotheses about the relationships between the concepts with the aim of increasing the understanding of the topic being reviewed. The important information from the various sources should not only be summarised, but the significance of studies must be related back to the initial question(s) posed by the review article. Furthermore, MacLure [ 76 ] stated that data are not just to be plainly “extracted intact” and “used exactly as extracted,” but must be modified, reconfigured, transformed, transposed, converted, tabulated, graphed, or manipulated to enable synthesis, combination, and comparison. Therefore, different pieces of information must be extracted from the reports in which they were previously deposited and then refined into the body of the new article [ 75 ]. To this end, adequate comparison and combination might require that “qualitative data be quantified” or/and “quantitative data may be qualitized” [ 77 ]. In order to accomplish all of these goals, the author may have to transform, paraphrase, generalize, specify, and reorder the text [ 78 ]. For comprehensiveness, the body paragraphs should be arranged in a similar order as it was initially stated in the abstract or/and introduction. Thus, the main body could be divided into thematic areas, each of which could be independently comprehensive and treated as a mini review. Similarly, the sections can also be arranged chronologically depending on the focus of the review. Furthermore, the abstractions should proceed from a wider general view of the literature being reviewed and then be narrowed down to the specifics. In the process, deep insights should also be provided between the topic of the review and the wider subject area, e.g., fungal enzymes and enzymes in general. The abstractions must also be discussed in more detail by presenting more specific information from the identified sources (with proper citations of course!). For example, it is important to identify and highlight contrary findings and rival interpretations as well as to point out areas of agreement or debate among different bodies of literature. Often, there are previous reviews on the same topic/concept; however, this does not prevent a new author from writing one on the same topic, especially if the previous reviews were written many years ago. However, it is important that the body of the new manuscript be written from a new angle that was not adequately covered in the past reviews and should also incorporate new studies that have accumulated since the last review(s). In addition, the new review might also highlight the approaches, limitations, and conclusions of the past studies. But the authors must not be excessively critical of the past reviews as this is regarded by many authors as a sign of poor professionalism [ 3 , 79 ]. Daft [ 79 ] emphasized that it is more important for a reviewer to state how their research builds on previous work instead of outright claiming that previous works are incompetent and inadequate. However, if a series of related papers on one topic have a common error or research flaw that needs rectification, the reviewer must point this out with the aim of moving the field forward [ 3 ]. Like every other scientific paper, the main body of a review article also needs to be consistent in style, for example, in the choice of passive vs. active voice and present vs. past tense. It is also important to note that tables and figures can serve as a powerful tool for highlighting key points in the body of the review, and they are now considered core elements of reviews. For more guidance and insights into what should make up the contents of a good review article, readers are also advised to get familiarised with the Boote and Beile [ 80 ] literature review scoring rubric as well as the review article checklist of Short [ 81 ].

5.8. Tables and Figures

An ideal review article should be logically structured and efficiently utilise illustrations, in the form of tables and figures, to convey the key findings and relationships in the study. According to Tay [ 13 ], illustrations often take a secondary role in review papers when compared to primary research papers which are focused on illustrations. However, illustrations are very important in review articles as they can serve as succinct means of communicating major findings and insights. Franzblau and Chung [ 82 ] pointed out that illustrations serve three major purposes in a scientific article: they simplify complex data and relationships for better understanding, they minimise reading time by summarising and bringing to focus on the key findings (or trends), and last, they help to reduce the overall word count. Hence, inserting and constructing illustrations in a review article is as meticulous as it is important. However, important decisions should be made on whether the charts, figures, or tables to be potentially inserted in the manuscript are indeed needed and how best to design them [ 83 ]. Illustrations should enhance the text while providing necessary information; thus, the information described in illustrations should not contradict that in the main text and should also not be a repetition of texts [ 84 ]. Furthermore, illustrations must be autonomous, meaning they ought to be intelligible without having to read the text portion of the manuscript; thus, the reader does not have to flip back and forth between the illustration and the main text in order to understand it [ 85 ]. It should be noted that tables or figures that directly reiterate the main text or contain extraneous information will only make a mess of the manuscript and discourage readers [ 86 ].

Kotz and Cals [ 87 ] recommend that the layout of tables and figures should be carefully designed in a clear manner with suitable layouts, which will allow them to be referred to logically and chronologically in the text. In addition, illustrations should only contain simple text, as lengthy details would contradict their initial objective, which was to provide simple examples or an overview. Furthermore, the use of abbreviations in illustrations, especially tables, should be avoided if possible. If not, the abbreviations should be defined explicitly in the footnotes or legends of the illustration [ 88 ]. Similarly, numerical values in tables and graphs should also be correctly approximated [ 84 ]. It is recommended that the number of tables and figures in the manuscript should not exceed the target journal's specification. According to Saver [ 89 ], they ideally should not account for more than one-third of the manuscript. Finally, the author(s) must seek permission and give credits for using an already published illustration when necessary. However, none of these are needed if the graphic is originally created by the author, but if it is a reproduced or an adapted illustration, the author must obtain permission from the copyright owner and include the necessary credit. One of the very important tools for designing illustrations is Creative Commons, a platform that provides a wide range of creative works which are available to the public for use and modification.

5.9. Conclusion/Future Perspectives

It has been observed that many reviews end abruptly with a short conclusion; however, a lot more can be included in this section in addition to what has been said in the major sections of the paper. Basically, the conclusion section of a review article should provide a summary of key findings from the main body of the manuscript. In this section, the author needs to revisit the critical points of the paper as well as highlight the accuracy, validity, and relevance of the inferences drawn in the article review. A good conclusion should highlight the relationship between the major points and the author's hypothesis as well as the relationship between the hypothesis and the broader discussion to demonstrate the significance of the review article in a larger context. In addition to giving a concise summary of the important findings that describe current knowledge, the conclusion must also offer a rationale for conducting future research [ 12 ]. Knowledge gaps should be identified, and themes should be logically developed in order to construct conceptual frameworks as well as present a way forward for future research in the field of study [ 11 ].

Furthermore, the author may have to justify the propositions made earlier in the manuscript, demonstrate how the paper extends past research works, and also suggest ways that the expounded theories can be empirically examined [ 3 ]. Unlike experimental studies which can only draw either a positive conclusion or ambiguous failure to reject the null hypothesis, four possible conclusions can be drawn from review articles [ 1 ]. First, the theory/hypothesis propounded may be correct after being proven from current evidence; second, the hypothesis may not be explicitly proven but is most probably the best guess. The third conclusion is that the currently available evidence does not permit a confident conclusion or a best guess, while the last conclusion is that the theory or hypothesis is false [ 1 ]. It is important not to present new information in the conclusion section which has link whatsoever with the rest of the manuscript. According to Harris et al. [ 90 ], the conclusions should, in essence, answer the question: if a reader were to remember one thing about the review, what would it be?

5.10. References

As it has been noted in different parts of this paper, authors must give the required credit to any work or source(s) of information that was included in the review article. This must include the in-text citations in the main body of the paper and the corresponding entries in the reference list. Ideally, this full bibliographical list is the last part of the review article, and it should contain all the books, book chapters, journal articles, reports, and other media, which were utilised in the manuscript. It has been noted that most journals and publishers have their own specific referencing styles which are all derived from the more popular styles such as the American Psychological Association (APA), Chicago, Harvard, Modern Language Association (MLA), and Vancouver styles. However, all these styles may be categorised into either the parenthetical or numerical referencing style. Although a few journals do not have strict referencing rules, it is the responsibility of the author to reference according to the style and instructions of the journal. Omissions and errors must be avoided at all costs, and this can be easily achieved by going over the references many times for due diligence [ 11 ]. According to Cronin et al. [ 12 ], a separate file for references can be created, and any work used in the manuscript can be added to this list immediately after being cited in the text [ 12 ]. In recent times, the emergence of various referencing management software applications such as Endnote, RefWorks, Mendeley, and Zotero has even made referencing easier. The majority of these software applications require little technical expertise, and many of them are free to use, while others may require a subscription. It is imperative, however, that even after using these software packages, the author must manually curate the references during the final draft, in order to avoid any errors, since these programs are not impervious to errors, particularly formatting errors.

6. Concluding Remarks

Writing a review article is a skill that needs to be learned; it is a rigorous but rewarding endeavour as it can provide a useful platform to project the emerging researcher or postgraduate student into the gratifying world of publishing. Thus, the reviewer must develop the ability to think critically, spot patterns in a large volume of information, and must be invested in writing without tiring. The prospective author must also be inspired and dedicated to the successful completion of the article while also ensuring that the review article is not just a mere list or summary of previous research. It is also important that the review process must be focused on the literature and not on the authors; thus, overt criticism of existing research and personal aspersions must be avoided at all costs. All ideas, sentences, words, and illustrations should be constructed in a way to avoid plagiarism; basically, this can be achieved by paraphrasing, summarising, and giving the necessary acknowledgments. Currently, there are many tools to track and detect plagiarism in manuscripts, ensuring that they fall within a reasonable similarity index (which is typically 15% or lower for most journals). Although the more popular of these tools, such as Turnitin and iThenticate, are subscription-based, there are many freely available web-based options as well. An ideal review article is supposed to motivate the research topic and describe its key concepts while delineating the boundaries of research. In this regard, experience-based information on how to methodologically develop acceptable and impactful review articles has been detailed in this paper. Furthermore, for a beginner, this guide has detailed “the why” and “the how” of authoring a good scientific review article. However, the information in this paper may as a whole or in parts be also applicable to other fields of research and to other writing endeavours such as writing literature review in theses, dissertations, and primary research articles. Finally, the intending authors must put all the basic rules of scientific writing and writing in general into cognizance. A comprehensive study of the articles cited within this paper and other related articles focused on scientific writing will further enhance the ability of the motivated beginner to deliver a good review article.

Acknowledgments

This work was supported by the National Research Foundation of South Africa under grant number UID 138097. The authors would like to thank the Durban University of Technology for funding the postdoctoral fellowship of the first author, Dr. Ayodeji Amobonye.

Data Availability

Conflicts of interest.

The authors declare that they have no conflicts of interest.

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• What Is Peer Review? | Types & Examples

What Is Peer Review? | Types & Examples

Published on 6 May 2022 by Tegan George . Revised on 2 September 2022.

Peer review, sometimes referred to as refereeing , is the process of evaluating submissions to an academic journal. Using strict criteria, a panel of reviewers in the same subject area decides whether to accept each submission for publication.

Peer-reviewed articles are considered a highly credible source due to the stringent process they go through before publication.

There are various types of peer review. The main difference between them is to what extent the authors, reviewers, and editors know each other’s identities. The most common types are:

• Single-blind review
• Double-blind review
• Triple-blind review

Collaborative review

Open review.

Relatedly, peer assessment is a process where your peers provide you with feedback on something you’ve written, based on a set of criteria or benchmarks from an instructor. They then give constructive feedback, compliments, or guidance to help you improve your draft.

Table of contents

What is the purpose of peer review, types of peer review, the peer review process, providing feedback to your peers, peer review example, advantages of peer review, criticisms of peer review, frequently asked questions about peer review.

Many academic fields use peer review, largely to determine whether a manuscript is suitable for publication. Peer review enhances the credibility of the manuscript. For this reason, academic journals are among the most credible sources you can refer to.

However, peer review is also common in non-academic settings. The United Nations, the European Union, and many individual nations use peer review to evaluate grant applications. It is also widely used in medical and health-related fields as a teaching or quality-of-care measure.

Peer assessment is often used in the classroom as a pedagogical tool. Both receiving feedback and providing it are thought to enhance the learning process, helping students think critically and collaboratively.

Prevent plagiarism, run a free check.

Depending on the journal, there are several types of peer review.

Single-blind peer review

The most common type of peer review is single-blind (or single anonymised) review . Here, the names of the reviewers are not known by the author.

While this gives the reviewers the ability to give feedback without the possibility of interference from the author, there has been substantial criticism of this method in the last few years. Many argue that single-blind reviewing can lead to poaching or intellectual theft or that anonymised comments cause reviewers to be too harsh.

Double-blind peer review

In double-blind (or double anonymised) review , both the author and the reviewers are anonymous.

Arguments for double-blind review highlight that this mitigates any risk of prejudice on the side of the reviewer, while protecting the nature of the process. In theory, it also leads to manuscripts being published on merit rather than on the reputation of the author.

Triple-blind peer review

While triple-blind (or triple anonymised) review – where the identities of the author, reviewers, and editors are all anonymised – does exist, it is difficult to carry out in practice.

Proponents of adopting triple-blind review for journal submissions argue that it minimises potential conflicts of interest and biases. However, ensuring anonymity is logistically challenging, and current editing software is not always able to fully anonymise everyone involved in the process.

In collaborative review , authors and reviewers interact with each other directly throughout the process. However, the identity of the reviewer is not known to the author. This gives all parties the opportunity to resolve any inconsistencies or contradictions in real time, and provides them a rich forum for discussion. It can mitigate the need for multiple rounds of editing and minimise back-and-forth.

Collaborative review can be time- and resource-intensive for the journal, however. For these collaborations to occur, there has to be a set system in place, often a technological platform, with staff monitoring and fixing any bugs or glitches.

Lastly, in open review , all parties know each other’s identities throughout the process. Often, open review can also include feedback from a larger audience, such as an online forum, or reviewer feedback included as part of the final published product.

While many argue that greater transparency prevents plagiarism or unnecessary harshness, there is also concern about the quality of future scholarship if reviewers feel they have to censor their comments.

In general, the peer review process includes the following steps:

• First, the author submits the manuscript to the editor.
• Reject the manuscript and send it back to the author, or
• Send it onward to the selected peer reviewer(s)
• Next, the peer review process occurs. The reviewer provides feedback, addressing any major or minor issues with the manuscript, and gives their advice regarding what edits should be made.
• Lastly, the edited manuscript is sent back to the author. They input the edits and resubmit it to the editor for publication.

In an effort to be transparent, many journals are now disclosing who reviewed each article in the published product. There are also increasing opportunities for collaboration and feedback, with some journals allowing open communication between reviewers and authors.

It can seem daunting at first to conduct a peer review or peer assessment. If you’re not sure where to start, there are several best practices you can use.

Summarise the argument in your own words

Summarising the main argument helps the author see how their argument is interpreted by readers, and gives you a jumping-off point for providing feedback. If you’re having trouble doing this, it’s a sign that the argument needs to be clearer, more concise, or worded differently.

If the author sees that you’ve interpreted their argument differently than they intended, they have an opportunity to address any misunderstandings when they get the manuscript back.

Separate your feedback into major and minor issues

It can be challenging to keep feedback organised. One strategy is to start out with any major issues and then flow into the more minor points. It’s often helpful to keep your feedback in a numbered list, so the author has concrete points to refer back to.

Major issues typically consist of any problems with the style, flow, or key points of the manuscript. Minor issues include spelling errors, citation errors, or other smaller, easy-to-apply feedback.

The best feedback you can provide is anything that helps them strengthen their argument or resolve major stylistic issues.

Give the type of feedback that you would like to receive

No one likes being criticised, and it can be difficult to give honest feedback without sounding overly harsh or critical. One strategy you can use here is the ‘compliment sandwich’, where you ‘sandwich’ your constructive criticism between two compliments.

Be sure you are giving concrete, actionable feedback that will help the author submit a successful final draft. While you shouldn’t tell them exactly what they should do, your feedback should help them resolve any issues they may have overlooked.

As a rule of thumb, your feedback should be:

• Easy to understand
• Constructive

Below is a brief annotated research example. You can view examples of peer feedback by hovering over the highlighted sections.

Influence of phone use on sleep

Studies show that teens from the US are getting less sleep than they were a decade ago (Johnson, 2019) . On average, teens only slept for 6 hours a night in 2021, compared to 8 hours a night in 2011. Johnson mentions several potential causes, such as increased anxiety, changed diets, and increased phone use.

The current study focuses on the effect phone use before bedtime has on the number of hours of sleep teens are getting.

For this study, a sample of 300 teens was recruited using social media, such as Facebook, Instagram, and Snapchat. The first week, all teens were allowed to use their phone the way they normally would, in order to obtain a baseline.

The sample was then divided into 3 groups:

• Group 1 was not allowed to use their phone before bedtime.
• Group 2 used their phone for 1 hour before bedtime.
• Group 3 used their phone for 3 hours before bedtime.

All participants were asked to go to sleep around 10 p.m. to control for variation in bedtime . In the morning, their Fitbit showed the number of hours they’d slept. They kept track of these numbers themselves for 1 week.

Two independent t tests were used in order to compare Group 1 and Group 2, and Group 1 and Group 3. The first t test showed no significant difference ( p > .05) between the number of hours for Group 1 ( M = 7.8, SD = 0.6) and Group 2 ( M = 7.0, SD = 0.8). The second t test showed a significant difference ( p < .01) between the average difference for Group 1 ( M = 7.8, SD = 0.6) and Group 3 ( M = 6.1, SD = 1.5).

This shows that teens sleep fewer hours a night if they use their phone for over an hour before bedtime, compared to teens who use their phone for 0 to 1 hours.

Peer review is an established and hallowed process in academia, dating back hundreds of years. It provides various fields of study with metrics, expectations, and guidance to ensure published work is consistent with predetermined standards.

• Protects the quality of published research

Peer review can stop obviously problematic, falsified, or otherwise untrustworthy research from being published. Any content that raises red flags for reviewers can be closely examined in the review stage, preventing plagiarised or duplicated research from being published.

• Gives you access to feedback from experts in your field

Peer review represents an excellent opportunity to get feedback from renowned experts in your field and to improve your writing through their feedback and guidance. Experts with knowledge about your subject matter can give you feedback on both style and content, and they may also suggest avenues for further research that you hadn’t yet considered.

• Helps you identify any weaknesses in your argument

Peer review acts as a first defence, helping you ensure your argument is clear and that there are no gaps, vague terms, or unanswered questions for readers who weren’t involved in the research process. This way, you’ll end up with a more robust, more cohesive article.

While peer review is a widely accepted metric for credibility, it’s not without its drawbacks.

• Reviewer bias

The more transparent double-blind system is not yet very common, which can lead to bias in reviewing. A common criticism is that an excellent paper by a new researcher may be declined, while an objectively lower-quality submission by an established researcher would be accepted.

• Delays in publication

The thoroughness of the peer review process can lead to significant delays in publishing time. Research that was current at the time of submission may not be as current by the time it’s published.

• Risk of human error

By its very nature, peer review carries a risk of human error. In particular, falsification often cannot be detected, given that reviewers would have to replicate entire experiments to ensure the validity of results.

Peer review is a process of evaluating submissions to an academic journal. Utilising rigorous criteria, a panel of reviewers in the same subject area decide whether to accept each submission for publication.

For this reason, academic journals are often considered among the most credible sources you can use in a research project – provided that the journal itself is trustworthy and well regarded.

Peer review can stop obviously problematic, falsified, or otherwise untrustworthy research from being published. It also represents an excellent opportunity to get feedback from renowned experts in your field.

It acts as a first defence, helping you ensure your argument is clear and that there are no gaps, vague terms, or unanswered questions for readers who weren’t involved in the research process.

Peer-reviewed articles are considered a highly credible source due to this stringent process they go through before publication.

In general, the peer review process follows the following steps:

• Reject the manuscript and send it back to author, or
• Lastly, the edited manuscript is sent back to the author. They input the edits, and resubmit it to the editor for publication.

Many academic fields use peer review , largely to determine whether a manuscript is suitable for publication. Peer review enhances the credibility of the published manuscript.

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Frequently Asked Questions

What is the difference between peer-reviewed (scholarly) articles and everything else.

Peer-reviewed articles, also known as scholarly articles, are published based on the approval of a board of professional experts in the discipline relating to the article topic.

For instance, a paper discussing the psychological effects of homeschooling a child would need to be reviewed by a board of psychology scholars and professional psychologists in order to be approved for publication in a psychology journal.

Scholarly/peer-reviewed articles differ from other easily available print sources because the review process gives them more authority than, for example, a newspaper or magazine article.

Newspaper or popular magazine articles are written by journalists (not specialists in any field except journalism).

They are reviewed only by the magazine/newspaper editors (also not specialists in any field except editing).

For more information, see:  https://wrtg150.lib.byu.edu/finding-sources .

• Research and Writing

Updated 2024-03-07 14:35:37 • LibAnswers page

Peer-Reviewed Literature: Peer-Reviewed Research: Primary vs. Secondary

• Peer-Reviewed Research: Primary vs. Secondary
• Types of Peer Review
• Identifying Peer-Reviewed Research

Peer Reviewed Research

Published literature can be either peer-reviewed or non-peer-reviewed. Official research reports are almost always peer reviewed while a journal's other content is usually not. In the health sciences, official research can be primary, secondary, or even tertiary. It can be an original experiment or investigation (primary), an analysis or evaluation of primary research (secondary), or findings that compile secondary research (tertiary). If you are doing research yourself, then primary or secondary sources can reveal more in-depth information.

Primary Research

Primary research is information presented in its original form without interpretation by other researchers. While it may acknowledge previous studies or sources, it always presents original thinking, reports on discoveries, or new information about a topic.

Health sciences research that is primary includes both experimental trials and observational studies where subjects may be tested for outcomes or investigated to gain relevant insight.  Randomized Controlled Trials are the most prominent experimental design because randomized subjects offer the most compelling evidence for the effectiveness of an intervention. See the below graphic and below powerpoint for further information on primary research studies.

• Research Design

Secondary Research

Secondary research is an account of original events or facts. It is secondary to and retrospective of the actual findings from an experiment or trial. These studies may be appraised summaries, reviews, or interpretations of primary sources and often exclude the original researcher(s). In the health sciences, meta-analysis and systematic reviews are the most frequent types of secondary research. 

• A meta-analysis is a quantitative method of combining the results of primary research. In analyzing the relevant data and statistical findings from experimental trials or observational studies, it can more accurately calculate effective resolutions regarding certain health topics.
• A systematic review is a summary of research that addresses a focused clinical question in a systematic, reproducible manner. In order to provide the single best estimate of effect in clinical decision making, primary research studies are pooled together and then filtered through an inclusion/exclusion process. The relevant data and findings are then compiled and synthesized to arrive at a more accurate conclusion about a specific health topic. Only peer-reviewed publications are used and analyzed in a methodology which may or may not include a meta-analysis.

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• Insights blog

What are the different types of peer review?

There are various different types of peer review.

Peer review is the independent assessment of your research paper by experts in your field. Its purpose is to evaluate the manuscript’s quality and suitability for publication. 

Read through this guide to find out what each type means and the pros and cons. 

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Single-anonymous peer review

In this model the reviewers know that you are the author of the article, but you don’t know the identities of the reviewers. This is the most common type of peer review for science and medicine journals. 

The anonymity of the reviewers is intended to make it easier for them to give full and honest feedback on an article, without fearing that the author will hold this against them. 

Double-anonymous peer review

In this model the reviewers don’t know that you are the author of the article. And you don’t know who the reviewers are either. Double-anonymous review is particularly common in the humanities and some social sciences. 

Many researchers prefer double-anonymous review because they believe it will give their paper a fairer chance than single-anonymous review. It can avoid the risk of a paper suffering from the unintended bias of reviewers who know the seniority, gender, or nationality of a paper’s author. 

However, even if you’ve  anonymized your paper  the reviewers may not be able to avoid discerning your identity, especially if you work in a very specialized field. They might have heard you present the same ideas at a conference, or recognize your writing style. 

Find out how to make your article anonymous if you are submitting it for double-anonymous peer review. 

Open peer review

There is no one agreed definition of open peer review. In fact, a recent  study identified 122 different definitions . Typically, it will mean that the reviewers know you are the author and also that their identity will be revealed to you at some point during the review or publication process. 

Open review may also include publishing the names of the reviewers and even the reviewers’ reports alongside the article. Some open review journals also publish any earlier versions of your article, enabling the reader to see what revisions were made as a result of peer review. 

Further reading:  A new scholar’s perspective on open peer review  

Post-publication peer review

In these models, your paper may still go through one of the forms of peer review outlined above first. Alternatively, it may be published online almost immediately after some basic checks. Either way, once it is published, there will then be an opportunity for invited reviewers or even readers to add their own comments or reviews.

