ArticleScientific reports2017
Common sequence variants affect molecular function more than rare variants?
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Predicting Functional Effects of Synonymous Variants: A Systematic Review and Perspectives.Frontiers in genetics · 2019Pooled it
- Expert-guided protein language models enable accurate and blazingly fast fitness prediction.Bioinformatics (Oxford, England) · 2024Article
- Variant Effect Prediction in the Age of Machine Learning.Cold Spring Harbor perspectives in biology · 2024Review
- Protein embeddings and deep learning predict binding residues for various ligand classes.Scientific reports · 2021Article
- Pathogenic missense protein variants affect different functional pathways and proteomic features than healthy population variants.PLoS biology · 2021Article
- Low Diversity of Human Variation Despite Mostly Mild Functional Impact of De Novo Variants.Frontiers in molecular biosciences · 2021Article
- Structure analysis of deleterious nsSNPs in human PALB2 protein for functional inference.Bioinformation · 2021Article
- Protein-protein and protein-nucleic acid binding residues important for common and rare sequence variants in human.BMC bioinformatics · 2020Article
- Protein-Protein Interactions Mediated by Intrinsically Disordered Protein Regions Are Enriched in Missense Mutations.Biomolecules · 2020Article
- Variant effect predictions capture some aspects of deep mutational scanning experiments.BMC bioinformatics · 2020Article
- Assessment of methods for predicting the effects of PTEN and TPMT protein variants.Human mutation · 2019Article
- On estimating evolutionary probabilities of population variants.BMC evolutionary biology · 2019Article
- The variome concept: focus on CNVariome.Molecular cytogenetics · 2019Article
- Linking Clinical Parameters and Genotype in Dilated Cardiomyopathy.Circulation. Heart failure · 2018Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
Any two unrelated individuals differ by about 10,000 single amino acid variants (SAVs). Do these impact molecular function? Experimental answers cannot answer comprehensively, while state-of-the-art prediction methods can. We predicted the functional impacts of SAVs within human and for variants between human and other species. Several surprising results stood out. Firstly, four methods (CADD, PolyPhen-2, SIFT, and SNAP2) agreed within 10 percentage points on the percentage of rare SAVs predicted with effect. However, they differed substantially for the common SAVs: SNAP2 predicted, on average, more effect for common than for rare SAVs. Given the large ExAC data sets sampling 60,706 individuals, the differences were extremely significant (p-value < 2.2e-16). We provided evidence that SNAP2 might be closer to reality for common SAVs than the other methods, due to its different focus in development. Secondly, we predicted significantly higher fractions of SAVs with effect between healthy individuals than between species; the difference increased for more distantly related species. The same trends were maintained for subsets of only housekeeping proteins and when moving from exomes of 1,000 to 60,000 individuals. SAVs frozen at speciation might maintain protein function, while many variants within a species might bring about crucial changes, for better or worse.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.