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 a number 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. Here, we train high-quality machine-learning models for 12 of the most recurrent CH driver genes to identify their driver mutations. These models outperform an experimental base-editing approach and expert-curated rules based on prior knowledge of the function of these genes. Moreover, their application to identify CH driver mutations across almost

SUBMITTER: Demajo S 

PROVIDER: S-EPMC10760256 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature