☆ 4.6 Article

Updated benchmarking of variant effect predictors using deep mutational scanning

MOLECULAR SYSTEMS BIOLOGY (2023)

相关参考文献

注意：仅列出部分参考文献，下载原文获取全部文献信息。

Article Genetics & Heredity

Embeddings from protein language models predict conservation and variant effects

Celine Marquet et al.

Summary: The study utilized Protein Language Models (pLMs) to predict sequence conservation and SAV effects without requiring multiple sequence alignments (MSAs). The results showed that embeddings alone could accurately predict residue conservation almost as effectively as ConSeq using MSAs.

HUMAN GENETICS (2022)

添加到收藏夹

Review Cell Biology

Interpreting protein variant effects with computational predictors and deep mutational scanning

Benjamin J. Livesey et al.

Summary: Computational predictors of genetic variant effect have made significant advancements, providing a rapid and scalable method to assess the impacts of new variants. However, the trustworthiness of their results may be uncertain. Benchmarking against large datasets of known variants is common, but overlapping with training data can lead to inflated performance estimates. Deep mutational scans offer an independent solution to this issue.

DISEASE MODELS & MECHANISMS (2022)

添加到收藏夹

Article Clinical Neurology

α-Synuclein V15A Variant in Familial Parkinson's Disease Exhibits a Weaker Lipid-Binding Property

Kensuke Daida et al.

Summary: The V15A variant of α-Synuclein (α-Syn) may be associated with the development of Parkinson's disease (PD). This variant has reduced affinity for phospholipids and increased propagation activity compared to the wild-type.

MOVEMENT DISORDERS (2022)

添加到收藏夹

Article Multidisciplinary Sciences

Loss-of-function, gain-of-function and dominant-negative mutations have profoundly different effects on protein structure

Lukas Gerasimavicius et al.

Summary: The study investigates the effects of pathogenic missense mutations on protein structure, showing that dominant non-loss-of-function mutations have milder impact on protein structure, and dominant-negative mutations are enriched at protein interfaces. It also finds that computational variant effect predictors perform poorly on non-loss-of-function mutations, but clustering in three-dimensional space could potentially identify these mutations.

NATURE COMMUNICATIONS (2022)

添加到收藏夹

Article Genetics & Heredity

Assessing performance of pathogenicity predictors using clinically relevant variant datasets

Adam C. Gunning et al.

Summary: This study validated the performance of several new meta-predictors in a clinically relevant dataset, and found that while the new meta-predictors outperformed traditional tools, all pathogenicity predictors showed lower performance in the clinically relevant dataset, with REVEL performing the best.

JOURNAL OF MEDICAL GENETICS (2021)

添加到收藏夹

Article Genetics & Heredity

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

Xiaoyan Jia et al.

Summary: The majority of missense variants in Lynch syndrome were found to be functionally neutral despite evolutionary conservation. A functional effect map of MSH2 missense variants was developed through a large-scale parallel screen, which may help resolve existing and newly discovered variants for classification in the clinic.

AMERICAN JOURNAL OF HUMAN GENETICS (2021)

添加到收藏夹

Article Multidisciplinary Sciences

Disease variant prediction with deep generative models of evolutionary data

Jonathan Frazer et al.

Summary: Quantifying the pathogenicity of protein variants in human disease-related genes is important for clinical decisions, but most variants still have unknown consequences. Current computational methods rely on training machine learning models on known disease labels, resulting in unreliable models due to sparse and biased labels.

NATURE (2021)

添加到收藏夹

Article Genetics & Heredity

Improved pathogenicity prediction for rare human missense variants

Yingzhou Wu et al.

Summary: The study introduces a new method called VARITY, which uses a larger training example pool to improve the accuracy of computational systems in assessing pathogenicity of rare human variants, and excludes features informed by variant annotation and protein identity to reduce bias. VARITY outperformed previous computational methods in identifying pathogenic variants.

AMERICAN JOURNAL OF HUMAN GENETICS (2021)

添加到收藏夹

Article Genetics & Heredity

Shifting landscapes of human MTHFR missense-variant effects

Jochen Weile et al.

Summary: Most rare clinical missense variants, including the MTHFR variant impact, cannot be easily classified, as variant effects in MTHFR deficiency depend on environmental factors. The MTHFR atlas scores can differentiate pathogenic from benign variants and correlate with disease onset age in severe MTHFR deficiency. The atlas provides insights on structure-function relationships and the impact of genetic background on missense variations.

AMERICAN JOURNAL OF HUMAN GENETICS (2021)

添加到收藏夹

Article Genetics & Heredity

Massively parallel characterization of CYP2C9 variant enzyme activity and abundance

Clara J. Amorosi et al.