Registered reports

The  Registered Reports  process splits peer review into two parts. The first round of peer review takes place after you’ve designed your study but before you’ve collected or analyzed any data. This allows you to get feedback on both the question you’re looking to answer, and the experiment you’ve designed to test it. 

If your manuscript passes peer review, the journal will give you an in-principle acceptance (IPA). This indicates that your article will be published as long as you successfully complete your study according to the pre-registered methods and submit an evidence-based interpretation of the results. 

Find out about  Registered Reports at Taylor & Francis . 

Peer review with F1000Research

F1000Research  operates formally invited  post-publication peer review , which is fully open and transparent, and led by the article authors.

Reviewers are usually suggested by the authors following certain  reviewer criteria .

Peer review reports are published – alongside the reviewers’ full names and affiliations – as soon as they’re submitted and remain attached to the article if it is indexed with sites such as PubMed and Scopus.

Peer review directly determines whether an article will be indexed, via the approval status that reviewers select when reviewing the article. 

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Peer Review and Primary Literature: An Introduction: Is it Primary Research? How Do I Know?

• Scholarly Journal vs. Magazine
• Peer Review: What is it?
• Finding Peer-Reviewed Articles
• Primary Journal Literature
• Is it Primary Research? How Do I Know?

Components of a Primary Research Study

As indicated on a previous page, Peer-Reviewed Journals also include non -primary content. Simply limiting your search results in a database to "peer-reviewed" will not retrieve a list of only primary research studies.

Learn to recognize the parts of a primary research study. Terminology will vary slightly from discipline to discipline and from journal to journal.  However, there are common components to most research studies.

When you run a search, find a promising article in your results list and then look at the record for that item (usually by clicking on the title). The full database record for an item usually includes an abstract or summary--sometimes prepared by the journal or database, but often written by the author(s) themselves. This will usually give a clear indication of whether the article is a primary study.  For example, here is a full database record from a search for family violence and support in SocINDEX with Full Text :

Although the abstract often tells the story, you will need to read the article to know for sure. Besides scanning the Abstract or Summary, look for the following components: (I am only capturing small article segments for illustration.)

Look for the words METHOD or METHODOLOGY . The authors should explain how they conducted their research.

NOTE: Different Journals and Disciplines will use different terms to mean similar things. If instead of " Method " or " Methodology " you see a heading that says " Research Design " or " Data Collection ," you have a similar indicator that the scholar-authors have done original research.

Look for the section called RESULTS . This details what the author(s) found out after conducting their research.

Charts , Tables , Graphs , Maps and other displays help to summarize and present the findings of the research.

A Discussion indicates the significance of findings, acknowledges limitations of the research study, and suggests further research.

References , a Bibliography or List of Works Cited indicates a literature review and shows other studies and works that were consulted. USE THIS PART OF THE STUDY! If you find one or two good recent studies, you can identify some important earlier studies simply by going through the bibliographies of those articles.

A FINAL NOTE:  If you are ever unclear about whether a particular article is appropriate to use in your paper, it is best to show that article to your professor and discuss it with them.  The professor is the final judge since they will be assigning your grade.

Subject Guide

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Finding Journal Articles 101

Peer-reviewed or refereed.

• Research Article
• Review Article
• By Journal Title

What Does "Peer-reviewed" or "Refereed" Mean?

Peer review is a process that journals use to ensure the articles they publish represent the best scholarship currently available. When an article is submitted to a peer reviewed journal, the editors send it out to other scholars in the same field (the author's peers) to get their opinion on the quality of the scholarship, its relevance to the field, its appropriateness for the journal, etc.

Publications that don't use peer review (Time, Cosmo, Salon) just rely on the judgment of the editors whether an article is up to snuff or not. That's why you can't count on them for solid, scientific scholarship.

Note:This is an entirely different concept from " Review Articles ."

How do I know if a journal publishes peer-reviewed articles?

Usually, you can tell just by looking. A scholarly journal is visibly different from other magazines, but occasionally it can be hard to tell, or you just want to be extra-certain. In that case, you turn to Ulrich's Periodical Directory Online . Just type the journal's title into the text box, hit "submit," and you'll get back a report that will tell you (among other things) whether the journal contains articles that are peer reviewed, or, as Ulrich's calls it, Refereed.

Remember, even journals that use peer review may have some content that does not undergo peer review. The ultimate determination must be made on an article-by-article basis.

For example, the journal  Science  publishes  a mix  of peer-reviewed and non-peer-reviewed content. Here are two articles from the same issue of  Science . 

This one is not peer-reviewed:  https://science-sciencemag-org.ezproxy.lib.utexas.edu/content/303/5655/154.1  This one is a peer-reviewed research article:  https://science-sciencemag-org.ezproxy.lib.utexas.edu/content/303/5655/226

That is consistent with the Ulrichsweb  description of  Science , which states, "Provides news of recent international developments and research in all fields of science. Publishes original research results, reviews and short features."

Test these periodicals in Ulrichs :

• Advances in Dental Research
• Clinical Anatomy
• Molecular Cancer Research
• Journal of Clinical Electrophysiology
• Last Updated: Aug 28, 2023 9:25 AM
• URL: https://guides.lib.utexas.edu/journalarticles101

Scholarly Journal Publishing Guide

• Getting started
• 1. EDITORIAL BOARD
• 2. COPYRIGHT

Description

Editorial review, peer review, providing feedback to authors.

• 4. PRODUCTION
• 5. INDEXING & DISSEMINATION
• 6. EQUITY, DIVERSITY, & INCLUSION
• Open Journal System (OJS) - Version 3
• Best Practices

Unless otherwise noted, content is this guide is licensed under a Creative Commons Attribution 4.0 International License. 

The process by which articles will be evaluated is an important part of establishing a journal. 

Journals may decided to have different processes for different sections of the journal. For example, a commentary column may be reviewed only by the editor while a research article may be subjected to an anonymous peer review process. 

This section of the guide outlines the different types of review and provides some sample forms to assist in developing the review process. 

Editorial review is an assessment of an article undertaken by a member of the editorial staff. 

For some sections of the journal, editorial review may be the only assessment taken of an article. This is more often the case for non-research articles such as book reviews, commentary, opinion etc.(although in some journals these sections are peer-reviewed as well).

Editorial review is also a part of the peer-review process. Typically editors will take a first pass at an article to determine if it's worthwhile to send out for peer review. They will typically evaluate if the article is:

• Within the journal's scope
• Of sufficient quality to send out to peer review

Peer Review Process

Image credit. © Jessica Lange. Licensed under Creative Commons CC BY 4.0 International

For a light read on the perspective of being an editor see:

Looser, D.( 2016, June 25).  How your journal editor works. Chronicle of Higher Education . Retrieved from:  http://chronicle.com/article/How-Your-Journal-Editor-Works/236911?cid=rc_right 

Peer review is the process by which experts in the subject area review and article and provide their feedback. 

Journals typically have between 1-3 reviewers per article depending on the journal's review criteria and the availability of reviewers. 

Journals should establish how they will recruit peer reviewers. For example, will a general call be put out on a listserv? Can anyone volunteer to be a peer reviewer or should there be an application procedure? If there's an application procedure, what's the criteria for acceptance?

Table 1: Different Types of Peer Review

* These terms were formerly referred to as single-blind and double-blind. Anonymous is now the preferred term. 

Source: pkp school,  different types of peer review, ensuring an anonymous review.

If the journal is using an anonymous review process, it should have instructions to editors and authors to properly anonymize a manuscript. This would include:

• e.g. "This study took place at McGill University..." rather, "This study took place at X University..."
• See pg. 3-4 of University of Chicago's document on anonymous reviews (PDF - 665 KB) for instructions for different versions of Word
• With PDFs, the Authors' names should also be removed from Document Properties found under File on Adobe Acrobat's main menu

Forms and guidelines for peer reviewers

Journals will typically provide guidelines for reviewers. This helps the reviews know how they should frame their assessment of the article. Some articles will also provide forms or rubrics for their peer reviewers to fill out. 

See below for several examples:

• European Journal of Immunology
• Journal of the American Board of Family Medicine

In either review scenario (e.g. editorial review or peer review), there is a set of typical language to provide feedback to authors about their article.

Journals can assist their peer reviews by providing their own definitions for recommendation decisions. 

Accept submission

• Submission is accepted for publication though it still may require copyediting. 

Accept pending revisions (Minor revisions)

• Submission is accepted for publication pending small revisions being made to the manuscript. 

Revisions required

• Greater revisions are required. Article is not accepted at this point. Requires further revisions and review before a publication decision can be made. Does not need to be resent to peer review, this process occurs between the editor and the author. 

Resubmit for review (Major revisions)

• Peer reviewers and/or editor determines the article requires extensive revisions and must undergo the peer review process again. 

Decline submission

• Article is not suitable for publication in this journal. 
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Literature Review vs Research Paper: What’s the Difference?

by  Antony W

June 26, 2024

This is a complete student’s guide to understanding literature review vs research paper.

We’ll teach you what they’re, explain why they’re important, state the difference between the two, and link you to our comprehensive guide on how to write them.

Literature Review Writing Help

Writing a literature review for a thesis, a research paper, or as a standalone assignment takes time. Much of your time will go into research, not to mention you have other assignments to complete. 

If you find writing in college or university overwhelming, get in touch with our literature review writers for hire at 25% discounts and enjoy the flexibility and convenience that comes with professional writing help. We’ll help you do everything, from research and outlining to custom writing and proofreading.

What is a Literature Review?

A literature review document is a secondary source of information that provides an overview of existing knowledge, which you can use to identify gaps or flaws in existing research. In literature review writing, students have to find and read existing publications such as journal articles, analyze the information, and then state their findings.

Credit: Pubrica

You’ll write a literature review to demonstrate your understanding on the topic, show gaps in existing research, and develop an effective methodology and a theoretical framework for your research project.

Your instructor may ask you to write a literature review as a standalone assignment. Even if that’s the case, the rules for writing a review paper don’t change.

In other words, you’ll still focus on evaluating the current research and find gaps around the topic.

Types of Literature Reviews

There are three types of review papers and they’re a follows:

 1. Meta-analysis

In meta-analysis review paper, you combine and compare answers from already published studies on a given subject.

2. Narrative Review

A narrative review paper looks into existing information or research already conducted on a given topic.

3. Systematic Review

You need to do three things if asked to write a systematic review paper.

First, read and understand the question asked. Second, look into research already conducted on the topic. Third, search for the answer to the question from the established research you just read.

What’s a Research Paper?

A research paper is an assignment in which you present your own argument, evaluation, or interpretation of an issue based on independent research.

In a research paper project, you’ll draw some conclusions from what experts have already done, find gaps in their studies, and then draw your own conclusions.

While a research paper is like an academic essay, it tends to be longer and more detailed.

Since they require extended research and attention to details, research papers can take a lot of time to write.

If well researched, your research paper can demonstrate your knowledge about a topic, your ability to engage with multiple sources, and your willingness to contribute original thoughts to an ongoing debate.

Types of Research Papers

 There are two types of research papers and they’re as follows:

 1. Analytical Research Papers

 Similar to analytical essay , and usually in the form of a question, an analytical research paper looks at an issue from a neutral point and gives a clear analysis of the issue.

Your goal is to make the reader understand both sides of the issue in question and leave it to them to decide what side of the analysis to accept.

Unlike an argumentative research paper, an analytical research paper doesn’t include counterarguments. And you can only draw your conclusion based on the information stretched out all through the analysis.

2. Argumentative Research Papers

In an argumentative research paper, you state the subject under study, look into both sides of an issue, pick a stance, and then use solid evidence and objective reasons to defend your position.

In   argumentative writing, your goal isn’t to persuade your audience to take an action. 

Rather, it’s to convince them that your position on the research question is more accurate than the opposing point of views.

Regardless of the type of research paper that you write, you’ll have to follow the standard outline for the assignment to be acceptable for review and marking.

Also, all research paper, regardless of the research question under investigation must include a literature review.

Literature Review vs Research Paper

The table below shows the differences between a literature review (review paper) and a research paper. 

Frequently Asked Questions

1. is there a literature review in a research paper.

