Efficient variant data preparation for Human Mutation manuscripts: Variants and phenotypes.

Abstract

Deputy Editor, Human Mutation Human Mutation's Author Guidelines provide details regarding structure, content, and standards that should be followed before a manuscript can be submitted for peer review. We work to be as accommodating as possible, but some of our requirements are nonnegotiable. For example, when genomic variants are reported, the journal requires that human genome variation society (HGVS) nomenclature recommendations are followed (den Dunnen et al., 2016). Beginning in March 2019, the journal required proof of HGVS nomenclature validation be provided upon submission. This requirement is detailed in the journal's online submission system and in our author guidelines (https://onlinelibrary.wiley.com/page/journal/10981004/homepage/forauthors.html#VerNomDNAVar). In addition, the guidelines require that variants reported in the manuscript be submitted to a public database before publication (e.g. the Global Variome shared LOVD [http://databases.lovd.nl/shared] or ClinVar [http://www.ncbi.nlm.nih.gov/clinvar]). Both of these requirements—accurate HGVS nomenclature and variant data deposition—have been compulsory for Human Mutation over the past 10 years. However, the exact “when” of compliance varies from submission to submission. In many cases, authors have not submitted their data to a public database before manuscript submission. This is not absolutely required for submitted manuscripts, and we understand that in some cases the effort to submit variant data to a database might appear to cause extra work and seem to be a waste of time, especially if the submission is not accepted for publication. However, the peer review and editorial evaluation process runs much more smoothly when both variant nomenclature confirmation and data submission are completed. Consequently, extra, often duplicative work may be required of the author after peer review and before publication. Therefore, we suggest that extra work could be avoided if variant data are handled in a different order: it is most helpful to submit variant data to a database first, before manuscript submission. Variant data submission to a database like ClinVar or LOVD will help authors to ensure that the HGVS nomenclature is correct. During database submission, the receiving database performs a quality check which often highlights problems with either variant reporting (non-HGVS descriptions) or missing data (e.g., phenotype, HPO terms). Besides sorting out these issues for the database submission, any corrections or additions to variant names have also to be incorporated into the submitted manuscript. After submission to a database, the author has the option to download the data in a format that supports easy reformatting to a Table or Figure for the manuscript to be submitted. Indeed, most databases provide options, through the database IDs assigned, to directly retrieve all data linked to the manuscript from the database. Providing a url to variant data in the database provides an alternative to Supporting Information files. A database such as the Global Variome shared LOVD allows retrieval of submitted data based on the DOI or PubMed ID assigned to the paper. For example, the data (variants and phenotypes) published by Carney, Wei, and Rizzo (2004) can be retrieved using the url https://databases.lovd.nl/shared/references/DOI:10.1002/humu.9262 (or http://databases.lovd.nl/shared/references/PMID:15241804). Our recommendation is made to reduce an author's work load, not to increase it. Furthermore, database submission is always a good idea. It ensures that variants and phenotype data become available as soon as possible, which is in the best interest of the patients, their families and for the scientific and medical communities. In fact, more and more top-level journals in human and medical genetics are requiring data deposition, to help their authors to be in compliance with open data/open research mandates. We encourage our authors and all researchers in this space to welcome this initiative toward open data.