Clonal haematopoiesis of indeterminate potential and mortality in coronary artery disease.

Background And Aims: Clonal haematopoiesis of indeterminate potential (CHIP) has been associated with cardiovascular risk, but its prognostic relevance and mechanistic role in coronary artery disease (CAD) remains incompletely understood. This study investigated the association between CHIP and all-cause mortality in CAD and explored the cellular and molecular mechanisms, focusing on TET2 mutations.

Methods: Targeted deep sequencing of 13 CHIP driver genes in 8612 patients with angiographically confirmed CAD was performed.

Closing the loop: Teaching single-cell foundation models to learn from perturbations.

The application of transfer learning models to large scale single-cell datasets has enabled the development of single-cell foundation models (scFMs) that can predict cellular responses to perturbations in silico. Although these predictions can be experimentally tested, current scFMs are unable to "close the loop" and learn from these experiments to create better predictions. Here, we introduce a "closed-loop" framework that extends the scFM by incorporating perturbation data during model fine-tuning.

Incident cytopenia and risk of subsequent myeloid neoplasm in age-related clonal hematopoiesis: a multi-biobank case-control study.

Background: Cross sectional studies have demonstrated patients with clonal hematopoiesis of indeterminate potential (CHIP) are at increased risk of developing multiple adverse outcomes, including cytopenia and myeloid neoplasm (MN). One prior study suggests cytopenia or cytosis is a required intermediate step in disease progression from CHIP to MN.

Methods: We analyzed genomic sequencing data from the NIH All of Us Research Program, Vanderbilt's BioVU repository, and UK Biobank participants (N = 805,249).

Bone Marrow Niche in Cardiometabolic Disease: Mechanisms and Therapeutic Potential.

Cardiovascular and cardiometabolic diseases are leading causes of morbidity and mortality worldwide, driven in part by chronic inflammation. Emerging research suggests that the bone marrow microenvironment, or marrow niche, plays a critical role in both immune system regulation and disease progression. The bone marrow niche is essential for maintaining hematopoietic stem cells (HSCs) and orchestrating hematopoiesis.

A blueprint for pursuing therapeutic interventions and early phase clinical trials in clonal haematopoiesis.

The age-associated mutational state of clonal haematopoiesis (CH) is linked to multiple adverse health outcomes. As higher risk CH can lead to progressive neoplastic or vascular disease, there is interest in developing clinical trials to mitigate risk associated with CH. Given the high prevalence of CH, data from clinical trials could have broad public health implications for screening and therapy.