Various approaches to calling single-nucleotide variants (SNVs) or insertion-or-deletion (indel) mutations have been developed based on next-generation sequencing (NGS). However, most of them are dedicated to a particular type of mutation, e.g. germline SNVs in normal cells, somatic SNVs in cancer/tumor cells, or indels only. In the literature, efficient and integrated callers for both germline and somatic SNVs/indels have not yet been extensively investigated.

SNVSniffer is an efficient and integrated caller identifying both germline and somatic SNVs/indels from NGS data. In this algorithm, we propose the use of Bayesian probabilistic models to identify SNVs and investigate a multiple ungapped alignment approach to call indels. For germline variant calling, we model allele counts per site to follow a multinomial conditional distribution. For somatic variant calling, we rely on paired tumor-normal pairs from identical individuals and introduce a hybrid subtraction and joint sample analysis approach by modeling tumor-normal allele counts per site to follow a joint multinomial conditional distribution. A comprehensive performance evaluation has been conducted using a diversity of variant calling benchmarks. For germline variant calling, SNVSniffer demonstrates highly competitive accuracy with superior speed in comparison with the state-of-the-art FaSD, GATK and SAMtools. For somatic variant calling, our algorithm achieves comparable or even better accuracy, at fast speed, than the leading VarScan2, SomaticSniper, JointSNVMix2 and MuTect.

SNVSniffer consists of five components: a SNP and indel caller, a somatic variant and indel caller from normal-tumour sample pairs, an Illumina-like next-generation sequencing (NGS) read simulator of SNP calling, an Illumina-like NGS normal-tumour sample simulator for somatic mutation calling, and a VCF-based evaluation algorithm for germline and somatic SNVs.


We welcome any feedback and bug reports for our caller. Only executable binaries are available for download at present and the source code will be availabe very soon. More details about the changes in this version are available at ChangeLog.


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Change Log


If any questions or improvements, please feel free to contact Liu, Yongchao.