A research paper assignment must include a literature review immediately after the introduction chapter.

The chapter is significant because your research work would otherwise be incomplete without knowledge of existing literature. 

2. How Many Literature Review Should Be in Research Paper?

Your research paper  should have only one literature review. Make sure you write the review based on the instructions from your teacher.

Before you start, check the required length, number of sources to summarize, and the format to use. Doing so will help you score top grades for the assignment. 

3. What is the Difference Between Research and Literature?

Whereas literature focuses on gathering, reading, and summarizing information on already established studies, original research involves coming up with new concepts, theories, and ideas that might fill existing gaps in the available literature.

4. How Long is a Literature Review?

How long a literature review should be will depend on several factors, including the level of education, the length of the assignment, the target audience, and the purpose of the review.

For example, a 150-page dissertation can have a literature review of 40 pages on average.

Make sure you talk to your instructor to determine the required length of the assignment.

5. How Does a Literature Review Look Like?

Your literature review shouldn’t be a focus on original research or new information. Rather, it should give a clear overview of the already existing work on the selected topic.

The information to review can come from various sources, including scholarly journal articles , government reports, credible websites, and academic-based books. 

About the author 

Antony W is a professional writer and coach at Help for Assessment. He spends countless hours every day researching and writing great content filled with expert advice on how to write engaging essays, research papers, and assignments.

• Open access
• Published: 30 August 2024

The effect of single versus multiple piezocisions on the rate of canine retraction: a randomized controlled trial

• Farah Y. Eid 1 &
• Ahmed R. El-Kalza 1  

BMC Oral Health volume  24 , Article number:  1024 ( 2024 ) Cite this article

Metrics details

Piezocision is a minimally invasive surgical method aiming to accelerate tooth movement. However, its effect was found to be transient, appertaining to the regional acceleratory phenomenon (RAP). Hence, the aim of the study was to evaluate the effect of single and multiple piezocisions on the rate of orthodontic tooth movement (OTM). Moreover, the impact of both protocols on canine tipping and orthodontically induced inflammatory root resorption (OIIRR) has been assessed.

Thirty indicated patients for the therapeutic extraction of maxillary first premolars were enlisted in this split-mouth study, and they were randomly split into two equal groups, each including 15 subjects. In the Single Application Group (SAG), one side of the maxillary arch arbitrarily received a single piezocision before the onset of canine retraction, whereas in the Multiple Application Group (MAG), piezocisions were randomly performed on one side, three times on a monthly basis, over the 12-week study period. The contralateral sides of both groups served as the controls. Canine retraction was carried out bilaterally using nickel-titanium closed-coil springs, delivering 150 g of force, and the rate of tooth movement, as well as canine tipping were evaluated on a monthly basis, over a 3-month period. Cone-bean computed tomography scans were also conducted pre- and post- canine retraction, and OIIRR was assessed using Malmgren Index.

The reported outcomes revealed a significant increase in the amount of canine retraction, canine tipping, as well as root resorption scores on the experimental sides in both groups SAG and MAG post-retraction ( p  < 0.001). However, upon comparing the experimental sides in both groups, non-significant differences have been observed between them regarding all the assessed outcomes ( p  > 0.05).

Conclusions

Single and multiple piezocisions effectively accelerate OTM in comparison to conventional orthodontic treatment, with relative outcomes reported by both intervention frequencies. Accordingly, single piezocision is recommended as an adjunct to OTM. Furthermore, significant tooth tipping as well as a significantly higher root resorption risk accompanies both single and multiple piezocision applications in conjunction with OTM.

Name of the Registry

Clinicaltrials.gov

Trial Registration Number

NCT05782088

Date of Registration

23/03/2023 “Retrospectively registered”.

https://clinicaltrials.gov/ct2/show/NCT05782088

Peer Review reports

The prolonged orthodontic treatment period is usually a matter of serious concern for the patients, and it also results in several dental and periodontal side effects [ 1 , 2 , 3 ]. Moreover, the prolonged treatment duration has an adverse effect on patient compliance, and his/her willingness to continue treatment. Consequently, several methods aiming to accelerate orthodontic tooth movement (OTM) and lessen the treatment duration have been proposed, including surgical [ 4 , 5 ] and non-surgical adjuncts [ 6 ].

The suggested acceleratory surgical interventions include corticotomy, which is considered a significantly invasive technique, since it involves the elevation of a relatively large flap, followed by cortical bone cuts, all of which might result in post-operative complications [ 4 , 7 , 8 ]. Several other less invasive surgical methods have been proposed for the acceleration of OTM, such as micro-osteoperforations [ 9 , 10 ], corticison [ 5 , 11 ], as well as piezocision [ 12 , 13 ].

Piezocision is known to involve minor piezoelectric cuts without flap elevation [ 14 , 15 ]. The acceleratory effect of piezocision and all the other surgical methods is mainly credited to the regional acceleratory phenomenon (RAP), which involves a transient demineralization, together with a surge in cellular activity in the alveolar bone, in response to the cortical bone injury [ 16 ]. The impact of RAP has been reported to be temporary, and entirely reversible. Moreover, the magnitude of RAP was found to be dependent on the corticotomy depth [ 17 ].

The impact of piezocision on the rate of OTM has been investigated in several trials, and despite its effectiveness in accelerating tooth movement, its effect was found to be transient [ 18 , 19 ], which might be related to the temporary nature of RAP as previously explained. Therefore, it has been suggested that performing multiple piezocisions throughout the treatment might be helpful in prolonging and/or re-inducing the biological effect of RAP, and accordingly, maintain the acceleratory effect for a longer time [ 20 , 21 ].

With orthodontically induced inflammatory root resorption (OIIRR) being a commonly encountered iatrogenic repercussion of orthodontic treatment, the impact of the proposed methods for acceleration of OTM has been assessed regarding this issue, based on the rationale of decreasing treatment time could concurrently decrease the incidence or the severity of OIIRR. Accordingly, piezocision and OIIRR with OTM have been tested in several studies with contradictory findings being reported [ 22 , 23 , 24 ].

In conclusion, by reviewing the literature, no clinical trial has been conducted to investigate the impact of multiple piezocisions on the rate of tooth movement, except for one study employing an initial corticotomy followed by a second flapless corticotomy using piezosurgery after two months, to facilitate the traction of an impacted canine [ 25 ]. Therefore, the aim of our study was to assess and compare the effect of single versus multiple piezocisions on the rate of OTM, judged by the rate of canine retraction. Moreover, maxillary canine tipping, and OIIRR with both single and multiple piezocision techniques were evaluated pre- and post- canine retraction.

The null hypothesis was that there are no significant differences in the rate of canine retraction, the amount of experienced canine tipping during movement, and in the risk of OIIRR with both single and multiple piezocisions.

Materials and methods

Study design.

The study was a compound design randomized controlled trial, comprising two parallel groups, with a split-mouth design in each.

Study subjects

Thirty participants with an age ranging from 15 to 25 years, have been appointed for this study. The sample size was calculated based on 95% confidence level to detect differences in the canine retraction rate with and without piezocision. Alfawal et al [ 15 ] reported that the mean ± SD canine retraction rate at the third month = 1.10 ± 0.29 mm/month on the piezocision side, and 0.98 ± 0.22 mm/month on the control side. The mean ± SD difference = 0.11 ± 0.255, and 95% confidence interval= -0.04, 0.26. Repeated piezocision is assumed to accelerate orthodontic tooth movements [ 20 ]. Based on comparison of paired means, the minimum sample size was calculated to be 14 per group, increased to 15 to make up for cases lost to follow-up. The total required sample size = number of groups × number per group = 2 × 15 = 30 patients [ 26 ]. The sample was calculated using MedCalc Statistical Software version 19.0.5 (MedCalc Software bvba, Ostend, Belgium; https://www.medcalc.org ; 2019).

Ethical approval has been procured from the Institutional Review Board of the Faculty of Dentistry, Alexandria University, Alexandria, Egypt (IRB:00010556–IORG:0008839). Manuscript Ethics Committee number 0582-01/2023. Patients were recruited from the outpatient clinic, Department of Orthodontics, Alexandria University starting January 2023, and the study was terminated in January 2024. Subjects were examined and screened, and the following enrolment criteria have been considered: (1) Class I bimaxillary protrusion, and Class II division 1 patients requiring the extraction of maxillary 1st premolars with consequent canine retraction, (2) Healthy systemic condition with no chronic problems, (3) No previous orthodontic treatment, (4) Acceptable oral hygiene, (5) Healthy periodontium. The study procedures were thoroughly explained to all the enrolled subjects, and signed informed consents were attained accordingly. All research procedures were performed in agreement with the relevant guidelines and regulations, as stated in the Declaration of Helsinki.

Patients requiring the therapeutic extraction of maxillary 1st premolars bilaterally (P), were tested for piezocision along with canine retraction (I), applied only once versus multiple times (C), to evaluate the difference in the rate of tooth movement with both protocols (O).

Randomization and subject allocation

The thirty recruited patients were randomly allocated to either group (15 per group), using a computer-generated randomization code (Sealed Envelope Ltd). As per the split-mouth design within each group, the randomization process was repeated once again for allocation of the “experimental” and “control” sides in the maxillary arch. Randomization was performed by a trial independent person.

Patients’ preparation

Preparation for fixed orthodontic treatment entailed recording the enrolled subjects’ medical and dental history, along with collecting the customary orthodontic records (photographs, x-rays, and study models). Oral hygiene reinforcement was also mandatory prior to the onset of orthodontic treatment. Maxillary and mandibular straight wire fixed Roth appliances (Sprint ® II; Forestadent, Germany) were bonded by the same operator, with 0.022 \(\:\:\times\:\:\) 0.028-inch slots in all participants, after which they were referred for maxillary first premolars’ extraction. Levelling and alignment were then started, and a wire sequence of 0.014-inch, 0.018-inch, followed by 0.016 \(\:\:\times\:\:\) 0.022-inch NiTi wires were used, over an approximate period of 3–4 months. This stage was considered achieved when a 0.016 \(\:\:\times\:\:\) 0.022-inch stainless steel arch wire was positioned passively in all the maxillary teeth, on which canine retraction will be performed.

Anchorage preparation

After levelling and alignment, anchorage reinforcement was ensured through the bilateral inter-radicular placement of mini-screws between the maxillary second premolars and first molars, 8 mm from the apex of the interdental papilla. The placed mini-screws were 1.7 mm in diameter, and 8 mm in length (Orthoeasy; Forestadent, Germany). Mini-screws were installed under local anesthesia, with a screw driver employed for the self-drilling process.

Intervention

In group SAG, piezocision was performed only once prior to the commencement of canine retraction (T0) on one side of the maxillary arch that has been randomly selected. As for the MAG group, piezocision was repeated three times, on a monthly basis (T0, T1, and T2), over the 12-week study period. The contralateral sides in both groups represented the controls.

On the experimental sides in both groups, the surgical procedure was conducted under local infiltrative anaesthesia to the mesial and distal sides of the maxillary canine. Vertical interproximal incisions were made 5 mm apical to the mesial and distal interdental papilla of the experimental canine, on the buccal aspect using surgical blade No. 15. Incisions extended apically 10 mm in length through the periosteum, permitting the blade to reach the alveolar bone. A Piezo surgical knife (Piezomed, tip B1) was subsequently employed to create the cortical bone incision through the gingival opening, to an approximate depth of 3 mm ( Fig.  1 ) . No suturing has been required for the soft tissue incisions after termination of the surgery [ 18 , 27 ]. Moreover, analgesics (paracetamol) were prescribed post-operatively, whereas anti-inflammatory drugs were prohibited to avoid intervening with the RAP [ 18 ].

(A) Vertical interproximal incisions mesial and distal to the maxillary canine using surgical blade No. 15. (B) Vertical cortical cuts using the Piezo surgical knife, with a depth of 3 mm

Canine retraction was accomplished using nickel-titanium (NiTi) closed-coil springs stretched between the canine bracket hook and the mini-screw head, with a force of 150 g applied on each side of the maxillary arch, and the force magnitude was adjusted each visit, as measured by a force gauge (Morelli Ortodontia, Brazil) (Fig.  2 ).

Canine retraction using NiTi closed-coil springs bilaterally stretched between the mini-screw head and the canine bracket hook

Due to the nature of the clinical procedure, neither the patient nor the operator could be blinded during the intervention. However, both the operators during measurements, and the statistician during data analysis were blinded.

Alginate impressions (Ca37; Cavex, Haarlem, The Netherlands) were taken before the start of canine distalization (T0), and then repeated on a monthly basis (T1, T2, T3) over the 12-week research duration. Dental models were then poured, coded, and scanned (inEos X5 CAD/CAM lab scanner; Dentsply Sirona, PA, USA), producing three-dimensional (3D) digital images of the fabricated models. The needed measurements were carried out using AutoCAD version 2020 (AutoCAD; Autodesk, USA). Pre-retraction and post-retraction cone-beam computed tomography (CBCT) scans were also conducted in both groups SAG and MAG (within a 12-week interval). A research design flowchart is represented in Fig.  3 , recapitulating the research methodology.

Research design flowchart summarizing the study procedures

Measurement of canine retraction

Various landmarks were determined on the maxillary arch, including the mid-palatal raphe, the medial points on the third right and left rugae, and the cusp tips of the right and left maxillary canines. From both the medial points of the right and left third rugae, and the cusp tips of the right and left maxillary canines, perpendicular lines were dropped to the mid-palatal raphe. Antero-posterior measurements were subsequently performed between the canine lines and the third rugae lines on each side, for the assessment of the canine retraction rate [ 28 ] (Fig.  4 ).

Measurement of canine retraction using AutoCAD between the canine cusp tips and the medial ends of the third rugae

Measurement of canine tipping

Tipping of the maxillary canine during retraction was evaluated by drawing vertical lines on the palatal surfaces of the lateral incisor and the canine that extend from the middle of the incisal edge of the lateral incisor and the cusp tip of the maxillary canine to the middle of the cervical line of each, thereby dividing each of them into equal halves. The distance between the lateral incisor and the canine was assessed at two points on their clinical crowns: incisal, and cervical, enabling the detection of crown tipping of the canine during distalization, if there was a difference in the measurements between both the assessed levels [ 9 ] (Fig.  5 ).

Evaluation of canine tipping using AutoCAD by measuring the distance between the canine and lateral incisor at the incisal and cervical levels

Measurement of OIIRR

In both groups, maxillary canine root resorption was evaluated on the procured pre-retraction and post-retraction CBCT scans, that were conducted using the J. Morita R100 Cone beam 3D Imaging System machine (MFG Corp., Kyoto, Japan). The scan was executed with a Field of View (FOV) of 100 × 50 mm (Width × Height). Volumes’ reconstruction was carried out with a 0.160 mm isometric voxel size, a tube voltage of 90 kVp and 8 mA, and an exposure time of 20 s.

Malmgren Index [ 29 ] was used for the assessment of OIIRR, and each of the tested canines was given a score ranging from 0 to 4, according to the degree of detected resorption. Using the software OnDemand3D ™ (Cybermed Inc., South Korea), and utilizing the arch section module, the focal trough was adjusted twice to allow the mesiodistal and the labiolingual sectioning of each canine, parallel to the long axis of its root (Fig.  6 ). The chosen slice thickness interval was 0.1 mm. The two perpendicular cross-sections showing the maximum length of the canine root were subsequently selected for evaluation using the designated index [ 30 ] (Fig.  7 ).

Axial views showing the adjusted focal trough permitting the sectioning of the right maxillary canine with an interval of 0.1 mm in two directions: (A) Labiolingual, (B) Mesiodistal

The re-oriented CBCT image of the maxillary canine revealing the maximum root length. (A) Labiolingual cross-section, (B) Mesiodistal cross-section

Intra-rater and inter-rater reliability

Calibration on the study measurements was performed for two assessors (F.E., and A.E.), who repeated the measurements to ensure consistency, within a one-week interval. Both intra- and inter-rater reliability were evaluated, and intraclass correlation coefficient (ICC) ranged from 0.87 to 0.99 indicating excellent reliability between examiners and across time [ 31 ].

Statistical analysis

Normality was tested for the included variables using descriptive statistics, plots (Q-Q plots and histograms), and Shapiro Wilk normality tests. All quantitative data exhibited normal distribution, so means and standard deviation (SD) were calculated, and parametric tests were implemented. Comparisons of canine retraction and tipping between the two groups (single vs. multiple piezocision) were performed using independent samples t-test, while comparisons between the experimental and control sides were performed using paired samples t-test. Mean differences and 95% confidence intervals were calculated. Meanwhile, comparisons between different time points were performed through repeated measures ANOVA, followed by multiple pairwise comparisons with Bonferroni adjusted significance levels. Comparisons of root resorption scores between the two groups (single vs. multiple piezocision) were done using Mann-Whitney U test, whereas comparisons between the experimental and control sides, and between the pre- and post- scores were performed using Wilcoxon Signed Ranks test. The significance level was set at p-value < 0.05. Data analysis was performed using IBM SPSS for Windows (Version 26.0).

Over the study period, no subject dropouts were recorded neither in the pre-intervention period, nor throughout the remainder of the research duration. Non-significant differences have been reported between the enrolled participants in the two study groups regarding their baseline characteristics ( p  > 0.05), as displayed in Table  1 . No mini-screw failures have also been reported in any of the study participants over the 12-week observation period. Moreover, all the study models that were obtained every month, as well as the pre- and post-retraction CBCT scans were accounted for.

• Canine retraction

The amount of maxillary canine distalization at the studied time points is depicted in Table  2 , regarding both groups SAG and MAG. In group SAG, the mean distance travelled by the canines has been significantly greater on the experimental sides in comparison with the control sides at all the assessed time points ( p  < 0.001), in addition to the total moved distance after the 12-week study period, with that being 4.49 mm ± 0.34 on the experimental side, and 2.77 mm ± 0.29 on the control side. Moreover, on the experimental side, the amount of the canine retraction was significantly less at T3 when compared to those recorded at T1 and T2 ( p  < 0.01). Opposingly, on the control side, non-significant differences have been observed in the amount of retraction across time ( p  = 0.09).

In group MAG, a similar pattern to that observed in the SAG has been documented, with the experimental sides showing statistically greater moved distances by the maxillary canines at T1, T2, and T3 in comparison with the control sides ( p  < 0.001). Also, the total amount of canine retraction achieved on the experimental side was statistically higher than that recorded on the control side, with values of 4.68 mm ± 0.27, and 2.79 mm ± 0.29, respectively. The experimental side showed a significant reduction in the moved distances by the canines at T3 in comparison with both T1 and T2 ( p  < 0.001), whereas the control side revealed a relatively constant rate of tooth movement across the three time points ( p  = 0.12).

When the experimental sides in both groups SAG and MAG were compared as presented in Fig.  8 , non-significant differences between both groups have been documented at T1 ( p  = 0.11), T2 ( p  = 0.10), T3 ( p  = 0.68), as well as in the total moved distance after 12 weeks ( p  = 0.11). However, a significantly less amount of canine retraction was recorded at T3 in comparison to T1, and T2 ( p  < 0.001).

Comparison of canine retraction on the experimental sides in groups SAG and MAG

Canine tipping

Canine tipping on both the experimental and control sides in groups SAG and MAG is displayed in Table  3 . In the two study groups, a similar trend has been observed on both the experimental and control sides, where a significant increase in the moved distance by the maxillary canine has been documented relative to the lateral incisor at the incisal, and cervical levels, as well as after calculating the difference between both levels at all the assessed time points ( p  < 0.001). Furthermore, in both single and multiple application groups, a statistically greater amount of maxillary canine tipping has been noted on the experimental sides relative to the control sides at all the measured levels (incisal, cervical, difference between both), and at all the evaluated time points aside from the baseline (T0) ( p  < 0.05).

In Table  4 , comparisons between the amount of resultant canine tipping post-retraction on the experimental sides in groups SAG and MAG are displayed. Statistically non-significant differences have been reported between both groups at all the assessed levels and time points ( p  > 0.05). Within group comparisons showed statistically significant differences in the amount of canine tipping at all the time points, and at all the evaluated levels ( p  < 0.001).

Malmgren Index scores for OIIRR of the maxillary canines in both groups SAG and MAG, on the experimental and control sides are represented in Table  5 . Within each of the tested sides, a significant score change has been documented denoting an increased incidence and/or severity of OIIRR post-retraction on the experimental sides in the SAG and MAG groups ( p  < 0.001), and on the control sides in SAG ( p  = 0.08) and in MAG ( P  = 0.03).

Upon comparing the root resorption changes between the experimental sides in the two groups as displayed in Fig.  9 , non-significant differences have been observed between them following canine distalization ( p  = 0.81).

Comparison of root resorption scores on the experimental sides in groups SAG and MAG

With surgical methods being reported as effective acceleratory adjuncts to OTM, minimally invasive options are always advocated by both clinicians and patients. Hence, the objective of this study was to evaluate and compare the influence of single versus multiple piezocisions on the canine retraction rate. Moreover, canine tipping and root resorption were evaluated with both piezocision protocols. According to the reported results, the null hypothesis has been accepted as non-significant differences have been documented between single and multiple piezocision applications in all the measured outcomes, whether the amount of tooth movement, tipping, or the associated OIIRR.

The employed study design in the present investigation was a compound design randomized controlled trial (RCT), pertaining to RCTs being beheld as the benchmark for evaluation of intervention efficiency [ 32 ]. Furthermore, the split-mouth technique limited the influence of inter-subject variability, with the enrolled participants acting as their own controls, thereby decreasing the required sample size [ 33 ].

Extractions were scheduled at the beginning of orthodontic treatment, just after fixed appliance bonding, thus considerable time has been allowed between the extraction date and the onset of canine retraction. This sequence has been planned because extraction is considered a traumatic surgical procedure, that can induce RAP and alter the tooth movement rate, thereby obscuring the effect of the tested surgical intervention [ 34 ]. A similar precaution has been taken by several investigators [ 9 , 35 ].

NiTi closed-coil springs were used to retract the maxillary canines in both groups, for the purpose of generating continuous forces throughout the 12-week assessment period [ 36 ]. Moreover, the medial ends of the third rugae were used a stable reference points for the measurement of canine retraction [ 37 ], as performed in former studies [ 6 , 15 ].

The CBCT scans performed by the enlisted participants pre- and post-retraction (12-week interval) were imperative for assessing the influence of piezocision on root resorption. It is noteworthy to mention that high intra-observer and inter-observer reliability have been advocated regarding CBCT measurements in several investigations [ 38 , 39 ]. Moreover, higher diagnostic accuracy has been reported with CBCTs when compared to periapical and panoramic radiographs with regards to the identification and diagnosis of root resorption [ 40 , 41 ]. On another note, Malmgren index [ 29 ] has been used in the present study as a reliable scoring system for root resorption evaluation, as well in other studies [ 30 , 42 ].

Results of the present study reported a significant increase in the amount of tooth movement on the piezocision sides in both the single and multiple application groups in comparison to the control sides, at all the assessed time points by approximately 62.5%. This resultant acceleration is mainly attributed to the RAP that has been induced by the surgical injury to cortical bone, and the consequent reduction in the bone resistance to tooth movement [ 16 , 43 ]. Furthermore, in response to the employed selective decortication, an increase in the inflammatory markers together with an elevation in the cytokines’ levels take place, prompting the activity of osteoclasts and enhancing the bone remodeling process, finally resulting in acceleration of OTM [ 44 , 45 ]. Findings reported in the present study are in agreement with those by Aksakalli et al [ 14 ], as well as Abbas et al [ 46 ], where piezocision was reported to significantly accelerate canine distalization into the extraction space by 1.5-2 times during the first three months of fixed appliance therapy.

Moreover, it has been observed that the greatest distances moved by the maxillary canines on the experimental sides in both groups were recorded in the 1st two months of treatment, followed by a significant decrease by the 3rd month, in contrast to the relatively constant rate of tooth movement on the control sides. However, despite the drop reported at T3, the distance travelled on the piezocision side was still significantly higher than that on the control side. A possible explanation has been provided by Wilcko et al [ 47 , 48 ], where they stated that RAP is a unique phenomenon that exhibits a distinct pattern in its emergence and extent, with its onset taking place only a few days post-injury, reaching its peak after 4 to 8 weeks, and lasting for 2 to 4 months. A relatively similar pattern of tooth movement has been reported by Alfawal et al [ 15 ] with both piezocision and laser-assisted flapless corticotomies during canine distalization, and again by Jaber et al [ 49 ] with laser-assisted flapless corticotomy.

The relatively similar distances moved by the maxillary canines on the experimental sides in both groups with single and multiple applications do not support the theory recommending repeating the surgical injury in an attempt to re-induce the RAP, and consequently maintain the acceleratory impact on the teeth during orthodontic treatment. This theory has been tested by Sanjideh et al [ 50 ], where a second corticotomy procedure was performed after 4 weeks after treatment onset, and was found effective in accelerating OTM over a longer duration. With piezocisions, the same hypothesis has been investigated by Charavet et al [ 20 ], where one-stage versus two-stage piezocisions were compared, and repeated injuries were found to effectively re-activate RAP. However, when the same hypothesis was tested clinically in the present study, non-significant differences have been found between single and multiple piezocisions, thereby refuting the theory due to its clinical and statistical non-significance. This level of insignificance between both techniques could be explained by Wilcko et al [ 47 , 48 ] as stated earlier, where they reported that RAP could last for up to 4 months, thus re-induction within 4 weeks is not needed.

Significant tipping of the maxillary canines in both groups has been reported on the experimental as well as on the control sides. This finding may be related to the direction of the force vector in the present study, which was in a distal and a relatively apical direction, since the NiTi coil springs were attached from the mini-screw head (8 mm apical to the apex of the interdental papilla, between the maxillary 2nd premolar and 1st molar), to the hook on the distal wing of the maxillary canine bracket. These findings are in accordance with those reported by Abbas et al [ 46 ] where significant tipping of the maxillary canines was noted after retraction, with both piezocision and corticotomy procedures, in comparison with the controls. However, the non-significant differences between both experimental sides (single and multiple piezocision) in the resultant tipping movement could be related to the non-significant differences between them in the rate of tooth movement that has been reported earlier as well.

Analysis of the root resorption scores in the present study revealed a statistically significant difference between the experimental and control sides in both groups SAG and MAG, with more resorption related to both the single and the multiple surgical interventions. Comparative findings were reported by Elkalza et al [ 24 ] and Patterson et al [ 27 ], where significant root resorption has been recorded with piezocision-assisted orthodontics. Conversely, others reported significantly less root resorption with piezocision in comparison to conventional orthodontic treatment [ 46 ].

Even though the induced RAP following surgical injury is known to increase alveolar bone turnover through stimulating the accompanying cellular activity could possibly reduce the incidence of root resorption due to the remarkable reduction in the pressure areas [ 51 , 52 ], the precise association between alveolar bone density and OIIRR is quite perplexing. Contradictory findings have been reported in the literature regarding this issue, where some have suggested that the osteoporotic environment induced by corticotomy-related procedures favor bone remodeling around the roots [ 53 ], whereas others documented an increase in OIIRR with the increased bone turnover rate [ 54 ]. On a cellular level, three weeks post-corticotomy, an increase in osteoclast number has been noted in conjunction with a surge in the bone turnover rate, which was attributed to the RAP response [ 55 ]. On a biological level, Teng and Liou [ 56 ] found that bone remodeling markers from the gingival crevicular fluid, such as bone-specific alkaline phosphatase showed a constant increase throughout the experimental period following interdental cuts between the teeth in Beagle dogs. Furthermore, the experimental dogs did not encounter a systemic increase in bone turnover, as depicted through serum alkaline phosphatase levels, thus it has been concluded that the RAP response is experienced locally, and that the extent of the osteotomy is possibly directly related to the intensity of bone turnover and the associated osteoporotic changes. Accordingly, it could be argued that the increased clastic cellular activity during the enhanced turnover process, could possibly increase the expected amount of OIIRR.

Moreover, RAP has been reportedly associated with an increase in the local inflammatory response [ 51 ], with a consequent significant increase in inflammatory markers such as cytokines and chemokines at the injury site [ 9 ]. Since OIIRR is considered an inflammatory process, the elevated levels of inflammatory mediators induced by RAP and surgical injuries could be possible risk factors for root resorption [ 57 ].

Study limitations

Limitations of the present study include the lack of assessment over a longer period and repeating the intervention after 2 or 3 months instead of every month, covering the entire orthodontic treatment duration. Therefore, future studies are recommended to extend past the canine retraction stage for a more comprehensive appraisal. Additionally, a larger sample size would have aided in the generalizability of the obtained results. It is also noteworthy to mention that the lack of operator blinding during the intervention could result in potential bias. Nonetheless, specific measures were taken to manage this downside, including the randomized subject allocation, as well as blinding of the operators during both the measurement and the data analysis phases.

Assessment of patient reported outcome measures are also advocated, such as pain, discomfort, functional limitation, periodontal side effects, in addition to patient acceptability to the repeated interventions. Moreover, measurement of maxillary canine tipping has been performed relative to the lateral incisor, hence, its assessment relative to a more stable reference point is recommended for a more accurate evaluation.

Considering the present study’s 12-week interval, single and multiple piezocisions effectively accelerate OTM in comparison to conventional orthodontic treatment, with relative outcomes reported by both intervention frequencies. Accordingly, single piezocision is recommended as an adjunct to OTM.

Given the employed mechanics for canine retraction in the present study, significant tooth tipping accompanies accelerated OTM with both single and multiple surgical interventions, with comparable amounts using both protocols. Therefore, bodily tooth movement is less encountered in conjunction with piezocision-assisted orthodontics.

Incidence of OIIRR is significantly higher with both single and multiple piezocison applications in contrast to OTM solely, which could be related to the enhanced clastic cellular activity at the injury sites. Approximate OIIRR risks have been documented using both protocols.

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

Orthodontic tooth movement

Regional acceleratory phenomenon

Orthodontically induced inflammatory root resorption

Nickel-titanium

Three-dimensional

Cone-beam computed tomography

Field of view

Intraclass correlation coefficient

Standard deviation

Randomized controlled trial

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F.E.: Conceptualization, data curation, analysis and interpretation of the study results, writing and preparing the original manuscript, reviewing and editing. A.E.: Supervision, conceptualization, performing the clinical procedures, revising the written manuscript, and helping in drawing out the final study conclusions. All authors reviewed the manuscript.

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Eid, F.Y., El-Kalza, A.R. The effect of single versus multiple piezocisions on the rate of canine retraction: a randomized controlled trial. BMC Oral Health 24 , 1024 (2024). https://doi.org/10.1186/s12903-024-04716-6

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Mouse embryo CoCoPUTs: novel murine transcriptomic-weighted usage website featuring multiple strains, tissues, and stages

• Sarah E. Fumagalli 1   na1 ,
• Sean Smith 2   na1 ,
• Tigran Ghazanchyan 2   na1 ,
• Douglas Meyer 1 ,
• Rahul Paul 2 ,
• Collin Campbell 2 ,
• Luis Santana-Quintero 2 ,
• Anton Golikov 2 ,
• Juan Ibla 3 ,
• Haim Bar 4 ,
• Anton A. Komar 5 ,
• Ryan C. Hunt 1 ,
• Brian Lin 1 ,
• Michael DiCuccio 6 &
• Chava Kimchi-Sarfaty 1  

BMC Bioinformatics volume  25 , Article number:  294 ( 2024 ) Cite this article

Metrics details

Mouse ( Mus musculus ) models have been heavily utilized in developmental biology research to understand mammalian embryonic development, as mice share many genetic, physiological, and developmental characteristics with humans. New explorations into the integration of temporal (stage-specific) and transcriptional (tissue-specific) data have expanded our knowledge of mouse embryo tissue-specific gene functions. To better understand the substantial impact of synonymous mutational variations in the cell-state-specific transcriptome on a tissue’s codon and codon pair usage landscape, we have established a novel resource—Mouse Embryo Codon and Codon Pair Usage Tables (Mouse Embryo CoCoPUTs). This webpage not only offers codon and codon pair usage, but also GC, dinucleotide, and junction dinucleotide usage, encompassing four strains, 15 murine embryonic tissue groups, 18 Theiler stages, and 26 embryonic days. Here, we leverage Mouse Embryo CoCoPUTs and employ the use of heatmaps to depict usage changes over time and a comparison to human usage for each strain and embryonic time point, highlighting unique differences and similarities. The usage similarities found between mouse and human central nervous system data highlight the translation for projects leveraging mouse models. Data for this analysis can be directly retrieved from Mouse Embryo CoCoPUTs. This cutting-edge resource plays a crucial role in deciphering the complex interplay between usage patterns and embryonic development, offering valuable insights into variation across diverse tissues, strains, and stages. Its applications extend across multiple domains, with notable advantages for biotherapeutic development, where optimizing codon usage can enhance protein expression; one can compare strains, tissues, and mouse embryonic stages in one query. Additionally, Mouse Embryo CoCoPUTs holds great potential in the field of tissue-specific genetic engineering, providing insights for tailoring gene expression to specific tissues for targeted interventions. Furthermore, this resource may enhance our understanding of the nuanced connections between usage biases and tissue-specific gene function, contributing to the development of more accurate predictive models for genetic disorders.

Peer Review reports

Mouse embryology and tissue-specific transcriptomics stand at the forefront of developmental biology, providing invaluable insights into the intricate processes that govern embryonic development and tissue differentiation [ 1 , 2 , 3 ]. Mus musculus has become an essential organism for studying embryogenesis due to its genetic proximity to humans, short reproductive cycles, and well-characterized genome. Investigating the dynamic changes in gene expression during different stages of mouse embryonic development offers a comprehensive view of the molecular events driving tissue specification [ 4 , 5 , 6 , 7 , 8 ].

Tissue-specific transcriptomics has given researchers a unique opportunity to dive deeper into gene expression profiles, unraveling the spatiotemporal intricacies of embryonic development. Recently, tissue-specific transcriptomics has revealed many normal and disease-specific gene expression associations. Joining transcriptomics and epigenetics helped identify several neuronal repressors enriched during early development [ 9 ]. Zhao et al. (2022) collected mouse embryo gut tissue samples spanning E9.5 to E15.5 to create a spatiotemporal transcriptome map, revealing critical developmental decisions are regulated by mesenchymal-epithelial interactions [ 10 ]. The integration of mouse embryology with tissue-specific transcriptomics not only advances our understanding of normal development but also unveils potential links to congenital disorders, paving the way for innovative therapeutic strategies and precision medicine approaches [ 11 , 12 ]. Although the biological processes of developmental embryonic stages are well-established, the exact factors dictating genetic programming during development and the impact of variations in the cell-state-specific transcriptome on healthy tissue development in prenatal stages remain elusive.

To help close this gap and aid further embryology research, we combined temporal murine tissue-specific transcriptomics and gene-specific usage data from a collection of bulk RNA-seq mouse embryo samples sourced from three archives, more than 80 published articles, and more than 20,000 associated RefSeq Select gene transcripts [ 13 ]. Following different types of usage bias, such as GC, dinucleotide, junction dinucleotide, codon, and codon pair, over time have shown useful in distinguishing between species, variants, and strains [ 14 , 15 , 16 , 17 , 18 ], as a rationale for transcript design [ 19 ], for optimization and deoptimization projects, and many others [ 20 , 21 , 22 , 23 ].

GC content in the third position of a codon (GC3%) has been shown to be an important influence on gene expression patterns associated with distinct stages of development [ 24 , 25 ]. Moreover, the utilization of codons ending with CG dinucleotides, especially in genes containing CG islands, are essential for proper development [ 26 ]. Fornasiero and Rizzoli [ 27 ] found predominantly A- or U-ending codons in cancerous tissue over control across 75 datasets and 40 pathologies, with a direct causal link to transcript production [ 27 ].

