Submitting Your Manuscript and Navigating Peer Review

The moment you submit a manuscript, your work enters a social and institutional process that is simultaneously technical, rhetorical, and interpersonal. Peer review — despite its well-documented limitations — remains the primary mechanism by which the scientific community validates and integrates new knowledge. Understanding how this process works, what editors and reviewers are looking for, and how to respond constructively to feedback are skills that distinguish researchers who publish regularly from those who find the process opaque and discouraging. This chapter walks through the full arc of manuscript submission, from preparing your files to responding to reviewers, and offers guidance on how to approach rejection productively.

Preparing Your Submission

Before you upload a single file, read the journal’s author guidelines in their entirety. This advice sounds obvious, but a substantial proportion of manuscripts are returned to authors — or rejected at desk — simply because they do not conform to the journal’s stated requirements. Author guidelines specify the accepted manuscript formats (Word, LaTeX, PDF), the permitted length in words or pages, the required sections, the reference style, and the conventions for figures and tables. Some journals require that figures be submitted as separate high-resolution files in specific formats (TIFF at 300 dpi, EPS for line art); others accept figures embedded in the manuscript document during initial submission. Some journals require structured abstracts with explicit subheadings; others require unstructured prose abstracts of a specific word limit.

Figures deserve particular attention. Journals that publish in print or high-quality digital formats often have exacting requirements for image resolution, color mode, and font sizes within figures. A figure that looks acceptable on screen may fail to meet print specifications. Confirm that all panels are labeled consistently, that all abbreviations in figure legends are defined, and that all figures are cited in the main text in numerical order. Supplementary materials — additional datasets, extended methods, supplementary figures and tables — should be prepared according to the journal’s specific conventions, as these vary considerably.

Before submission, conduct a final author-list check. Confirm that all contributors meet the journal’s authorship criteria (typically based on the ICMJE criteria: conception, execution, critical revision, and approval of the final version ICMJE 2023), that the order of authors has been discussed and agreed upon, and that all authors have read and approved the final version. Confirm that all authors have disclosed any conflicts of interest, financial relationships, or competing interests as required by the journal’s policy. Many journals now also require registration of author ORCID identifiers, which helps disambiguate authors and links publications to researchers’ professional records.

The Cover Letter

The cover letter is the first thing an editor reads and, for many editors, the document that determines whether a manuscript proceeds to external review or is desk-rejected. A well-written cover letter does not simply repeat the abstract; it frames the work for the editor, explains why it belongs in this particular journal, and addresses any issues the editor might otherwise raise.

Begin by stating the title and type of manuscript (original research article, review, brief communication) and naming the corresponding author. In the opening paragraph, make the case for significance: what is the problem your work addresses, why does it matter, and what is the key advance your findings represent? This framing should be tailored to the journal’s scope and readership — the way you pitch a manuscript to a broad-audience journal like PLOS Biology differs from the way you pitch the same work to a specialized methods journal. The second paragraph should address fit more directly: why is this journal the right venue? If you are aware of recent articles in the journal that your work builds on or speaks to, citing them here signals genuine familiarity with the journal’s content.

Most journals invite authors to suggest potential reviewers and to identify individuals who should be excluded from review. Suggesting reviewers is an opportunity to direct your manuscript toward experts who have the specific expertise needed to evaluate your methods and interpret your findings. Name researchers who have published relevant work, have no conflict of interest with you or your co-authors, and are likely to provide a rigorous, fair assessment. Excluding reviewers is appropriate when a genuine conflict of interest exists — a direct competitor, a former mentor or student, or someone with whom you have an ongoing dispute — but should not be used as a tactic to avoid critical review. Editors are not obligated to follow either set of suggestions, and most handle them with appropriate judgment COPE 2017.

Submission Systems and Manuscript Tracking

The majority of journals now use web-based manuscript submission systems. Editorial Manager, developed by Aries Systems, and ScholarOne Manuscripts (formerly Manuscript Central), owned by Clarivate, are the two most widely deployed platforms in the life sciences and biomedical fields. Both systems guide you through a structured submission process: uploading files, entering metadata, confirming authorship and declarations, and typically a final PDF proof step in which the system assembles your files into a single document for editorial review.

