RT Journal Article
SR Electronic
T1 Detecting and phasing minor single-nucleotide variants from long-read sequencing data
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.09.25.314252
DO 10.1101/2020.09.25.314252
A1 Zhixing Feng
A1 Jose Clemente
A1 Brandon Wong
A1 Eric E. Schadt
YR 2020
UL http://biorxiv.org/content/early/2020/09/27/2020.09.25.314252.abstract
AB Cellular genetic heterogeneity is common in many biological conditions including cancer, microbiome, co-infection of multiple pathogens. Detecting and phasing minor variants, which is to determine whether multiple variants are from the same haplotype, play an instrumental role in deciphering cellular genetic heterogeneity, but are still difficult because of technological limitations. Recently, long-read sequencing technologies, including those by Pacific Biosciences and Oxford Nanopore, have provided an unprecedented opportunity to tackle these challenges. However, high error rates make it difficult to take full advantage of these technologies. To fill this gap, we introduce iGDA, an open-source tool that can accurately detect and phase minor single-nucleotide variants (SNVs), whose frequencies are as low as 0.2%, from raw long-read sequencing data. We also demonstrated that iGDA can accurately reconstruct haplotypes in closely-related strains of the same species (divergence ≥ 0.011%) from long-read metagenomic data. Our approach, therefore, presents a significant advance towards the complete deciphering of cellular genetic heterogeneity.Competing Interest StatementE.E.S. is on the scientific advisory board of Pacific Biosciences.