MosaicHunter: a tool to detect postzygotic single-nucleotide mosaicism through next-generation sequencing of unpaired, trio, and paired samples

Finding postzygotic single-nucleotide mosaicisms

Genomic mosaicism is a biological phenomenon in which genetic alterations occurring during development or aging give rise to two or more cell populations with distinct genome sequences within one individual. Previous studies have discovered the role of mosaicism in multiple types of cancer as well as increasing number of 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.
To distinguish true mosaic sites from heterozygous and homozygous sites, and base-calling and alignment errors, we developed a new bioinformatics tool - MosaicHunter, which integrated a Bayesian genotyper and a series of stringent error filters for the identification of single-nucleotide mosaicisms (SNMs) from whole-genome or whole-exome sequencing data, with no requirement of paired control tissues from the same donor.

MosaicHunter is able to identify SNMs / somatic mutations in the absence of paired control tissues!
Most of the existing tools to identify SNMs needs to compare the sequencing data of the target sample against a control data sequenced from a paired sample of the same individual, such as tumor tissue sample vs normal tissue sample. However the application of these methods is unfeasible when paired control samples are unavailable, which is the case in most non-cancer studies and even in some cancer studies. MosaicHunter is designed to identify SNMs from whole-genome or whole-exome sequencing data of unpaired control-free samples.
MosaicHunter also has a "trio" mode and a "paired" mode that can take advantage of parental or matched control samples when available, which were able to further improve the accuracy of detecting SNMs.

Please Cite: Huang, A.Y., Zhang, Z., Ye, A.Y., Dou, Y., Yan, L., Yang, X., Zhang, Y., and Wei, L. (2017) MosaicHunter: accurate detection of postzygotic single-nucleotide mosaicism through next-generation sequencing of unpaired, trio, and paired samples. Nucleic Acids Res 45, e76.