Here, we generated a new publicly accessible resource, Mouse Embryo CoCoPUTs website [ 13 ], to provide the median transcriptomic-weighted usage values for 1,381 mouse embryo samples. Mouse Embryo CoCoPUTs provides users access to GC, dinucleotide, junction dinucleotide, codon, and codon pair usage types that are easily downloadable and automatically displayed as tables, bar graphs, and heatmaps for each strain and embryonic stage of choice [ 13 ]. This webpage provides tissue- and stage-specific usage data for strain C57BL/6 (the most widely used inbred strain), the Jackson Laboratory strains C57BL/6N and C57BL/6J, and an outbred strain CD-1, which can be easily compared to usage values of a variety of organisms [ 28 ], human tissues [ 28 ], and cancers [ 29 ]. This tool can be used to characterize differences in usage patterns between disease and non-disease genes [ 30 , 31 , 32 , 33 ] and genes that have been identified as potential druggable targets [ 34 , 35 ]. Similar webpages like CoCoPUTs [ 36 ], TissueCoCoPUTs [ 28 ], and CancerCoCoPUTs [ 29 ] have proven to be useful resources in identifying usage differences among organisms, human tissue types, and cancer types, respectively.

Construction and content

Data collection and sample selection.

Data was collected from NCBI Sequence Read Archive [ 37 ], Mouse Genome Informatics RNA-Seq and Microarray Experiment Search database [ 38 ], and literature search was utilized to identify bulk RNA-seq mouse embryo samples from one of four strains: C57BL/6, C57BL/6J, C57BL/6N, and CD-1 (Additional File 1 and 2 ). Sex included male, female, and pooled. Cross-strain or genetically modified samples were removed, as well as samples receiving drug treatments or specialized diets. Samples from cultured cells were not included. Fastq files for 1,381 samples across 84 publications and projects were downloaded from NCBI [ 37 ]. Downloaded data comprised of single- and paired-end reads sequenced on AB SOLiD, Helicos Heliscope, or Illumina sequencers. We calculated transcript per million values using DRAGEN v3.7.5 [ 39 ] with the following parameters:

--enable-duplicate-marking true --enable-rna true --enable-rna-quantification true --annotation-file GCF_000001635.27_GRCm39_genomic.gtf.

Reads were aligned to the GRCm39 mouse reference genome and annotation file based on strain C57BL/6J (mm39, GCF_000001635.27) obtained from NCBI [ 37 ]. To automate DRAGEN analysis, processing was performed on the High-performance Integrated Virtual Environment [ 40 ]. We removed 22 pseudogenes from the 21,210 RefSeq and transcripts per million data that were identified via the C57BL/6NJ pseudogenes from the website Mouse Strains Pseudogenes (ADAM1A, ADAM1B, ADAM5, ATP6AP1L, FADS2B, FER1L4, GGNBP1, GLRA4, GLYCAM1, GUCY1B2, LY6G6E, MFSD13B, MPTX1, NPY6R, OFCC1, SERHL, SMPD5, TDH, TMCO5B, TMEM198B, TRPC2, and UOX) [ 41 ]. This resulted in 20,903 genes for further analysis.

Transcriptome-weighted usage calculations

Gene-specific dinucleotide, junction dinucleotide, codon, and codon pair counts were prepared as matrices. Each value represents the number of times a particular codon (for example) appears in the coding sequence of a specific gene’s primary transcript. A median sample was constructed by computing the median transcript per million across all samples for a particular embryonic tissue type and stage. Using dot multiplication to multiply the sample gene counts (transcripts per million table) and the gene usage values results in the transcriptome-weighted dinucleotide, junction dinucleotide, codon, or codon pair usage values. This calculation was applied to four embryonic strains (C57BL/6, C57BL/6J, C57BL/6N, and CD-1), 15 tissue types, 18 Theiler stages (TS), and 26 embryonic days (Table  1 ). Dinucleotide, junction dinucleotide, and codon values were then normalized to one thousand and codon pair usage to one million. The metadata of the embryonic samples can be found in Additional File 2 . The 15 tissue categories discussed here and found on the Mouse Embryo CoCoPUTs are a generalization of many highly specific tissues listed in Additional File 3 under the “Mouse Embryo” tab.

Mouse Embryo CoCoPUTs

In our research, we developed a dashboard using Shiny (version 1.7.5) within the R programming environment (version 4.1.3), aiming to provide visual insights and facilitate interactive data exploration in a manner akin to the CoCoPUTs [ 36 ] methodology, all built upon the HIVE [ 40 ]. HIVE, noted for its efficiency in handling, analyzing, and storing vast datasets, serves as the backbone for our application's data management capabilities.

Shiny [0.2] has become a cornerstone in the R community for crafting dynamic web applications and dashboards. It uniquely integrates data analysis, visualization, and user interaction directly within the R ecosystem. Our dashboard's design incorporates a variety of user interface elements, including dropdown menus, tabs, buttons, and interactive plots, to foster an engaging user experience. On the server side, we employ functions to perform computations, generate visualizations, and dynamically update the user interface (UI) in response to user inputs. These server-side functions are crucial for seamlessly handling the intricate backend processes underlying the dashboard’s operational logic.

The adoption of Shiny's reactive programming model is instrumental in our dashboard, enabling a fluid dialogue between the UI and server-side components. This model ensures that the dashboard can respond to user interactions with real-time updates. Moreover, we have enhanced the dashboard's visual aesthetics and functionality by incorporating custom CSS and HTML, alongside integrating external libraries such as Plotly. This integration not only elevates the dashboard’s design but also enriches its interactivity, offering users sophisticated, interactive plots that enrich their data exploration experience.

Example data analysis

The example data analysis discussed in this paper resulted from downloading the central nervous system samples across all TS from Mouse Embryo CoCoPUTs [ 13 ]. Heatmaps were developed to highlight the differences and similarities in GC, dinucleotide, junction dinucleotide, codon, and codon pair usage over each TS. We also compared the embryonic usage data to human usage data following the ratio of mouse embryo by human usage. We downloaded human tissue-specific data from TissueCoCoPUTs [ 13 ] and sorted the tissues into the more general categories used for the embryonic tissues (Additional File 3 ). Heatmaps were used to demonstrate biases and changes to usage and were created using Python (version 3.10.4) library Seaborn [ 42 ] and the graphics environment Matplotlib [ 43 ].

Significance was calculated between strains at each time point for a particular usage type (Additional File 4 ). For example, we tested whether C57BL/6 AAG (Arg) codon distribution was significantly different than C57BL/6J AAG codon distribution during the embryonic stage TS20. These comparisons were calculated per strain per TS for each usage type. We also compared TS within each strain for each usage type. We used Python’s (version 3.8) SciPy library [ 44 ], and Pandas to run a two-sided Mann–Whitney U test to find the raw p -values for each of the tests performed. Applying the statsmodels multipletests package (version 0.15.0), we adjusted the p -values using the Bonferroni correction (0.05/N), where significance is dependent on the number of tests performed (N). If the raw p -value is less than the adjusted threshold, the null hypothesis is rejected. The magnitude of the p -value, effect size, is determined by calculating Cohen’s D, with the expectation of unequal variances (Additional File 4 ). Effect sizes can be ‘very small’ (0—0.1), ‘small’ (0.2—0.35), ‘medium’ (0.36—0.65), ‘large’ (0.66—0.9), and ‘very large’ (> 1).

Utility and discussion

User walkthrough of mouse embryo cocoputs.

Mouse Embryo CoCoPUTs is the first website to provide easily accessible transcriptomic-weighted murine embryo GC, dinucleotide, junction dinucleotide, codon, and codon pair usage data for a variety of embryonic strains, tissues, and stages [ 13 ]. Mouse Embryo CoCoPUTs makes it easy to compare embryonic usage data by either downloading the data for local use or by leveraging the tables, bar graphs, and heatmaps that are automatically generated upon search inquiries (Fig.  1 ).

Mouse Embryo CoCoPUTs webpage interface. Users can search data tables by selecting one of four strains, one or more tissues, and one or more stages. Multiple queries produce a comparison under each Results tab. Files can be downloaded individually or as a package within the Results tabs and under the ‘Additional Files to Download’ tab

Once a user has input strain(s), tissue(s), and stage(s) into the Mouse Embryo CoCoPUTs query, results will quickly populate under the tabs on the left-hand side as seen in Fig.  1 , also shown in Panel A of Fig.  2 [ 13 ]. Tabs ‘Codon Usage Bar Chart’ and ‘Dinucleotide Frequency Bar Charts’ provide the user with bar charts representing transcriptome-weighted codon usage (Panel B), dinucleotide usage, junction dinucleotide usage, and GC content. Tabs ‘Codon Usage Table’, ‘Dinucleotide Table’, and ‘Codon Pair Usage Table’ show the median usage for each query in easily downloadable tables that look like table displayed in Panel C of Fig.  2 . Codon pair results were generated and can be found under the tab ‘Codon Pair Heatmap’ (Panel D). For graph clarity, it can be downloaded as a PNG or PDF. Query, result file descriptions, and a walk-through example can be found in the Help file (Fig.  2 Panel A at bottom).

Mouse Embryo CoCoPUTs User Search Results. After selecting one or more strains, tissues, and stages, results are populated under tabs located on the left side of the search screen seen in Panel A. Codon Usage Bar Chart (Panel B) and Codon Usage Table display the codon usage and GC content as bar graphs and tables. Dinucleotide Frequencies Bar Charts and Dinucleotide Table (Panel C) display dinucleotide and junction dinucleotide usage as bar graphs and tables. Codon Pair Heatmap (Panel D) and Codon Pair Usage Table provide the codon pair usage as a downloadable heatmap or table

To demonstrate the utility of the Mouse Embryo CoCoPUTs, we present an example of tissue-specific relationships across Theiler stages (TS) using the central nervous system (CNS) as a model tissue. First, we use heatmaps to provide a visualization of usage differences and similarities over time per mouse strain, and next, we compare mouse embryo to human CNS usage over time.

G/C heavy usage highlights embryonic mouse strain specific differences across Theiler stages

We were interested in investigating how different usages changed over time for stains C57BL/6, C57BL/6J, and CD-1 within our CNS Mouse Embryo CoCoPUTs temporal dataset. Figure  3 lists each strain and its stages on the y-axis and the type of usage along the x-axis (GC content, dinucleotide, junction dinucleotide, codon, and codon pair usage are respectively associated with Panels A, B, C, D, and E).

Mouse Embryo Usage over Theiler stage heatmaps for central nervous system genes. Each heatmap is subdivided on the y-axis by strain and Theiler stage. The darker the blue, the higher the usage. Panel A shows all strains have the least GC content in the second codon position. There is a strong preference for dinucleotide AG (Panel B) and junction dinucleotide CA (Panel C) for all strains. Codon usages are similar across all strains, leading with GAG (Gln) and AAG (Arg) (Panel D). Panel E describes the codon pair usage (scaled) for all synonymous Alanine:Alanine (AlaAla) and Alanine:Arginine (AlaArg) codon pairs, revealing very little variation in usage across strains than any other type of usage

Key findings

For all strains, GC usage is greatest in the third codon position (GC3%) and least in the second codon position (GC2%).

None of the strains used the TG dinucleotide or junction dinucleotide (removed from Fig.  3 Panels B and C).

All strains prefer consecutive nucleotides C and A between codons as junction dinucleotides, suggesting within codon positioning may play an important role in development.

Codons GAG (Glu), CAG (Gln), CTG (Leu), AAG (Lys), and GTG (Val) are frequently used across all strains and TS.

Codon pair usage was least variable between strains and stages, suggesting that the surrounding codon environment may be one variable that is most consistent between strains. Codon pair GCACGA (AlaArg) highlights the most divergence in usage for C57BL/6J compared to C57BL/6 and CD-1. Conversely, codon pair GCAGCT (AlaAla) is the most stable across strains.

The mouse embryo usage heatmaps overall highlight similarities in different types of usages between strains across stages of development. The lack of unique differences between these usage biases across murine strains suggest that similar gene expression patterns underlie the development of the CNS. Future studies may leverage this website to understand variation in other tissue types. To further distinguish whether unique CNS usage differences occur among strains through specific TS transitions, we generated heatmaps based on change in usage over time. By plotting the change over time, we can see more easily slight shifts in usage values.

Figure  4 consists of five panels depicting usage change over time for each strain as one moves down the y-axis (GC content, dinucleotide, junction dinucleotide, codon, and codon pair usage are respectively associated with Panels A, B, C, D, and E). Green represents an increased change in usage (for example, from TS19 to TS20), red represents a decreased change in usage, and yellow is centered on zero to represent no change from stage to stage.

