Proteome-wide prediction and structural modeling of disordered protein interaction interfaces advance characterization of disease-associated variants in disordered protein regions.

AlphaFold’s success in protein structure predictions has led to similar attempts to predict interactomes. Here, the authors demonstrate that AI-based screens are very limited in discovering truly nove...

Recessive diseases arise from the combined effects of two alleles, yet most variant interpretation methods consider variants individually. Çubuk et al. map more than 8,000 variants in the recessive en...

Nature Microbiology, Published online: 26 January 2026; doi:10.1038/s41564-025-02241-yLarge-scale computational and in vitro analyses identify commensal type III secretion systems and substrates in the human gut microbiome that can interact with human proteins to modulate immune pathways.

Large-scale computational and in vitro analyses identify commensal type III secretion systems and substrates in the human gut microbiome that can interact with human proteins to modulate immune pathwa...

Generative biology holds the promise to transform our ability to design and understand living systems by creating novel proteins, pathways, and organisms with tailored functions that address challenge...

Variant effect prediction remains a key challenge to resolve in precision medicine. Sophisticated computational models that exploit sequence conservation and structure are increasingly successful in t...

Reverse electron transport is the mechanism behind excess mitochondrial reactive oxygen species in the livers of obese mice, which has implications for developing therapeutics for fatty liver dis...

Lambourne, Mattioli, Santoso, et al. compare protein isoforms of the same transcription factor genes through high-throughput profiling of DNA-binding, protein-binding, activation, localization, and condensate formation. Differences between isoforms are widespread, often unpredictable from sequence differences, and inform a disease-associated categorization of alternative isoforms into rewirers or negative regulators.

Lambourne, Mattioli, Santoso, et al. compare protein isoforms of the same transcription factor genes through high-throughput profiling of DNA-binding, protein-binding, activation, localization, and condensate formation. Differences between isoforms are widespread, often unpredictable from sequence differences, and inform a disease-associated categorization of alternative isoforms into rewirers or negative regulators.

Reduced protein stability is the most frequent mechanism by which rare missense variants cause disease. A promising therapeutic avenue for treating destabilizing variants is pharmacological chaperones...