COSIGT: population-scalable genotyping of complex loci from low-coverage sequencing data using pangenome graphs

Genome biology 2026 Open access

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Authors: Davide Bolognini, Andrea Guarracino, Chiara Paleni, Thomas Sumner Dudley, Licia Iacoviello, Alessandro Raveane, Peter H. Sudmant, Erik Garrison, Nicole Soranzo
DOI: 10.1186/s13059-026-04242-4
Cited by: 1
References: 49

Abstract

Pangenome graphs capture extensive structural diversity, but resolving complex loci from shallow sequencing remains challenging, particularly when samples are of low quality such as in ancient DNA. We introduce COSIGT (COsine SImilarity-based GenoTyper), which assigns diploid genotypes by matching read-depth distributions to haplotype paths via cosine similarity. Because this metric evaluates relative coverage profiles rather than absolute read counts, COSIGT substantially outperforms existing likelihood-based tools at low coverage (1-2X). We demonstrate scalability to thousands of modern and ancient genomes, enabling robust, population-scale analyses of complex variation directly from low-coverage datasets.

Fields of Study & Subjects

Genetic Associations and Epidemiology Genomics and Rare Diseases Genetic Mapping and Diversity in Plants and Animals

Publication details

Journal / source
Genome biology
Publisher
Springer Science and Business Media LLC
Volume
27
Issue
1
Publication date
8 September 2026
Language
EN