ArticleBioinformatics (Oxford, England)2009
Identifying novel constrained elements by exploiting biased substitution patterns.
Article in Bioinformatics (Oxford, England), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 231 papers, 9 of them syntheses that pooled it.
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Who cites it
231 citing papers in PubMed, 9 syntheses or guidelines pooled it.
- Large-Scale Genome-Wide Association Study of East Asians Identifies Loci Associated With Risk for Colorectal Cancer.Gastroenterology · 2019Pooled it
- Large-scale genome-wide meta-analysis of polycystic ovary syndrome suggests shared genetic architecture for different diagnosis criteria.PLoS genetics · 2018Pooled it
- Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants.Nature communications · 2018Pooled it
- New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475 000 Individuals.Circulation. Cardiovascular genetics · 2017Pooled it
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- HLA class II sequence variants influence tuberculosis risk in populations of European ancestry.Nature genetics · 2016Pooled it
- Meta-analysis of genome-wide association studies identifies multiple lung cancer susceptibility loci in never-smoking Asian women.Human molecular genetics · 2016Pooled it
- Fine mapping of the celiac disease-associated LPP locus reveals a potential functional variant.Human molecular genetics · 2014Pooled it
- Next-generation sequencing-based molecular diagnosis of 82 retinitis pigmentosa probands from Northern Ireland.Human genetics · 2015Trial
- From conservation scores to language models: a feature engineering perspective on machine learning for genetic variant interpretation.Briefings in bioinformatics · 2026Review
- Expanding the ocular and genetic spectrum of FLVCR1-associated disease in a Chinese cohort.Documenta ophthalmologica. Advances in ophthalmology · 2026Article
- DeNovoSeer:a deep learning framework for pathogenicity prediction of De novo mutations.Briefings in bioinformatics · 2026Article
- Pervasive cryptic selection in the human noncoding genome.bioRxiv : the preprint server for biology · 2026Article
- MENDELSEEK: An algorithm that predicts mendelian genes and elucidates what makes them special.PLoS computational biology · 2026Article
- The Performance ofHuman mutation · 2026Article
- MutAnt: mutation annotation tool predicts deleteriousness of missense mutations and improves mutation calling from transcriptomics.Human genetics · 2025Article
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- Evaluating variant pathogenicity prediction tools to establish African inclusive guidelines for germline genetic testing.Communications medicine · 2025Article
- A series of reviews in familial cancer: genetic cancer risk in context variants of uncertain significance in MMR genes: which procedures should be followed?Familial cancer · 2025Review
171 more citing papers are in PubMed but not listed here.
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6 authors.
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No grant is acknowledged in the PubMed record.
Abstract
motivationComparing the genomes from closely related species provides a powerful tool to identify functional elements in a reference genome. Many methods have been developed to identify conserved sequences across species; however, existing methods only model conservation as a decrease in the rate of mutation and have ignored selection acting on the pattern of mutations.
resultsWe present a new approach that takes advantage of deeply sequenced clades to identify evolutionary selection by uncovering not only signatures of rate-based conservation but also substitution patterns characteristic of sequence undergoing natural selection. We describe a new statistical method for modeling biased nucleotide substitutions, a learning algorithm for inferring site-specific substitution biases directly from sequence alignments and a hidden Markov model for detecting constrained elements characterized by biased substitutions. We show that the new approach can identify significantly more degenerate constrained sequences than rate-based methods. Applying it to the ENCODE regions, we identify as much as 10.2% of these regions are under selection. AVAILABILITY: The algorithms are implemented in a Java software package, called SiPhy, freely available at http://www.broadinstitute.org/science/software/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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