Moss enables high sensitivity single-nucleotide variant calling from multiple bulk DNA tumor samples.
Nat Commun
; 12(1): 2204, 2021 04 13.
Article
em En
| MEDLINE
| ID: mdl-33850139
ABSTRACT
Intra-tumor heterogeneity renders the identification of somatic single-nucleotide variants (SNVs) a challenging problem. In particular, low-frequency SNVs are hard to distinguish from sequencing artifacts. While the increasing availability of multi-sample tumor DNA sequencing data holds the potential for more accurate variant calling, there is a lack of high-sensitivity multi-sample SNV callers that utilize these data. Here we report Moss, a method to identify low-frequency SNVs that recur in multiple sequencing samples from the same tumor. Moss provides any existing single-sample SNV caller the ability to support multiple samples with little additional time overhead. We demonstrate that Moss improves recall while maintaining high precision in a simulated dataset. On multi-sample hepatocellular carcinoma, acute myeloid leukemia and colorectal cancer datasets, Moss identifies new low-frequency variants that meet manual review criteria and are consistent with the tumor's mutational signature profile. In addition, Moss detects the presence of variants in more samples of the same tumor than reported by the single-sample caller. Moss' improved sensitivity in SNV calling will enable more detailed downstream analyses in cancer genomics.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
DNA de Neoplasias
/
Neoplasias Hepáticas
/
Nucleotídeos
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Nat Commun
Ano de publicação:
2021
Tipo de documento:
Article