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GLOF: A large-scale expert-curated benchmark dataset of gain-of-function and loss-of-function missense variants

Distinguishing loss-of-function (LOF) from gain-of-function (GOF) effects of missense variants is fundamental to understanding disease mechanisms and guiding therapeutic strategy, yet no large-scale, expert-curated benchmark has been publicly available for this task. Here we present GLOF (Gain and Loss Of Function), a dataset of 112,399 missense variants across 2,809 human genes, each classified as LOF, GOF, or neutral by board-certified clinical geneticists following ACMG guidelines....

bioRxiv 3d ago

ZX-Calculus:Trace-Indexed Dependent Types and Epistemic Semantics

Announce Type: new Abstract: We propose ZX-Calculus (Knowledge Evolution Calculus), a conservative extension of Martin-Lof Dependent Type Theory (MLTT) integrating trace-indexed types, presheaf non-monotone semantics, and constructive AGM belief revision. A Coq mechanisation accompanies the paper (34 complete proofs; zero admits for the two central results). FinTrace(s0,sn) is an inductive family of typed execution traces.

arXiv CS 7d ago

Mutation-dependent responses to sleep and exercise in clonal haematopoiesis

Abstract Clonal haematopoiesis (CH) activates inflammation and increases the risk of atherosclerosis1,2. Whether lifestyle alters CH clone expansion or the phenotypic programming of CH mutant cells, thereby affecting atherosclerosis, is unknown. Here, in humans and mice and across mutations in Jak2, Tet2, Trp53 and Dnmt3a, we demonstrate mutation-dependent responses to sleep and exercise in CH and show that mutant cells are uniquely sensitive to lifestyle.

Nature 19h ago