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...