Helmsman: fast and efficient mutation signature analysis for massive sequencing datasets

• Published in: BMC genomics Vol. 19; no. 1; pp. 845 - 5
• Main Authors: Carlson, Jedidiah, Li, Jun Z., Zöllner, Sebastian
• Format: Journal Article
• Language: English
• Published: London BioMed Central 28.11.2018; BioMed Central Ltd; Springer Nature B.V; BMC
• Subjects: Analysis; Animal Genetics and Genomics; Bioinformatics; Biomedical and Life Sciences; Cancer; Cancer genetics; Cancer genomics; Computer memory; Computer programs; Datasets; DNA Mutational Analysis - methods; DNA repair; Etiology; Gene mutation; Gene sequencing; Genetic algorithms; Genomes; Genomics; Genotype & phenotype; High-Throughput Nucleotide Sequencing - methods; Human and rodent genomics; Life Sciences; Microarrays; Microbial Genetics and Genomics; Mutation; Mutation - genetics; Mutational signatures; Parameter estimation; Plant Genetics and Genomics; Proteomics; Python; Reproducibility of Results; Sample size; Scientific software; Signature analysis; Signatures; Single nucleotide polymorphisms; Single nucleotide variants; Software; Software development tools; Mutational signatures; Single nucleotide variants; Cancer genomics; Python
• ISSN: 1471-2164; 1471-2164
• DOI: 10.1186/s12864-018-5264-y

Background The spectrum of somatic single-nucleotide variants in cancer genomes often reflects the signatures of multiple distinct mutational processes, which can provide clinically actionable insights into cancer etiology. Existing software tools for identifying and evaluating these mutational signatures do not scale to analyze large datasets containing thousands of individuals or millions of variants. Results We introduce Helmsman, a program designed to perform mutation signature analysis on arbitrarily large sequencing datasets. Helmsman is up to 300 times faster than existing software. Helmsman’s memory usage is independent of the number of variants, resulting in a small enough memory footprint to analyze datasets that would otherwise exceed the memory limitations of other programs. Conclusions Helmsman is a computationally efficient tool that enables users to evaluate mutational signatures in massive sequencing datasets that are otherwise intractable with existing software. Helmsman is freely available at https://github.com/carjed/helmsman .