Novel machine learning approaches revolutionize protein knowledge

N Bordin, C Dallago, M Heinzinger, S Kim… - Trends in Biochemical …, 2023 - cell.com
Breakthrough methods in machine learning (ML), protein structure prediction, and novel
ultrafast structural aligners are revolutionizing structural biology. Obtaining accurate models …

Accurate proteome-wide missense variant effect prediction with AlphaMissense

J Cheng, G Novati, J Pan, C Bycroft, A Žemgulytė… - Science, 2023 - science.org
The vast majority of missense variants observed in the human genome are of unknown
clinical significance. We present AlphaMissense, an adaptation of AlphaFold fine-tuned on …

Conformational ensembles of the human intrinsically disordered proteome

G Tesei, AI Trolle, N Jonsson, J Betz, FE Knudsen… - Nature, 2024 - nature.com
Intrinsically disordered proteins and regions (collectively, IDRs) are pervasive across
proteomes in all kingdoms of life, help to shape biological functions and are involved in …

CADD v1. 7: using protein language models, regulatory CNNs and other nucleotide-level scores to improve genome-wide variant predictions

M Schubach, T Maass, L Nazaretyan… - Nucleic acids …, 2024 - academic.oup.com
Abstract Machine Learning-based scoring and classification of genetic variants aids the
assessment of clinical findings and is employed to prioritize variants in diverse genetic …

The power of computational proteomics platforms to decipher protein-protein interactions

M González-Avendaño, J López… - Current Opinion in …, 2024 - Elsevier
Adopting computational tools for analyzing extensive biological datasets has profoundly
transformed our understanding and interpretation of biological phenomena. Innovative …

Cross-protein transfer learning substantially improves disease variant prediction

M Jagota, C Ye, C Albors, R Rastogi, A Koehl… - Genome Biology, 2023 - Springer
Background Genetic variation in the human genome is a major determinant of individual
disease risk, but the vast majority of missense variants have unknown etiological effects …

Conformational ensembles of the human intrinsically disordered proteome: Bridging chain compaction with function and sequence conservation

G Tesei, AI Trolle, N Jonsson, J Betz, F Pesce… - bioRxiv, 2023 - biorxiv.org
Intrinsically disordered proteins and regions (collectively IDRs) are pervasive across
proteomes in all kingdoms of life, help shape biological functions, and are involved in …

Accurate prediction by AlphaFold2 for ligand binding in a reductive dehalogenase and implications for PFAS (per-and polyfluoroalkyl substance) biodegradation

HB Guo, VA Varaljay, G Kedziora, K Taylor… - Scientific Reports, 2023 - nature.com
Despite the success of AlphaFold2 (AF2), it is unclear how AF2 models accommodate for
ligand binding. Here, we start with a protein sequence from Acidimicrobiaceae TMED77 …

Evaluating the use of paralogous protein domains to increase data availability for missense variant classification

AC Gunning, CF Wright - Genome Medicine, 2023 - Springer
Background Classification of rare missense variants remains an ongoing challenge in
genomic medicine. Evidence of pathogenicity is often sparse, and decisions about how to …

Toward physics‐based precision medicine: Exploiting protein dynamics to design new therapeutics and interpret variants

A Meller, D Kelly, LG Smith, GR Bowman - Protein Science, 2024 - Wiley Online Library
The goal of precision medicine is to utilize our knowledge of the molecular causes of
disease to better diagnose and treat patients. However, there is a substantial mismatch …