Somalier: rapid relatedness estimation for cancer and germline studies using efficient genome sketches
Open Access
- 14 July 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Genome Medicine
- Vol. 12 (1), 1-9
- https://doi.org/10.1186/s13073-020-00761-2
Abstract
Background: When interpreting sequencing data from multiple spatial or longitudinal biopsies, detecting sample mix-ups is essential, yet more difficult than in studies of germline variation. In most genomic studies of tumors, genetic variation is detected through pairwise comparisons of the tumor and a matched normal tissue from the sample donor. In many cases, only somatic variants are reported, which hinders the use of existing tools that detect sample swaps solely based on genotypes of inherited variants. To address this problem, we have developed Somalier, a tool that operates directly on alignments and does not require jointly called germline variants. Instead, Somalier extracts a small sketch of informative genetic variation for each sample. Sketches from hundreds of germline or somatic samples can then be compared in under a second, making Somalier a useful tool for measuring relatedness in large cohorts. Somalier produces both text output and an interactive visual report that facilitates the detection and correction of sample swaps using multiple relatedness metrics. Results: We introduce the tool and demonstrate its utility on a cohort of five glioma samples each with a normal, tumor, and cell-free DNA sample. Applying Somalier to high-coverage sequence data from the 1000 Genomes Project also identifies several related samples. We also demonstrate that it can distinguish pairs of whole-genome and RNA-seq samples from the same individuals in the Genotype-Tissue Expression (GTEx) project. Conclusions: Somalier is a tool that can rapidly evaluate relatedness from sequencing data. It can be applied to diverse sequencing data types and genome builds and is available under an MIT license at.Funding Information
- National Institutes of Health (R41HG010126, R01HG009141, U24CA209999)
This publication has 16 references indexed in Scilit:
- Conpair: concordance and contamination estimator for matched tumor–normal pairsBioinformatics, 2016
- Second-generation PLINK: rising to the challenge of larger and richer datasetsGigaScience, 2015
- Toward better understanding of artifacts in variant calling from high-coverage samplesBioinformatics, 2014
- The Genotype-Tissue Expression (GTEx) projectNature Genetics, 2013
- Sensitive detection of somatic point mutations in impure and heterogeneous cancer samplesNature Biotechnology, 2013
- The variant call format and VCFtoolsBioinformatics, 2011
- Robust relationship inference in genome-wide association studiesBioinformatics, 2010
- The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing dataGenome Research, 2010
- The Sequence Alignment/Map format and SAMtoolsBioinformatics, 2009
- Fast and accurate short read alignment with Burrows–Wheeler transformBioinformatics, 2009