How low can you go?: Methodologic considerations in clonal hematopoiesis variant calling

Clonal hematopoiesis (CH) is defined by the presence of an expanded clonal hematopoietic cell population due to an acquired mutation conferring a selective growth advantage and is known to predispose to hematologic malignancy. In this review, we discuss sequencing methods for CH detection in bulk sequencing data and corresponding bioinformatic approaches for variant calling, filtering, and curation. We detail practical recommendations for CH calling. Finally, we discuss how improvements in CH sequencing and bioinformatic approaches will enable the characterization of CH trajectories, its impact on human health, and therapeutic approaches to mitigate its adverse effects.