ArticleGenome research2014
Improved exome prioritization of disease genes through cross-species phenotype comparison.
Article in Genome research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 229 papers, 1 of them a synthesis that pooled it.
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Who cites it
229 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Computational resources associating diseases with genotypes, phenotypes and exposures.Briefings in bioinformatics · 2019Pooled it
- Use of whole genome sequencing to determine genetic basis of suspected mitochondrial disorders: cohort study.BMJ (Clinical research ed.) · 2021Trial
- Evaluation of Presumably Disease Causing SCN1A Variants in a Cohort of Common Epilepsy Syndromes.PloS one · 2016Trial
- Artificial Intelligence in Neuromuscular Diseases: Opportunities for a Data-Scarce Field.Neurology and therapy · 2026Review
- Translating transcriptomics analysis into diagnostic workflows: clinical variant identification and interpretation in hypothesis-driven and hypothesis-free approaches.EBioMedicine · 2026Article
- INDIGENA: inductive prediction of disease-gene associations using phenotype ontologies.Bioinformatics (Oxford, England) · 2026Article
- A global survey of systems biology-based predictions of gene-rare disease associations to enhance new diagnoses.Scientific reports · 2026Article
- Data-driven prioritization of mouse strains for improved preclinical modeling of rare and common disease.bioRxiv : the preprint server for biology · 2026Article
- Biallelic PAX7 variants cause a novel Satellite Cell-opathy with progressive muscle involvement resembling facioscapulohumeral muscular dystrophy.Cell death & disease · 2026Article
- Harnessing artificial intelligence for genomic variant prediction: advances, challenges, and future directions.GigaScience · 2026Review
- A Phenotypic Paradigm for Cerebral Palsy Genetics.medRxiv : the preprint server for health sciences · 2026Article
- AFrontiers in immunology · 2026Article
- Compound inheritance of EHHADH and MASP1 mutations contributes to nonsyndromic cleft lip: familial analysis and zebrafish models.Biology open · 2025Article
- Comparison of missing data handling methods for variant pathogenicity predictors.NAR genomics and bioinformatics · 2025Article
- Congenital Anomalies in a Neonate With Partial Monosomy of Chromosome 21 q Arm: A Case Report.Cureus · 2025Article
- Accelerate the discovery of genetic variants in mitochondrial diseases with Variant prIOritization using Latent spAce.Briefings in bioinformatics · 2025Article
- An optimized variant prioritization process for rare disease diagnostics: recommendations for Exomiser and Genomiser.Genome medicine · 2025Article
- Exclusion-based exome sequencing in critically ill adults 18-40 years old has a 24% diagnostic rate and finds racial disparities in access to genetic testing.American journal of human genetics · 2025Article
- Identification of technically challenging variants: Whole-genome sequencing improves diagnostic yield in patients with high clinical suspicion of rare diseases.HGG advances · 2025Article
- Few shot learning for phenotype-driven diagnosis of patients with rare genetic diseases.NPJ digital medicine · 2025Article
169 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
Numerous new disease-gene associations have been identified by whole-exome sequencing studies in the last few years. However, many cases remain unsolved due to the sheer number of candidate variants remaining after common filtering strategies such as removing low quality and common variants and those deemed unlikely to be pathogenic. The observation that each of our genomes contains about 100 genuine loss-of-function variants makes identification of the causative mutation problematic when using these strategies alone. We propose using the wealth of genotype to phenotype data that already exists from model organism studies to assess the potential impact of these exome variants. Here, we introduce PHenotypic Interpretation of Variants in Exomes (PHIVE), an algorithm that integrates the calculation of phenotype similarity between human diseases and genetically modified mouse models with evaluation of the variants according to allele frequency, pathogenicity, and mode of inheritance approaches in our Exomiser tool. Large-scale validation of PHIVE analysis using 100,000 exomes containing known mutations demonstrated a substantial improvement (up to 54.1-fold) over purely variant-based (frequency and pathogenicity) methods with the correct gene recalled as the top hit in up to 83% of samples, corresponding to an area under the ROC curve of >95%. We conclude that incorporation of phenotype data can play a vital role in translational bioinformatics and propose that exome sequencing projects should systematically capture clinical phenotypes to take advantage of the strategy presented here.
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