@article{ac553df19a39492488e3d58910fea75f,
title = "Control-independent mosaic single nucleotide variant detection with DeepMosaic",
abstract = "Mosaic variants (MVs) reflect mutagenic processes during embryonic development and environmental exposure, accumulate with aging and underlie diseases such as cancer and autism. The detection of noncancer MVs has been computationally challenging due to the sparse representation of nonclonally expanded MVs. Here we present DeepMosaic, combining an image-based visualization module for single nucleotide MVs and a convolutional neural network-based classification module for control-independent MV detection. DeepMosaic was trained on 180,000 simulated or experimentally assessed MVs, and was benchmarked on 619,740 simulated MVs and 530 independent biologically tested MVs from 16 genomes and 181 exomes. DeepMosaic achieved higher accuracy compared with existing methods on biological data, with a sensitivity of 0.78, specificity of 0.83 and positive predictive value of 0.96 on noncancer whole-genome sequencing data, as well as doubling the validation rate over previous best-practice methods on noncancer whole-exome sequencing data (0.43 versus 0.18). DeepMosaic represents an accurate MV classifier for noncancer samples that can be implemented as an alternative or complement to existing methods.",
keywords = "mosaic variants, mutagenic variants, Nucleotide, DeepMosaic, Embryonic development, Genomic analysis, machine learning, mutation",
author = "Xiaoxu Yang and Xin Xu and Breuss, {Martin W.} and Danny Antaki and Ball, {Laurel L.} and Changuk Chung and Jiawei Shen and Chen Li and George, {Renee D.} and Yifan Wang and Taejeong Bae and Yuhe Cheng and Alexej Abyzov and Liping Wei and Alexandrov, {Ludmil B.} and Sebat, {Jonathan L.} and {NIMH Brain Somatic Mosaicism Network} and Dan Averbuj and Subhojit Roy and Eric Courchesne and Huang, {August Y.} and Alissa D{\textquoteright}Gama and Caroline Dias and Walsh, {Christopher A.} and Javier Ganz and Michael Lodato and Michael Miller and Pengpeng Li and Rachel Rodin and Robert Hill and Sara Bizzotto and Sattar Khoshkhoo and Zinan Zhou and Alice Lee and Alison Barton and Alon Galor and Chong Chu and Craig Bohrson and Doga Gulhan and Eduardo Maury and Elaine Lim and Euncheon Lim and Giorgio Melloni and Isidro Cortes and Jake Lee and Joe Luquette and Lixing Yang and Maxwell Sherman and Michael Coulter and Minseok Kwon and Park, {Peter J.} and Rebeca Borges-Monroy and Semin Lee and Sonia Kim and Soo Lee and Vinary Viswanadham and Yanmei Dou and Chess, {Andrew J.} and Attila Jones and Chaggai Rosenbluh and Schahram Akbarian and Ben Langmead and Jeremy Thorpe and Sean Cho and Andrew Jaffe and Apua Paquola and Weinberger, {Daniel R.} and Jennifer Erwin and Jooheon Shin and Michael McConnell and Richard Straub and Rujuta Narurkar and Yeongjun Jang and Cindy Molitor and Mette Peters and Gage, {Fred H.} and Meiyan Wang and Patrick Reed and Sara Linker and Alexander Urban and Bo Zhou and Xiaowei Zhu and Amero, {Aitor S.} and David Juan and Inna Povolotskaya and Irene Lobon and Moruno, {Manuel S.} and Perez, {Raquel G.} and Tomas Marques-Bonet and Eduardo Soriano and Gary Mathern and Diane Flasch and Trenton Frisbie and Huira Kopera and Jeffrey Kidd and John Moldovan and Moran, {John V.} and Kenneth Kwan and Ryan Mills and Sarah Emery and Weichen Zhou and Xuefang Zhao and Aakrosh Ratan and Alexandre Jourdon and Vaccarino, {Flora M.} and Liana Fasching and Nenad Sestan and Sirisha Pochareddy and Soraya Scuderi and Gleeson, {Joseph G.}",
year = "2023",
month = jun,
doi = "10.1038/s41587-022-01559-w",
language = "English",
volume = "41",
pages = "870--877",
journal = "Nature Biotechnology",
issn = "1087-0156",
publisher = "Nature Research",
number = "6",
}
