Our framework enables more accurate prediction of CH's clinical impact, moving us closer to personalized risk assessment and potential intervention strategies.

MACS120 outperformed traditional measurements (like variant allele frequency) in predicting mortality risk and showed increased correlations with the speed of change in blood markers like lymphocyte and albumin levels.

Considering these factors, we developed MACS120 - a novel metric that combines mutation fitness and acquisition timing to predict maximum clone size a mutation will reach over a lifetime.

Third, we discovered a strong correlation between mutation timing, or age at time of mutation acquisition (ATMA), and fitness. Higher fitness mutations tend to appear later in life - possibly due to declining quality control mechanisms with age.

Similarly, mutations can have different fitness effects depending on what other mutations are present in the same clone. For example, ASXL1 mutations have higher fitness when co-occurring with SRSF2 than with TET2.

Second, we found that clonal coexistence matters! Mutations don't grow in isolation - when multiple clones are present in the same person, they alter each other's overall contribution to the production of blood cells.

First, we confirmed gene-specific fitness differences: RNA splicing mutations (like U2AF1, U2AF2) show higher fitness than epigenetic regulator mutations (like DNMT3A, TET2).

Our key insight: Three factors, mutation fitness (growth advantage), mutation timing, and clonal structure (which mutations occur together) are needed to understand the progression and clinical impact of CH.

We integrated data from 713 individuals across 3 longitudinal aging cohorts (2,341 observations total) and developed models to understand the dynamics of CH mutations over time. #CancerResearch #ClonalHematopoiesis

Clonal hematopoiesis (CH) is common in aging populations and associated with increased risk of blood cancers and other diseases. But what determines which CH mutations will progress to disease?

Excited to be part of this amazing workshop. Thanks for organising @megvoda.bsky.social

Pleasure to host you as always!

Congratulations on this nice piece of work!