Identification of Clonal Hematopoiesis Driver Mutations through In Silico Saturation Mutagenesis.

ABSTRACT: Clonal hematopoiesis (CH) is a phenomenon of clonal expansion of hematopoietic stem cells driven by somatic mutations affecting certain genes. Recently, CH has been linked to the development of hematologic malignancies, cardiovascular diseases, and other conditions. Although the most frequently mutated CH driver genes have been identified, a systematic landscape of the mutations capable of initiating this phenomenon is still lacking. In this study, we trained machine learning models for 12 of the most recurrent CH genes to identify their driver mutations. These models outperform expert-curated rules based on prior knowledge of the function of these genes. Moreover, their application to identify CH driver mutations across almost half a million donors of the UK Biobank reproduces known assoc

SUBMITTER: Demajo S 

PROVIDER: S-EPMC11372364 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature