Scalable functional assays for the interpretation of human genetic variation

D Tabet, V Parikh, P Mali, FP Roth… - Annual Review of …, 2022 - annualreviews.org
Scalable sequence–function studies have enabled the systematic analysis and cataloging of
hundreds of thousands of coding and noncoding genetic variants in the human genome …

Humanized yeast to model human biology, disease and evolution

AH Kachroo, M Vandeloo, BM Greco… - Disease models & …, 2022 - journals.biologists.com
For decades, budding yeast, a single-cellular eukaryote, has provided remarkable insights
into human biology. Yeast and humans share several thousand genes despite …

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 …

Proteingym: Large-scale benchmarks for protein fitness prediction and design

P Notin, A Kollasch, D Ritter… - Advances in …, 2024 - proceedings.neurips.cc
Predicting the effects of mutations in proteins is critical to many applications, from
understanding genetic disease to designing novel proteins to address our most pressing …

Saturation variant interpretation using CRISPR prime editing

S Erwood, TMI Bily, J Lequyer, J Yan, N Gulati… - Nature …, 2022 - nature.com
High-throughput functional characterization of genetic variants in their endogenous locus
has so far been possible only with methods that rely on homology-directed repair, which are …

Updated benchmarking of variant effect predictors using deep mutational scanning

BJ Livesey, JA Marsh - Molecular systems biology, 2023 - embopress.org
The assessment of variant effect predictor (VEP) performance is fraught with biases
introduced by benchmarking against clinical observations. In this study, building on our …

[HTML][HTML] Improved pathogenicity prediction for rare human missense variants

Y Wu, H Liu, R Li, S Sun, J Weile, FP Roth - The American Journal of …, 2021 - cell.com
The success of personalized genomic medicine depends on our ability to assess the
pathogenicity of rare human variants, including the important class of missense variation …

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

MH Høie, M Cagiada, AHB Frederiksen, A Stein… - Cell reports, 2022 - cell.com
Understanding and predicting the functional consequences of single amino acid changes is
central in many areas of protein science. Here, we collect and analyze experimental …

Discovering functionally important sites in proteins

M Cagiada, S Bottaro, S Lindemose… - Nature …, 2023 - nature.com
Proteins play important roles in biology, biotechnology and pharmacology, and missense
variants are a common cause of disease. Discovering functionally important sites in proteins …

Massively parallel functional testing of MSH2 missense variants conferring Lynch syndrome risk

X Jia, BB Burugula, V Chen, RM Lemons… - The American Journal of …, 2021 - cell.com
The lack of functional evidence for the majority of missense variants limits their clinical
interpretability and poses a key barrier to the broad utility of carrier screening. In Lynch …