CAGI, the Critical Assessment of Genome Interpretation, establishes progress and prospects for computational genetic variant interpretation methods

• Background: The Critical Assessment of Genome Interpretation (CAGI) aims to advance the state-of-the-art for computational prediction of genetic variant impact, particularly where relevant to disease. The five complete editions of the CAGI community experiment comprised 50 challenges, in which participants made blind predictions of phenotypes from genetic data, and these were evaluated by independent assessors. Results: Performance was particularly strong for clinical pathogenic variants, including some difficult-to-diagnose cases, and extends to interpretation of cancer-related variants. Missense variant interpretation methods were able to estimate biochemical effects with increasing accuracy. Assessment of methods for regulatory variants and complex trait disease risk was less definitive and indicates performance potentially suitable for auxiliary use in the clinic. Conclusions: Results show that while current methods are imperfect, they have major utility for research and clinical applications. Emerging methods and increasingly large, robust datasets for training and assessment promise further progress ahead. © The Author(s) 2024.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)

Nyckelord

nucleotide

area under the curve

art

Article

biochemistry

cancer risk

CDKN2A gene

cell growth

CHEK2 gene

clinical practice

complex trait disease risk

computational genetic variant interpretation method

computer model

correlation coefficient

Critical Assessment of Genome Interpretation

Crohn disease

diagnostic accuracy

diagnostic test accuracy study

diseases

DNA repair

DNA splicing

effect size

environmental risk

enzyme activity

FXN gene

gene deletion

gene expression

gene insertion

gene linkage disequilibrium

genetic analysis

genetic database

genetic identification

genetic information

genetic trait

genetic transcription

genetic variability

genetic variation

genome

genome-wide association study

genomic scale

germline mutation

human

intellectual impairment

interpretation bias

malignant neoplasm

medical research

missense mutation

monogenic disorder

MRE11 gene

multiomics

NBS1 gene

NPMALK gene

NSMCE2 gene

pathogenicity

phenotype

practice guideline

prediction

protein function

protein stability

PTEN gene

RAD50 gene

receiver operating characteristic

regulatory mechanism

social aspect

structure analysis

TP53 gene

TPMT gene

tumor suppressor gene

whole organism fitness

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art (ämneskategori)

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