Tarabichi, M;
Demeulemeester, J;
Verfaillie, A;
Flanagan, AM;
Van Loo, P;
Konopka, T;
(2021)
A pan-cancer landscape of somatic mutations in non-unique regions of the human genome.
Nature Biotechnology
, 39
pp. 1589-1596.
10.1038/s41587-021-00971-y.
Preview |
Text
Tarabachi Accepted Manuscript.pdf - Accepted Version Download (3MB) | Preview |
Abstract
A substantial fraction of the human genome displays high sequence similarity with at least one other genomic sequence, posing a challenge for the identification of somatic mutations from short-read sequencing data. Here we annotate genomic variants in 2,658 cancers from the Pan-Cancer Analysis of Whole Genomes (PCAWG) cohort with links to similar sites across the human genome. We train a machine learning model to use signals distributed over multiple genomic sites to call somatic events in non-unique regions and validate the data against linked-read sequencing in an independent dataset. Using this approach, we uncover previously hidden mutations in ~1,700 coding sequences and in thousands of regulatory elements, including in known cancer genes, immunoglobulins and highly mutated gene families. Mutations in non-unique regions are consistent with mutations in unique regions in terms of mutation burden and substitution profiles. The analysis provides a systematic summary of the mutation events in non-unique regions at a genome-wide scale across multiple human cancers.
Archive Staff Only
 |
View Item |
