Year: 2019
Type: article
Abstract: Linked-read sequencing enables greatly improves haplotype assembly over standard paired-end analysis. The detection of mosaic single-nucleotide variants benefits from haplotype assembly when the model is informed by the mapping between constituent reads and linked reads. Samovar evaluates haplotype-discordant reads identified through linked-read sequencing, thus enabling phasing and mosaic variant detection across the entire genome. Samovar trains a random forest model to score candidate sites using a dataset that considers read quality, phasing, and linked-read characteristics. Samovar calls mosaic single-nucleotide variants (SNVs) within a single sample with accuracy comparable with what previously required trios or matched tumor/normal pairs and outperforms single-sample mosaic variant callers at minor allele frequency 5%-50% with at least 30X coverage. Samovar finds somatic variants in both tumor and normal whole-genome sequencing from 13 pediatric cancer cases that can be corroborated with high recall with whole exome sequencing. Samovar is available open-source at https://github.com/cdarby/samovar under the MIT license.
Source: iScience
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,000
Funders: National Science Foundation, Nationwide Children's Hospital, Children's Hospital Foundation, Maryland Advanced Research Computing Center, National Institutes of Health, National Institute of Mental Health, National Human Genome Research Institute, National Cancer Institute, National Institute of General Medical Sciences
Awards: G2901194989, Somatic variant calling and phasing using colored de Bruijn graphs in heterogeneous tumors, G4298445392, G4570290924, CAREER: Algorithms for single molecule sequence analysis, Computational Gene Modeling and Genome Sequence Assembly, G728701865, G9000020123, G9000133668, G9000184996, G9000191379, G9000330195, G90618688
OpenAlex ID: W2946895064