Summary: The CYP2C9 gene encodes an enzyme that plays a crucial role in metabolizing small molecule drugs, and its variants can impact drug response and increase the risk of bleeding. By utilizing the clickseq and VAMP-seq technologies, researchers measured the activity and cellular abundance of numerous CYP2C9 variants, revealing a significant portion with decreased activity and functional differences attributed to changes in protein abundance.

AMERICAN JOURNAL OF HUMAN GENETICS (2021)

添加到收藏夹

Article Multidisciplinary Sciences

Rare variant contribution to human disease in 281,104 UK Biobank exomes

Quanli Wang et al.

Summary: The study reveals a significant contribution of rare variants to common disease, with a large number of gene-phenotype associations detected through gene-based collapsing analysis that cannot be identified in single-variant association tests. Rare variants are also significantly enriched for loss-of-function-mediated traits and approved drug targets.

NATURE (2021)

添加到收藏夹

Article Clinical Neurology

A new alpha-synuclein missense variant (Thr72Met) in two Turkish families with Parkinson's disease

Christina Fevga et al.

Summary: A novel SNCA variant, c.215C > T (p.Thr72Met), was found to segregate with PD in four members of two Turkish families. Functional analysis showed enhanced aggregation of this variant in vitro, potentially destabilizing the tetramer structure and leading to neurodegeneration. Further studies are needed to explore shared biochemical properties of SNCA missense variants causing PD.

PARKINSONISM & RELATED DISORDERS (2021)

添加到收藏夹

Article Multidisciplinary Sciences

Structure of PDE3A-SLFN12 complex reveals requirements for activation of SLFN12 RNase

Colin W. Garvie et al.

Summary: DNMDP and related compounds induce complex formation between phosphodiesterase PDE3A and SLFN12, leading to cytotoxic response in cancer cells. The formation of a heterotetramer structure stabilized by DNMDP, SLFN12 functioning as an RNase, and the requirement of SLFN12 RNase activity for DNMDP-mediated cancer cell killing were demonstrated. This new mechanistic understanding may facilitate the development of velcrin compounds into novel cancer therapies.

NATURE COMMUNICATIONS (2021)

添加到收藏夹

Article Biochemical Research Methods

Prediction of mutation effects using a deep temporal convolutional network

Ha Young Kim et al.

BIOINFORMATICS (2020)

添加到收藏夹

Article Multidisciplinary Sciences

Massively parallel variant characterization identifies NUDT15 alleles associated with thiopurine toxicity

Chase C. Suiter et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2020)

添加到收藏夹

Article Mathematical & Computational Biology

Variation benchmark datasets: update, criteria, quality and applications

Anasua Sarkar et al.

DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION (2020)

添加到收藏夹

Article Cardiac & Cardiovascular Systems

Deep Mutational Scan of an SCN5A Voltage Sensor

Andrew M. Glazer et al.

CIRCULATION-GENOMIC AND PRECISION MEDICINE (2020)

添加到收藏夹

Article Genetics & Heredity

A proactive genotype-to-patient-phenotype map for cystathionine beta-synthase

Song Sun et al.

GENOME MEDICINE (2020)

添加到收藏夹

Article Multidisciplinary Sciences

The mutational constraint spectrum quantified from variation in 141,456 humans

Konrad J. Karczewski et al.

NATURE (2020)

添加到收藏夹

Article Biochemistry & Molecular Biology

Deep mutational scanning reveals the structural basis for α-synuclein activity

Robert W. Newberry et al.

NATURE CHEMICAL BIOLOGY (2020)

添加到收藏夹

Article Biochemistry & Molecular Biology

LIST-S2: taxonomy based sorting of deleterious missense mutations across species

Nawar Malhis et al.

NUCLEIC ACIDS RESEARCH (2020)

添加到收藏夹

Article Biochemistry & Molecular Biology

Using deep mutational scanning to benchmark variant effect predictors and identify disease mutations

Benjamin J. Livesey et al.

MOLECULAR SYSTEMS BIOLOGY (2020)

添加到收藏夹

Article Clinical Neurology

A novelSNCAE83Q mutation in a case of dementia with Lewy bodies and atypical frontotemporal lobar degeneration

Alifiya Kapasi et al.

NEUROPATHOLOGY (2020)

添加到收藏夹

Article Biology

Multiplexed measurement of variant abundance and activity reveals VKOR topology, active site and human variant impact

Melissa A. Chiasson et al.

ELIFE (2020)

添加到收藏夹

Article Genetics & Heredity

dbNSFP v4: a comprehensive database of transcript-specific functional predictions and annotations for human nonsynonymous and splice-site SNVs

Xiaoming Liu et al.

GENOME MEDICINE (2020)

添加到收藏夹

Article Biochemical Research Methods

How good are pathogenicity predictors in detecting benign variants?

Abhishek Niroula et al.