When submitting, pay close attention to the metadata fields, including keywords, suggested subject classifications, and the manuscript type. These fields help editors route your manuscript to appropriate associate editors and help the journal’s search indexing. Keep a record of your submission confirmation number and the date of submission; you will need these for any follow-up correspondence. Most systems allow you to check the current status of your manuscript through a dashboard, which typically shows stages such as “With Editor,” “Under Review,” “Decision Pending,” and “Revision Requested.” These status indicators are useful but imprecise — “Under Review” may mean that one reviewer has agreed and is actively working, or that the editor is still searching for willing reviewers.

What Happens After Submission: Desk Rejection, External Review, and Timelines

After submission, your manuscript first reaches an editor — typically a handling editor or associate editor — who conducts an initial evaluation. At this stage, the editor assesses whether the manuscript meets the journal’s minimum criteria: scope, format, technical completeness, and preliminary significance. At highly selective journals, the majority of submissions are rejected at desk without external review, often within days to a few weeks Lauer & Krumholz 2017. A desk rejection is not necessarily a sign that the work is poor; it may simply mean the work does not fit the journal’s current priorities or is not considered of sufficient novelty for that particular venue.

If the manuscript passes the initial evaluation, it proceeds to external peer review. The editor identifies two or three experts in the relevant area, invites them to review, and must wait for them to accept before review can begin. Because reviewer invitations are often declined — reviewers are volunteers with their own competing demands — the time spent recruiting reviewers can be substantial. Once reviewers have agreed and submitted their reports, the editor synthesizes their assessments and makes a decision: accept, accept pending minor revisions, major revision, or reject.

Timelines vary widely. Some journals commit to first decisions within three to four weeks; others routinely take three to six months. Competitive fields with a small pool of experts create bottlenecks because the same researchers are invited to review for many journals simultaneously. If you have not received an acknowledgment of receipt within a week or a status update within the timeframe specified in the author guidelines, a polite inquiry to the editorial office is entirely appropriate Perkel 2020.

Types of Peer Review

The traditional model of single-blind peer review, in which reviewers know the authors’ identities but authors do not know the reviewers’ identities, remains the most common form in the life sciences. It is subject to well-documented biases: reviewers may be influenced by the prestige of the authors’ institutions, their familiarity with the authors’ prior work, or geographic and demographic biases that shape their assessments of novelty and significance.

Double-blind peer review, in which both authors and reviewers are anonymous to each other, attempts to mitigate some of these biases. Studies comparing double-blind to single-blind review have yielded mixed results, in part because reviewer anonymity is difficult to maintain in specialized fields where a small number of researchers are active on any given topic Bohannon 2013. Many journals now offer double-blind review as an option rather than a requirement, allowing authors to request it.

Open peer review — in which reviewers are identified to authors, or in which reviews are published alongside the article — is less common but growing, particularly among some open access journals. Proponents argue that transparency increases accountability and the quality of reviews; critics argue that named reviewers may be less willing to provide frank negative assessments of work by senior or influential researchers. Some journals, including eLife and EMBO Journal, publish reviewer reports alongside accepted articles as a way of making the review process more transparent to readers. Whatever form peer review takes, its purpose remains the same: to provide expert scrutiny that helps identify errors, strengthen interpretations, and assess the significance of new findings.

Interpreting Reviewer Comments

When a decision arrives, read it carefully before reacting emotionally. Editors’ decision letters vary in the degree to which they synthesize reviewers’ comments versus simply transmit them, but a key signal is the decision itself. An outright rejection with no invitation to revise means the editor does not wish to see a revised version at this journal and you should plan to submit elsewhere. A rejection with an invitation to submit a substantially revised version is a soft form of rejection; it means the editor sees potential but is not committing to reconsider without significant changes, and there is no guarantee that a revised version will be accepted. Major revision means the editor is interested but significant concerns must be addressed; this is a good outcome, though not yet an acceptance. Minor revision means the editor and reviewers are largely satisfied and you are very close to acceptance.

