A. Stein

Systematic characterization of indel variants using a yeast-based protein folding sensor

The paper develops a yeast-based protein folding sensor to study indel variants, finding that most tolerated indels occur in specific regions and that computational tools can predict their effects.

Selective sweep probabilities in spatially expanding populations

The paper calculates selective sweep probabilities in spatially expanding populations and finds they depend on mutant and wildtype expansion speeds and spatial dimension, with implications for tumour evolution.

A mutational atlas for Parkin proteostasis

This study maps Parkin missense variants' abundance and degradation mechanisms, showing most low-abundance variants are degraded via the ubiquitin-proteasome system and stabilized at lower temperatures.

Characterizing glucokinase variant mechanisms using a multiplexed abundance assay

The paper characterizes mechanisms of human glucokinase variants by analyzing their abundance and stability, identifying residues that affect metabolic stability and conformational dynamics.

Rare catechol-O-methyltransferase (COMT) missense variants are structurally unstable proteasome targets

The paper shows two rare COMT missense variants are structurally unstable, leading to proteasomal degradation and reduced enzyme levels, with degradation independent of COMT isoform.

Rapid protein stability prediction using deep learning representations

This paper introduces RaSP, a deep learning method for rapid protein stability prediction, showing it matches biophysics-based methods and reveals population-level patterns in stability changes.

Discovering functionally important sites in proteins

This paper introduces a machine learning method to predict functional sites in proteins by integrating sequence conservation and biophysical stability models, validated through experimental data on missense variants.

Accurate protein stability predictions from homology models

This study evaluates the accuracy of protein stability predictions from homology models compared to crystal structures, finding they perform equally well when sequence identity is at least 40%.

Interpreting the molecular mechanisms of disease variants in human membrane proteins

This paper investigates missense variants in human membrane proteins, finding that loss of stability is a common mechanism for pathogenicity in over half of the studied variants.

Machine learning improves global models of plant diversity

The paper uses machine learning and statistical models to predict global plant diversity patterns based on environmental data, achieving high accuracy for species and phylogenetic richness.

HSP70-binding motifs function as protein quality control degrons

The paper shows that Hsp70-binding motifs can function as PQC degrons, targeting misfolded proteins for degradation in yeast and human cells.

Disease-linked mutations trigger exposure of a protein quality control degron in the DHFR protein

The paper identifies two PQC degrons in DHFR that become exposed in disease-linked missense variants, leading to proteasomal degradation.

A structural biology community assessment of AlphaFold 2 applications

This study assesses AlphaFold 2's applications in structural biology, finding it outperforms existing tools in predicting disorder, complexes, and structural features with high confidence.

Predicting and interpreting large scale mutagenesis data using analyses of protein stability and conservation

The paper predicts and interprets large-scale mutagenesis data by analyzing protein stability and conservation, finding that sequence conservation provides more accurate variant effect predictions than stability calculations.

Mapping Twenty Years of Antimicrobial Resistance Research Trends

This study uses topic modelling to analyze 158,616 AMR research articles from 1999-2018, revealing key topics, trends, and geographical patterns in the field.

Understanding the origins of loss of protein function by analyzing the effects of thousands of variants on activity and abundance

The paper analyzes variant effects on protein activity and abundance in NUDT15 and PTEN, finding that a third of variants cause loss of function and half of these also reduce abundance.

Evolutionarily conserved chaperone-mediated proteasomal degradation of a disease-linked aspartoacylase variant

This study investigates the degradation pathway of a disease-linked ASPA variant, finding it is degraded via the proteasome and dependent on Hsp70 and Hsp110.

Computational and cellular studies reveal structural destabilization and degradation of MLH1 variants in Lynch syndrome

The paper identifies structural destabilization and degradation of MLH1 variants in Lynch syndrome, linking reduced cellular levels to loss-of-function and suggesting stability predictions for diagnostic use.

Classifying disease-associated variants using measures of protein activity and stability

The paper classifies PTEN missense variants as pathogenic or benign using experimental and computational methods, finding that ~60% of pathogenic variants destabilize the protein.

Disharmony of the world’s island floras

The paper quantitatively assesses island disharmony by analyzing 320 island floras and 450 plant families, finding compositional bias linked to island characteristics rather than family traits.