A method to predict the impact of regulatory variants from DNA sequence (original) (raw)

• Hindorff, L.A. et al. Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc. Natl. Acad. Sci. USA 106, 9362–9367 (2009).
  CAS PubMed PubMed Central Google Scholar
• Maurano, M.T. et al. Systematic localization of common disease-associated variation in regulatory DNA. Science 337, 1190–1195 (2012).
  CAS PubMed PubMed Central Google Scholar
• Gusev, A. et al. Partitioning heritability of regulatory and cell-type-specific variants across 11 common diseases. Am. J. Hum. Genet. 95, 535–552 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Kircher, M. et al. A general framework for estimating the relative pathogenicity of human genetic variants. Nat. Genet. 46, 310–315 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Ritchie, G.R.S., Dunham, I., Zeggini, E. & Flicek, P. Functional annotation of noncoding sequence variants. Nat. Methods 11, 294–296 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Hardison, R.C. & Taylor, J. Genomic approaches towards finding _cis_-regulatory modules in animals. Nat. Rev. Genet. 13, 469–483 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Ghandi, M., Lee, D., Mohammad-Noori, M. & Beer, M.A. Enhanced regulatory sequence prediction using gapped _k_-mer features. PLoS Comput. Biol. 10, e1003711 (2014).
  Article PubMed PubMed Central Google Scholar
• ENCODE Consortium. An integrated encyclopedia of DNA elements in the human genome. Nature 489, 57–74 (2012).
• Bernstein, B.E. et al. The NIH Roadmap Epigenomics Mapping Consortium. Nat. Biotechnol. 28, 1045–1048 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Lee, D., Karchin, R. & Beer, M.A. Discriminative prediction of mammalian enhancers from DNA sequence. Genome Res. 21, 2167–2180 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Fletez-Brant, C., Lee, D., McCallion, A.S. & Beer, M.A. kmer-SVM: a web server for identifying predictive regulatory sequence features in genomic data sets. Nucleic Acids Res. 41, W544–W556 (2013).
  Article PubMed PubMed Central Google Scholar
• Gorkin, D.U. et al. Integration of ChIP-seq and machine learning reveals enhancers and a predictive regulatory sequence vocabulary in melanocytes. Genome Res. 22, 2290–2301 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Degner, J.F. et al. DNase I sensitivity QTLs are a major determinant of human expression variation. Nature 482, 390–394 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• 1000 Genomes Project Consortium. A map of human genome variation from population-scale sequencing. Nature 467, 1061–1073 (2010).
• International HapMap Consortium. A haplotype map of the human genome. Nature 437, 1299–1320 (2005).
• Davydov, E.V. et al. Identifying a high fraction of the human genome to be under selective constraint using GERP++. PLoS Comput. Biol. 6, e1001025 (2010).
  Article PubMed PubMed Central Google Scholar
• Lee, D. & Beer, M.A. in Genome Analysis: Current Procedures and Applications (ed. Poptsova, M.S.) 101–120 (Horizon Scientific Press, 2014).
• Ghandi, M., Mohammad-Noori, M. & Beer, M. A. Robust _k_-mer frequency estimation using gapped _k_-mers. J. Math. Biol. 69, 469–500 (2014).
  Article PubMed Google Scholar
• Pickrell, J.K. et al. Understanding mechanisms underlying human gene expression variation with RNA sequencing. Nature 464, 768–772 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Murisier, F., Guichard, S. & Beermann, F. A conserved transcriptional enhancer that specifies Tyrp1 expression to melanocytes. Dev. Biol. 298, 644–655 (2006).
  Article CAS PubMed Google Scholar
• Murisier, F., Guichard, S. & Beermann, F. The tyrosinase enhancer is activated by Sox10 and Mitf in mouse melanocytes. Pigment Cell Res. 20, 173–184 (2007).
  Article CAS PubMed Google Scholar
• Patwardhan, R.P. et al. Massively parallel functional dissection of mammalian enhancers in vivo. Nat. Biotechnol. 30, 265–270 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Yue, F. et al. A comparative encyclopedia of DNA elements in the mouse genome. Nature 515, 355–364 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Kheradpour, P. et al. Systematic dissection of regulatory motifs in 2000 predicted human enhancers using a massively parallel reporter assay. Genome Res. 23, 800–811 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Huang, Q. et al. A prostate cancer susceptibility allele at 6q22 increases RFX6 expression by modulating HOXB13 chromatin binding. Nat. Genet. 46, 126–135 (2014).
  Article CAS PubMed Google Scholar
• Bauer, D.E. et al. An erythroid enhancer of BCL11A subject to genetic variation determines fetal hemoglobin level. Science 342, 253–257 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Musunuru, K. et al. From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus. Nature 466, 714–719 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Farh, K.K.-H. et al. Genetic and epigenetic fine mapping of causal autoimmune disease variants. Nature 518, 337–343 (2015).
  Article CAS PubMed Google Scholar
• Jin, Y. et al. Genome-wide association analyses identify 13 new susceptibility loci for generalized vitiligo. Nat. Genet. 44, 676–680 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Barrett, J.C. et al. Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nat. Genet. 41, 703–707 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Franke, A. et al. Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci. Nat. Genet. 42, 1118–1125 (2010).
  CAS PubMed PubMed Central Google Scholar
• Barrett, J.C. et al. Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease. Nat. Genet. 40, 955–962 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• International Multiple Sclerosis Genetics Consortium. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis. Nat. Genet. 45, 1353–1360 (2013).
• Dubois, P.C.A. et al. Multiple common variants for celiac disease influencing immune gene expression. Nat. Genet. 42, 295–302 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Parkes, M. et al. Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn's disease susceptibility. Nat. Genet. 39, 830–832 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Hinds, D.A. et al. A genome-wide association meta-analysis of self-reported allergy identifies shared and allergy-specific susceptibility loci. Nat. Genet. 45, 907–911 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Mells, G.F. et al. Genome-wide association study identifies 12 new susceptibility loci for primary biliary cirrhosis. Nat. Genet. 43, 329–332 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Trynka, G. et al. Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease. Nat. Genet. 43, 1193–1201 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Eyre, S. et al. High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis. Nat. Genet. 44, 1336–1340 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Cooper, J.D. et al. Seven newly identified loci for autoimmune thyroid disease. Hum. Mol. Genet. 21, 5202–5208 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Gourraud, P.-A. et al. A genome-wide association study of brain lesion distribution in multiple sclerosis. Brain 136, 1012–1024 (2013).
  Article PubMed PubMed Central Google Scholar
• Liu, J.Z. et al. Dense fine-mapping study identifies new susceptibility loci for primary biliary cirrhosis. Nat. Genet. 44, 1137–1141 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Zhang, Y. et al. Model-based Analysis of ChIP-Seq (MACS). Genome Biol. 9, R137 (2008).
  Article PubMed PubMed Central Google Scholar
• Heintzman, N.D. et al. Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome. Nat. Genet. 39, 311–318 (2007).
  Article CAS PubMed Google Scholar
• Heintzman, N.D. et al. Histone modifications at human enhancers reflect global cell-type-specific gene expression. Nature 459, 108–112 (2009).
  Article CAS PubMed PubMed Central Google Scholar