Reviewers’ reports can range from brief and unhelpful to extensive and detailed. A common response to critical reviews, especially for early-career researchers, is a sense of discouragement or defensiveness. This is entirely natural, but it is important to approach reviewer comments as a resource rather than an attack. Reviewers are typically experts who have read your manuscript carefully and identified genuine areas of confusion, weakness, or omission. Even when a comment seems unfair or based on a misreading of your methods, it may signal that your writing was insufficiently clear — a problem worth addressing regardless of whether you agree with the reviewer’s conclusion.

Read all reviewer comments before deciding how to respond. Sometimes what appear to be contradictory reviewer requests can be resolved through a careful revision that addresses the underlying concerns without satisfying the letter of conflicting demands. Identify which requests require new experiments or analyses, which require clarification of existing results, and which require revision of the prose. Communicate with your co-authors before beginning the revision, particularly if new experimental work is involved, since such work takes time and resources and all authors should be aligned on strategy.

Writing a Response Letter

The response letter — also called a point-by-point response or rebuttal letter — is submitted alongside your revised manuscript and serves two functions: it demonstrates to the editor that you have taken the reviewers’ comments seriously, and it provides a clear account of every change you have made and why. A well-written response letter can be as important as the revised manuscript itself, because editors often read the response letter before reviewing the manuscript to determine whether you have addressed the major concerns.

The standard format is to reproduce each reviewer comment in full, followed by your response. Begin each response with a brief acknowledgment of the concern, then explain what you did (added new data, revised a figure, rewrote a section) and why. If you disagree with a reviewer’s comment and have chosen not to comply, explain your reasoning calmly and provide evidence. Reviewers are not always right, and editors generally appreciate authors who can articulate a reasoned, evidence-based justification for not making a requested change. What editors and reviewers do not appreciate is a dismissive response that brushes aside concerns without engagement.

Keep your responses specific and respectful. Phrases like “we thank the reviewer for this insightful comment” have become somewhat formulaic, but genuine engagement with the substance of the review signals that you are a careful and responsive scientist COPE 2017. Indicate in the response letter where in the revised manuscript each change can be found — page number, line number, or section — so that editors and reviewers can quickly verify that you have made the changes you claim. Many authors also submit a version of the manuscript with tracked changes to make verification even easier; check whether the journal requires or recommends this.

Rejection and Resubmission Strategy

Rejection is a universal experience in science. Even highly accomplished researchers accumulate substantial rejection histories, and some of the most influential papers in biology were rejected by the first journal to which they were submitted. What distinguishes productive researchers is not freedom from rejection but the ability to respond to it efficiently and strategically.

When a manuscript is rejected, the first question to ask is whether the reviewers identified genuine scientific problems that need to be addressed before the paper is submitted anywhere else. If major concerns were raised about your experimental design, statistical analysis, or interpretation, it is in your long-term interest to address these before resubmitting, even though it takes time. Submitting a flawed manuscript to a succession of journals in the hope that one will accept it regardless of its problems is a short-term strategy with long-term costs to your reputation.

If the rejection was a matter of fit rather than scientific quality — the work was technically sound but outside the journal’s current priorities — you can often reformat the manuscript for the next journal relatively quickly. Identify the next journal on your list before you submit the first time, so that a rejection does not leave you without a plan. When reformatting for a new journal, take the time to genuinely tailor the introduction and discussion to the new journal’s scope and readership; editors can tell when an introduction has simply had its first paragraph updated while the rest was left unchanged.

Appeals — formal requests to the editor to reconsider a rejection — are appropriate in specific circumstances: when a reviewer has made a factual error that clearly drove the decision, when a reviewer’s comments suggest a fundamental misunderstanding of your methods, or when new information has emerged since submission that is directly relevant to the reviewers’ concerns. Appeals are not appropriate simply because you disagree with the editor’s assessment of novelty or significance. A clear, specific, evidence-based appeal written promptly after rejection has a reasonable chance of success; a frustrated appeal that argues for the importance of your work in general terms rarely does Lauer & Krumholz 2017.

The peer review process is imperfect, inconsistent, and at times frustrating. It is also the best system the scientific community has developed for collective quality control, and engaging with it skillfully — preparing carefully, responding constructively, and learning from every decision — is an essential part of scientific practice.