Difference over Theiler stage heatmaps for central nervous system genes reveal repeated direction reversals. Each heatmap is subdivided on the y-axis by strain and Theiler stage. Each row represents the change in usage from one stage to the next. Green represents an increase in usage, red is a decrease in usage, and yellow is centered on no change. Panel A shows the most drastic fluctuations in GC3 percent for C57BL/6J in comparison to C57BL/6 and CD-1 changes. Central nervous system dinucleotides (Panel B) tend to fluctuate less in general than junction dinucleotides (Panel C). Codon usage differences shown in Panel D reveal the majority of changes with the greatest magnitude are found within the Theiler stages of C57BL/6J. Panel E describes the codon pair usage difference (scaled) for all synonymous Alanine:Alanine (AlaAla) and Alanine:Arginine (AlaArg) codon pairs. This heatmap shows many small changes in codon pair usage for each of the strains over time

Across all usage types, C57BL/6J CNS usage fluctuates more often than C57BL/6 and CD-1.

C57BL/6 completely reverses usage direction for CC and AA dinucleotides and junction dinucleotides.

Dinucleotide AC and junction dinucleotide GT were most consistent over time for all strains.

A and T leading junction dinucleotides tend to increase as C and G leading tend to decrease (most obvious trend in C57BL/6J.

Codon GAG (Glu) fluctuates more often than most other codons across all strains. At the end of TS22, C57BL/6 shows decline, while C57BL/6J shows an increase.

Synonymous codons from amino acids glutamine, glutamic acid, glycine, and proline (G and C leading) show the most dramatic changes over time.

C57BL/6 codon pair usage changes the most in the first and last TS, C57BL/6J is more uniform in its fluctuations over time, and CD-1 decreases activity as time progresses.

To identify usage comparisons that are statistically significant and their magnitudes for both within and between strains, we used the two-sided Mann–Whitney U test (Bonferroni corrected p -value \(\ge\) 0.05) and Cohen’s D (> 1 valued results discussed here – see Additional File 4 for all results).

C57BL/6 GC1, GC2, and GC3 content showed all TS comparisons were significantly different with very large Cohen’s D values (> > 1).

Significant difference was found for C57BL/6 GC and GG dinucleotides and junction dinucleotides between TS20 and TS26.

Codon usage for CD-1 was found significant between TS17, TS21, and TS22 for codon GGA (Gly).

Several usage comparisons between C57BL/6 and CD-1 revealed a significant difference. The most notable embryonic time periods were TS20 and TS22, potentially leading to differences during development at these time points.

Human versus mouse embryonic central nervous system usage change across Theiler stages for central nervous system samples

Studies have previously demonstrated that mouse and human brain tissues have selectively conserved codon usage across evolutionary development for CNS-specific genes [ 45 ]. Using Mouse Embryo CoCoPUTs and our previously generated website for human tissue-specific data from the TissueCoCoPUTs [ 28 ], we further evaluated similarities and differences among various usage metrics. We leveraged TissueCoCoPUTs and extracted human tissue usage data to match the analogous CNS categories used for the embryonic tissues (Additional File 3 ). We generated heatmaps, comparing mouse embryo usage to human usage, whereby if mouse usage is greater than human, the results will be greater than one (blue), and if human usage is greater, the result will be less than one (purple).

Figure  5 shows the mouse embryo-human ratio for different types of usage across each strain and its TS for CNS genes (GC content, dinucleotide, junction dinucleotide, codon, and codon pair usage are respectively associated with Panels A, B, C, D, and E).

Mouse Embryo vs Human Usage over Theiler stages for central nervous system genes. Each heatmap is subdivided on the y-axis by strain and Theiler stage. If a heatmap is blue, embryo usage outweighs human usage (> 1). If the heatmap is purple, human usage outweighs embryo usage (< 1). Panel A shows all strains have greater GC content than central nervous system human usage. Panel B usage values are all less than one signifying that human dinucleotide usage is greater than embryo usage, especially TA and CA usage. Junction dinucleotides that lead with T or A nucleotides show the biggest difference between human and embryo usage (Panel C). Codon usages are similar across all strains, with C57BL/6J most skewed away from human usage (Panel D). Panel E describes the codon pair usage (scaled) for all synonymous Alanine:Alanine (AlaAla) and Alanine:Arginine (AlaArg) codon pairs. This heatmap shows a dramatic increase in human usage for GCAGCT (AlaAla)

Interestingly, human outweighed mouse embryo in all CNS usage categories, except for GC content.

The biggest mouse contribution comes from GC2 usage, suggesting that GC content may be more integral towards codon mouse development.

Human dinucleotide, junction dinucleotide, codon, and especially codon pair usage is very similar to mouse embryo, supporting mouse embryo usage values as good experimental representatives independent of the strain for CNS genes.

It has been shown that dinucleotide CG may impact mouse embryology through the movement of transposable elements and site methylation [ 46 ]. Within the 5’ untranslated region of LINE1 transposon (L1) promotors, day 0 (d0) showed very little methylation of CG dinucleotide sites, but by day 21 CG sites were more than 80% methylated. CG usage peaks near YY1 transcription factor binding sites have been shown to potentially direct DNA methylation towards L1 promotors, reducing their impact during development [ 46 ]. Both human and mouse embryo show a strong preference for dinucleotide CA, suggesting the location of the dinucleotide, at a codon junction versus elsewhere, may influence its usage and how it changes over time. Dinucleotide CA may play a secondary role in controlling the translation rate throughout fetal development.

Other studies have demonstrated an underrepresentation of certain dinucleotides in genes associated with disease [ 40 ]. For example, genes associated with neurodegeneration were shown to have less than expected dinucleotide CG, GT, and TA usage, positive correlations with CC, CG, CT, GC, and GG, and negative correlations with AA, AT, GA, TA, and TT [ 47 ]. Alqahtani et al. (2021) speculated that neurodegeneration-associated genes may have originated from viruses that eventually gain functionality, since humans and viruses share underrepresented dinucleotides CG, TA, and GT. Suppression of these dinucleotides may contribute to selection pressure, degradation, and/or methylation and deamination [ 47 ]. Within our CNS data, we found similar expectations for the C57BL/6, C57BL/6J, and CD-1 mouse strains. The human CNS dinucleotide usage data revealed an increase for CG, TA, and GT dinucleotides, especially TA—as it is one of the preferred dinucleotides. Identification and location of dinucleotides may be of importance in search of characteristics shared between mouse embryo and human and their relation to congenital diseases. Mouse Embryo CoCoPUTs may provide aid to clinical researchers in need of mouse models with specific GC criteria or target specific information per stage as well as many other uses [ 13 ].

Synonymous codon usage, specifically leucine and arginine, has also been shown to reduce embryonic mouse cell proliferation but not affect stem cell pluripotency [ 48 ]. A decrease in the production of these synonymous codons is directly related to a decrease in protein translation. Leca et al. [ 49 ] revealed a neurodevelopmental phenotype produced via differential synonymous codon usage that dramatically altered protein production leading to homozygous lethality [ 49 ]. Future studies evaluating different mouse strains, especially developmental studies spanning multiple embryonic stages or strain targeting for pre-clinical testing of therapeutics, should be aware of the impact of these usage differences. These findings are critical for understanding the relationship between these usage types and embryonic development, and provide the necessary biological context for future studies looking to elucidate disease-gene expression relationships across development.

Mouse Embryo CoCoPUTs provides researchers with unique access to transcriptomic-weighted mouse embryo usage data that can be compared between strains, tissues, and stages [ 13 ]. Any deviations in patterns of usage preferences provided on website may be indicators of developmental abnormalities and may be useful guiding a generation of novel disease predictors. Limitations of this resource are its inability to run calculations within the website (i.e., average, variance), difficulty in making comparisons over several embryonic stages, and comparisons to other species. Future goals of the Mouse Embryo CoCoPUTs website are to implement new features to overcome these limitations, update regularly with new samples, and add useful comparison calculations like relative synonymous codon usage, and expected number of codons (Enc) and expected number of codon pairs (Encp) to facilitate broader species comparisons.

Mouse Embryo CoCoPUTs, a novel resource, holds the potential to facilitate investigations into tissue-, stage-, or strain-specific biotherapeutic development, genetic engineering, and genetic disease prediction [ 13 ]. Here, we describe a tool that combines gene sequence data and murine tissue- and stage-specific gene counts to create transcriptomic-weighted GC, dinucleotide, junction dinucleotide, codon, and codon pair usage across murine strains, tissues, and stages. The homepage of Mouse Embryo CoCoPUTs gives the user the option to query the usage website via murine strain, tissue, and stage (Table  1 ), download original transcriptome-weighted usage files, and a ‘Help’ tab that describes each search feature, different usage results (heatmaps, bar graphs, and tables), and methods for related calculations. Mouse Embryo CoCoPUTs can be used to identify relationships among embryonic strains, stages, and human usage ( 13 ). Across various metrics of usage, mouse embryo exhibited unique patterns and similarities across different strains C57BL/6, C57BL/6J, and CD-1.

Availability of data and materials

The raw datasets generated and analyzed during the current study are available for download from Mouse Embryo CoCoPUTs.

Abbreviations

• Theiler stage
• Embryonic day

Codon and codon pair usage tables

Central nervous system

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Acknowledgements

We gratefully acknowledge all data contributors, i.e., the Authors and their Originating laboratories responsible for obtaining the specimens, and their Submitting laboratories for generating the genetic sequence and metadata, on which this research is based. We also want to thank Nigam H. Padhiar for his helpful discussions and pointers.

This work was supported by funds from the Center for Biologics Evaluation and Research, US Food and Drug Administration operating funds.

Author information

Sarah E. Fumagalli, Sean Smith and Tigran Ghazanchyan have contributed equally.

Authors and Affiliations

Hemostasis Branch 1, Division of Hemostasis, Office of Plasma Protein Therapeutics CMC, Office of Therapeutic Products, Center for Biologics Evaluation and Research (CBER), US Food and Drug Administration (FDA), Silver Spring, MD, USA

Sarah E. Fumagalli, Douglas Meyer, Ryan C. Hunt, Brian Lin & Chava Kimchi-Sarfaty

High-performance Integrated Virtual Environment (HIVE), Office of Biostatistics and Pharmacovigilance (OBPV), Center for Biologics Evaluation and Research (CBER), US Food and Drug Administration (FDA), Silver Spring, MD, USA

Sean Smith, Tigran Ghazanchyan, Rahul Paul, Collin Campbell, Luis Santana-Quintero & Anton Golikov

Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children’s Hospital and Harvard Medical School, Boston, MA, USA

Department of Statistics, University of Connecticut, Storrs, CT, USA

Department of Biological, Geological and Environmental Sciences, Center for Gene Regulation in Health and Disease, Cleveland State University, Cleveland, OH, USA

Anton A. Komar

Rockville, USA

Michael DiCuccio

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Contributions

S.E.F: Formal Analysis, Methodology, Visualization, Writing-original draft, review & editing. S.S.: Data Curation, Methodology, Writing-review & editing. T.G.: Software & Writing-review & editing. D.M.: Conceptualization, Investigation, Writing-review & editing. R.P.: Data Curation, Validation. C.C.: Data Curation, Validation. B.L.: Writing-review & editing, L.S-Q.: Data Curation, Validation, Supervision. A.G.: Data Curation, Validation. J.I.: Investigation, Writing-review & editing. H.B.: Investigation, Writing-review & editing. A.A.K.: Investigation, Writing-review & editing. R.C.H.: Writing-review & editing. M.D.: Investigation. C.K-S.: Conceptualization, Funding acquisition, Writing-review & editing, Supervision.

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Correspondence to Chava Kimchi-Sarfaty .

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Fumagalli, S.E., Smith, S., Ghazanchyan, T. et al. Mouse embryo CoCoPUTs: novel murine transcriptomic-weighted usage website featuring multiple strains, tissues, and stages. BMC Bioinformatics 25 , 294 (2024). https://doi.org/10.1186/s12859-024-05906-3

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DOI : https://doi.org/10.1186/s12859-024-05906-3

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