Somatic mutation detection: a critical evaluation through simulations and reanalyses in oaksuse asterix (*) to get italics

Sylvain Schmitt, Thibault Leroy, Myriam Heuertz, Niklas TysklindPlease use the format "First name initials family name" as in "Marie S. Curie, Niels H. D. Bohr, Albert Einstein, John R. R. Tolkien, Donna T. Strickland"

2022

<p style="text-align: justify;">1. Mutation, the source of genetic diversity, is the raw material of evolution; however, the mutation process remains understudied, especially in plants. Using both a simulation and reanalysis framework, we set out to explore and demonstrate the improved performance of variant callers developed for cancer research compared to single nucleotide polymorphism (SNP) callers in detecting de novo somatic mutations.</p> <p style="text-align: justify;">2. In an in silico experiment, we generated Illumina-like sequence reads spiked with simulated mutations at different allelic fractions to compare the performance of seven commonly-used variant callers to recall them. More empirically, we then reanalyzed two of the largest datasets available for plants, both developed for identifying within-individual variation in long-lived pedunculate oaks.</p> <p style="text-align: justify;">3. Based on the in silico experiment, variant callers developed for cancer research outperform SNP callers regarding plant mutation recall and precision, especially at low allele frequency. Such variants at low allelic fractions are typically expected for within-individual de novo plant mutations, which initially appear in single cells. Reanalysis of published oak data with Strelka2, the best-performing caller based on our simulations, identified up to 3.4x more candidate somatic mutations than reported in the original studies.</p> <p style="text-align: justify;">4. Our results advocate the use of cancer research callers to boost de novo mutation research in plants, and to reconcile empirical reports with theoretical expectations.</p>

https://www.ncbi.nlm.nih.gov/bioproject/327502, https://www.ebi.ac.uk/ena/browser/view/PRJEB8388, https://doi.org/10.5281/zenodo.7274868, https://doi.org/10.5281/zenodo.7274872You should fill this box only if you chose 'All or part of the results presented in this preprint are based on data'. URL must start with http:// or https://

Somatic mutations ; Oak ; Variant caller performance ; Mutation spectra ; Strelka2 ; GATK

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Bioinformatics, Plants

Christophe Plomion [christophe.plomion@inrae.fr] No need for them to be recommenders of PCI Genomics. Please do not suggest reviewers for whom there might be a conflict of interest. Reviewers are not allowed to review preprints written by close colleagues (with whom they have published in the last four years, with whom they have received joint funding in the last four years, or with whom they are currently writing a manuscript, or submitting a grant proposal), or by family members, friends, or anyone for whom bias might affect the nature of the review - see the code of conduct

Emanuel Schmid-Siegert [emanuel.schmid-siegert@unil.ch]e.g. John Doe [john@doe.com]

2022-04-28 13:24:19

Nicolas Bierne

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