HaploReg: a resource for exploring chromatin states, conservation, and regulatory motif alterations within sets of genetically linked variants

By Lucas D. Ward, Manolis Kellis. Nucleic Acids Res., 2011

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The resolution of genome-wide association studies (GWAS) is limited by the linkage disequilibrium (LD) structure of the population being studied. Selecting the most likely causal variants within an LD block is relatively straightforward within coding sequence, but is more difficult when all variants are intergenic. Predicting functional non-coding sequence has been recently facilitated by the availability of conservation and epigenomic information. We present HaploReg, a tool for exploring annotations of the non-coding genome among the results of published GWAS or novel sets of variants. Using LD information from the 1000 Genomes Project, linked SNPs and small indels can be visualized along with their predicted chromatin state in nine cell types, conservation across mammals and their effect on regulatory motifs. Sets of SNPs, such as those resulting from GWAS, are analyzed for an enrichment of cell type-specific enhancers. HaploReg will be useful to researchers developing mechanistic hypotheses of the impact of non-coding variants on clinical phenotypes and normal variation. The HaploReg database is available at http://compbio.mit.edu/HaploReg.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/f1efe96bde863cab825b15ee723a5365657172ac

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Citations in the corpus

HaploReg v4: systematic mining of putative causal variants, cell types, regulators and target genes for human complex traits and disease (2015, methodology): “A library of position weight matrices from commercial, literature and motif-finding analysis of the ENCODE project (37) was used to score the effect of variants on regulatory motifs using the position weight matrix (PWM)-scanning process described previously (4).”
FunSeq2: a framework for prioritizing noncoding regulatory variants in cancer (2014, methodology): “A number of tools have been developed using these data to annotate potential regulatory variants or to suggest the most likely causal variants in linkage disequilibrium with GWAS SNPs, such as Haploreg [18], RegulomeDB [19], ANNOVAR [20], GEMINI [21], FunciSNP [22], and VEP [23].”
Systematic Evaluation of Pleiotropy Identifies 6 Further Loci Associated With Coronary Artery Disease (2017, positive): “Interrogation of the 1000 Genomes Project phase 1 EUR data using Haploreg (BROAD Institute, Massachusetts Institute of Technology and Harvard, Boston, Massachusetts) (17) showed that the number of SNPs in high LD (r2 > 0.8) with the lead variant varied between 1 (LRP1 locus and CETP locus) and 111 (”
Systematic discovery and characterization of regulatory motifs in ENCODE TF binding experiments (2013, background): “Because having the motifs allows for more precisely determining the bases responsible for binding, these motifs enable analyzes involving population data (88) and for interpreting GWAS data (89).”
Annotation of functional variation in personal genomes using RegulomeDB (2012, background): “Recently, Ward and Kellis (2012) published the HaploReg database which aims to provide a similar annotation by providing an intersect of SNVs with chromatin state (Ernst and Kellis 2010).”