title: MosaicHunter: accurate detection of postzygotic single-nucleotide mosaicism through next-generation sequencing of unpaired, trio, and paired samples.
abstract: Genomic mosaicism arising from postzygotic mutations has long been associated with cancer and more recently with non-cancer diseases. It has also been detected in healthy individuals including healthy parents of children affected with genetic disorders, highlighting its critical role in the origin of genetic mutations. However, most existing software for the genome-wide identification of single-nucleotide mosaicisms (SNMs) requires a paired control tissue obtained from the same individual which is often unavailable for non-cancer individuals and sometimes missing in cancer studies. Here, we present MosaicHunter (http://mosaichunter.cbi.pku.edu.cn), a bioinformatics tool that can identify SNMs in whole-genome and whole-exome sequencing data of unpaired samples without matched controls using Bayesian genotypers. We evaluate the accuracy of MosaicHunter on both simulated and real data and demonstrate that it has improved performance compared with other somatic mutation callers. We further demonstrate that incorporating sequencing data of the parents can be an effective approach to significantly improve the accuracy of detecting SNMs in an individual when a matched control sample is unavailable. Finally, MosaicHunter also has a paired mode that can take advantage of matched control samples when available, making it a useful tool for detecting SNMs in both non-cancer and cancer studies.
authors.affiliation: Center for Bioinformatics, State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, People's Republic of China.|National Institute of Biological Sciences, Beijing 102206, People's Republic of China.
authors.forename: August Yue
authors.initials: AY
authors.lastname: Huang
authors.affiliation: Center for Bioinformatics, State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, People's Republic of China.|School of Life Sciences, Tsinghua-Peking Joint Center for Life Sciences, Tsinghua University, Beijing 100084, People's Republic of China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Center for Bioinformatics, State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, People's Republic of China.|Peking-Tsinghua Center for Life Sciences, Beijing, People's Republic of China.|Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, People's Republic of China.
authors.forename: Adam Yongxin
authors.initials: AY
authors.lastname: Ye
authors.affiliation: Center for Bioinformatics, State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, People's Republic of China.|National Institute of Biological Sciences, Beijing 102206, People's Republic of China.
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Dou
authors.affiliation: Center for Bioinformatics, State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, People's Republic of China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Yan
authors.affiliation: Center for Bioinformatics, State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, People's Republic of China.
authors.forename: Xiaoxu
authors.initials: X
authors.lastname: Yang
authors.affiliation: Peking University First Hospital, Peking University, Beijing 100034, People's Republic of China.
authors.forename: Yuehua
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Center for Bioinformatics, State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, People's Republic of China.
authors.forename: Liping
authors.initials: L
authors.lastname: Wei
mesh_terms: D000328:Adult; D000465:Algorithms; D001499:Bayes Theorem; D019985:Benchmarking; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002648:Child; D066264:Datasets as Topic; D004831:Epilepsies, Myoclonic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D059472:Exome; D005260:Female; D005838:Genotype; D006579:Heterozygote; D059014:High-Throughput Nucleotide Sequencing; D006720:Homozygote; D006801:Humans; D040582:Inheritance Patterns; D008297:Male; D009030:Mosaicism; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D012984:Software