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bioRxiv · 10.1101/343970

GLnexus: joint variant calling for large cohort sequencing

Lin, M. F.·Rodeh, O.·Penn, J.·Bai, X.·Krasheninina, O.·Salerno, W. J.·Reid, J. G.
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Abstract

As ever-larger cohorts of human genomes are collected in pursuit of genotype/phenotype associations, sequencing informatics must scale up to yield complete and accurate genotypes from vast raw datasets. Joint variant calling, a data processing step entailing simultaneous analysis of all participants sequenced, exhibits this scaling challenge acutely. We present GLnexus (GL, Genotype Likelihood), a system for joint variant calling designed to scale up to the largest foreseeable human cohorts. GLnexus combines scalable joint calling algorithms with a persistent database that grows efficiently as additional participants are sequenced. We validate GLnexus using 50,000 exomes to show it produces comparable or better results than existing methods, at a fraction of the computational cost with better scaling. We provide a standalone open-source version of GLnexus and a DNAnexus cloud-native deployment supporting very large projects, which has been employed for cohorts of >240,000 exomes and >22,000 whole-genomes.

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Lin, M. F., Rodeh, O., Penn, J., Bai, X., Krasheninina, O., Salerno, W. J., Reid, J. G.. 2018-06-11. GLnexus: joint variant calling for large cohort sequencing. https://doi.org/10.1101/343970

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