PLOS COMPUTATIONAL BIOLOGY (2019)

添加到收藏夹

Article Genetics & Heredity

Predicting venous thromboembolism risk from exomes in the Critical Assessment of Genome Interpretation (CAGI) challenges

Gregory McInnes et al.

HUMAN MUTATION (2019)

添加到收藏夹

Article Biotechnology & Applied Microbiology

MaveDB: an open-source platform to distribute and interpret data from multiplexed assays of variant effect

Daniel Esposito et al.

GENOME BIOLOGY (2019)

添加到收藏夹

Article Immunology

Mapping Interaction Sites on Human Chemokine Receptors by Deep Mutational Scanning

Jeremiah D. Heredia et al.

JOURNAL OF IMMUNOLOGY (2018)

添加到收藏夹

Article Biochemistry & Molecular Biology

A Systematic p53 Mutation Library Links Differential Functional Impact to Cancer Mutation Pattern and Evolutionary Conservation

Eran Kotler et al.

MOLECULAR CELL (2018)

添加到收藏夹

Article Genetics & Heredity

Multiplex assessment of protein variant abundance by massively parallel sequencing

Kenneth A. Matreyek et al.

NATURE GENETICS (2018)

添加到收藏夹

Article Biochemistry & Molecular Biology

Quantitative Missense Variant Effect Prediction Using Large-Scale Mutagenesis Data

Vanessa E. Gray et al.

CELL SYSTEMS (2018)

添加到收藏夹

Article Genetics & Heredity

ClinPred: Prediction Tool to Identify Disease-Relevant Nonsynonymous Single-Nucleotide Variants

Najmeh Alirezaie et al.

AMERICAN JOURNAL OF HUMAN GENETICS (2018)

添加到收藏夹

Article Biochemical Research Methods

Deep generative models of genetic variation capture the effects of mutations

Adam J. Riesselman et al.

NATURE METHODS (2018)

添加到收藏夹

Article Pharmacology & Pharmacy

The Pharmacogene Variation (PharmVar) Consortium: Incorporation of the Human Cytochrome P450 (CYP) Allele Nomenclature Database

Andrea Gaedigk et al.

CLINICAL PHARMACOLOGY & THERAPEUTICS (2018)

添加到收藏夹

Article Genetics & Heredity

PERCH: A Unified Framework for Disease Gene Prioritization

Bing-Jian Feng

HUMAN MUTATION (2017)

添加到收藏夹

Article Biotechnology & Applied Microbiology

Mutation effects predicted from sequence co-variation

Thomas A. Hopf et al.

NATURE BIOTECHNOLOGY (2017)

添加到收藏夹

Article Cardiac & Cardiovascular Systems

Elucidating arrhythmogenic mechanisms of long-QT syndrome CALM1-F142L mutation in patient-specific induced pluripotent stem cell-derived cardiomyocytes

Marcella Rocchetti et al.

CARDIOVASCULAR RESEARCH (2017)

添加到收藏夹

Article Genetics & Heredity

REVEL: An Ensemble Method for Predicting the Pathogenicity of Rare Missense Variants

Nilah M. Ioannidis et al.

AMERICAN JOURNAL OF HUMAN GENETICS (2016)

添加到收藏夹

Article Genetics & Heredity

The Evaluation of Tools Used to Predict the Impact of Missense Variants Is Hindered by Two Types of Circularity

Dominik G. Grimm et al.

HUMAN MUTATION (2015)

添加到收藏夹

Article Multidisciplinary Sciences

A global reference for human genetic variation

David M. Altshuler et al.

NATURE (2015)

添加到收藏夹

Article Biochemical Research Methods

UniRef clusters: a comprehensive and scalable alternative for improving sequence similarity searches

Baris E. Suzek et al.

BIOINFORMATICS (2015)

添加到收藏夹

Article Biochemical Research Methods

Deep mutational scanning: a new style of protein science

Douglas M. Fowler et al.

NATURE METHODS (2014)

添加到收藏夹

Article Biochemistry & Molecular Biology

ClinVar: public archive of relationships among sequence variation and human phenotype

Melissa J. Landrum et al.

NUCLEIC ACIDS RESEARCH (2014)

添加到收藏夹

Article Biochemistry & Molecular Biology

Familial mutants of α-synuclein with increased neurotoxicity have a destabilized conformation

CW Bertoncini et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2005)

添加到收藏夹

Article Biochemistry & Molecular Biology

RevTrans: multiple alignment of coding DNA from aligned amino acid sequences

R Wernersson et al.

NUCLEIC ACIDS RESEARCH (2003)

添加到收藏夹

Article Genetics & Heredity

Human gene mutation database (HGMD®):: 2003 update

PD Stenson et al.

HUMAN MUTATION (2003)

添加到收藏夹

© Peeref 2019-2024. All rights reserved.