title: In-depth comparison of somatic point mutation callers based on different tumor next-generation sequencing depth data.
abstract: Four popular somatic single nucleotide variant (SNV) calling methods (Varscan, SomaticSniper, Strelka and MuTect2) were carefully evaluated on the real whole exome sequencing (WES, depth of ~50X) and ultra-deep targeted sequencing (UDT-Seq, depth of ~370X) data. The four tools returned poor consensus on candidates (only 20% of calls were with multiple hits by the callers). For both WES and UDT-Seq, MuTect2 and Strelka obtained the largest proportion of COSMIC entries as well as the lowest rate of dbSNP presence and high-alternative-alleles-in-control calls, demonstrating their superior sensitivity and accuracy. Combining different callers does increase reliability of candidates, but narrows the list down to very limited range of tumor read depth and variant allele frequency. Calling SNV on UDT-Seq data, which were of much higher read-depth, discovered additional true-positive variations, despite an even more tremendous growth in false positive predictions. Our findings not only provide valuable benchmark for state-of-the-art SNV calling methods, but also shed light on the access to more accurate SNV identification in the future.
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Key Laboratory of Psychotic Disorders (No.13dz2260500), Shanghai Jiao Tong University, Shanghai, 200030, China.|Gordon Life Science Institute, Boston, Massachusetts, 02478, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Cai
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Key Laboratory of Psychotic Disorders (No.13dz2260500), Shanghai Jiao Tong University, Shanghai, 200030, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yuan
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Key Laboratory of Psychotic Disorders (No.13dz2260500), Shanghai Jiao Tong University, Shanghai, 200030, China.|Institute of Biliary Tract Disease, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Key Laboratory of Psychotic Disorders (No.13dz2260500), Shanghai Jiao Tong University, Shanghai, 200030, China.|Women's Hospital School Of Medicine Zhejiang University, Hangzhou, 310006, China.
authors.forename: Lin
authors.initials: L
authors.lastname: He
authors.affiliation: Gordon Life Science Institute, Boston, Massachusetts, 02478, USA.|Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah, 21589, Saudi Arabia.
authors.forename: Kuo-Chen
authors.initials: KC
authors.lastname: Chou
mesh_terms: D000483:Alleles; D005260:Female; D005787:Gene Frequency; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000235:genetics*; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide