Abstract
The U2AF1 gene is a core part of mRNA splicing machinery and frequently contains somatic mutations that contribute to oncogenesis in myelodysplastic syndrome, acute myeloid leukemia, and other cancers. A change introduced in the GRCh38 version of the human reference build prevents detection of mutations in this gene, and others, by variant calling pipelines. This study describes the problem in detail and shows that a modified GRCh38 reference build with unchanged coordinates can be used to ameliorate the issue.
Highlights
From the Division of Oncology,* Department of Internal Medicine, the Siteman Cancer Center,y the McDonnell Genome Institute,z and the Department of Pathology and Immunology,** Washington University School of Medicine, St
The U2AF1 gene is a core part of mRNA splicing machinery and frequently contains somatic mutations that contribute to oncogenesis in myelodysplastic syndrome, acute myeloid leukemia, and other cancers
Splicing machinery that is frequently mutated in myelodysplastic syndrome (MDS) and other cancers.1e3 Though predominantly associated with hematopoietic cancers
Summary
A change introduced in the GRCh38 version of the human reference build prevents detection of mutations in this gene, and others, by variant calling pipelines. Sequencing reads from the MDS cohort were aligned to both masked and unmasked GRCh38 reference genomes using the BWA-MEM software package –strand-filter 1”.11 Data from TCGA acute myeloid leukemia samples were aligned using the same process, and somatic variants were called using an ensemble approach, described in detail in the CWL workflow at https://git.io/
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