Crofts, S. | Search bioRxiv

bioRxiv2025

Inference of clonal hematopoiesis using the collective behaviour of DNA methylation states

Clonal expansion occurs when descendants of a single progenitor cell come to dominate a tissue. We show that this process generates a predictable collective behaviour in DNA methylation landscapes: at CpG sites that faithfully transmit their allelic methylation status across cell divisions, methylation proportions shift toward discrete values (0%, 50%, or 100%) as clones expand. We demonstrate this phenomenon in clonal hematopoiesis, in which a hematopoietic stem cell acquires a fitness-conferring mutation that leads to clonal expansion. Exploiting these dynamics, we developed COMET (Clonal Observation from METhylation), which quantifies clonal burden from bulk methylation data without prior knowledge of driving mutations. Validation against targeted sequencing demonstrated robust prediction across mutation types, accurate longitudinal tracking, and detection of sequencing artifacts. Applied to 15,900 individuals, COMET-predicted clonal hematopoiesis replicated known genetic associations (TCL1A, NRIP1) and phenotypic relationships with smoking and chronic obstructive pulmonary disease. These findings reveal fundamental principles of how clonal dynamics manifest epigenetically and establish a mutation-agnostic approach for clonal burden assessment.

genetics↗

bioRxiv2024

Something to sink your teeth into: the mechanics of tooth indentation in frugivorous fishes

Frugivorous vertebrates engage in a mutualism with fruiting plants: the former receive a nutrient subsidy and the latter benefit by having their seeds distributed far from parent plants. Vertebrate frugivores like primates and bats have particular morphologies, like wide jaws and blunt teeth, which are thought to aid in dismantling fruit and obtaining trapped sugars. However, variation among frugivores and fruits has made the identification of common frugivore phenotypes difficult. We measured the performance of frugivorous fish dentitions whether this performance was comparable to fruit-eating bats and primates. We also explored how fruit characteristics affect puncture performance, and how indentation of fruit differs mechanically from harder foods like nuts. Finally, we used photoelasticity and videography to visualize how serrasalmid dentitions propagate stresses in simple gel models. We expected that frugivore dentitions would exhibit low force and then high work when engaging fruit tissues. Aligning with our expectation, the most frugivorous serrasalmid we tested, Colossoma, had dental performance that matched the low force, high work model. Indentation behavior differed between food types, both between fruits and nuts, and among different fruits. We also documented considerable differences in the indentation performances of different serrasalmid dentitions, among frugivores, omnivores, and carnivores. We propose that some differences in the morphology of frugivore dentitions make them better for granivory (eating seeds) than the softer fruit tissues. Fishes exhibit convergent mechanical and morphological strategies with other vertebrates for obtaining nutrition from fruits and seeds.

evolutionary biology↗