Role of non-coding sequence variants in cancer (original) (raw)
Kandoth, C. et al. Mutational landscape and significance across 12 major cancer types. Nature502, 333–339 (2013). CASPubMedPubMed Central Google Scholar
Easton, D. F. & Eeles, R. A. Genome-wide association studies in cancer. Hum. Mol. Genet.17, R109–R115 (2008). CASPubMed Google Scholar
Maurano, M. T. et al. Systematic localization of common disease-associated variation in regulatory DNA. Science337, 1190–1195 (2012). CASPubMedPubMed Central Google Scholar
Chen, C. Y., Chang, I. S., Hsiung, C. A. & Wasserman, W. W. On the identification of potential regulatory variants within genome wide association candidate SNP sets. BMC Med. Genomics7, 34 (2014). PubMedPubMed Central Google Scholar
Akhtar-Zaidi, B. et al. Epigenomic enhancer profiling defines a signature of colon cancer. Science336, 736–739 (2012). CASPubMedPubMed Central Google Scholar
Kron, K. J., Bailey, S. D. & Lupien, M. Enhancer alterations in cancer: a source for a cell identity crisis. Genome Med.6, 77 (2014). PubMedPubMed Central Google Scholar
Iyer, M. K. et al. The landscape of long noncoding RNAs in the human transcriptome. Nat. Genet.47, 199–208 (2015). CASPubMedPubMed Central Google Scholar
Stirzaker, C., Taberlay, P. C., Statham, A. L. & Clark, S. J. Mining cancer methylomes: prospects and challenges. Trends Genet.30, 75–84 (2014). CASPubMed Google Scholar
The 1000 Genomes Project Consortium. An integrated map of genetic variation from 1,092 human genomes. Nature491, 56–65 (2012).
Abyzov, A. et al. Somatic copy number mosaicism in human skin revealed by induced pluripotent stem cells. Nature492, 438–442 (2012). CASPubMedPubMed Central Google Scholar
De, S. Somatic mosaicism in healthy human tissues. Trends Genet.27, 217–223 (2011). CASPubMed Google Scholar
Lawrence, M. S. et al. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature499, 214–218 (2013). Shows how mutational heterogeneity in the genome can lead to false positives during the identification of cancer driver genes. CASPubMedPubMed Central Google Scholar
Horn, S. et al. TERT promoter mutations in familial and sporadic melanoma. Science339, 959–961 (2013). One of the first papers showing prevalence ofTERTpromoter mutations in cancer. CASPubMed Google Scholar
Daye, Z. J., Li, H. & Wei, Z. A powerful test for multiple rare variants association studies that incorporates sequencing qualities. Nucleic Acids Res.40, e60 (2012). CASPubMedPubMed Central Google Scholar
Stephens, P. J. et al. Massive genomic rearrangement acquired in a single catastrophic event during cancer development. Cell144, 27–40 (2011). CASPubMedPubMed Central Google Scholar
Holland, A. J. & Cleveland, D. W. Boveri revisited: chromosomal instability, aneuploidy and tumorigenesis. Nat. Rev. Mol. Cell Biol.10, 478–487 (2009). CASPubMedPubMed Central Google Scholar
Wittkopp, P. J. & Kalay, G. _Cis_-regulatory elements: molecular mechanisms and evolutionary processes underlying divergence. Nat. Rev. Genet.13, 59–69 (2012). CAS Google Scholar
Galas, D. J. & Schmitz, A. DNAse footprinting: a simple method for the detection of protein−DNA binding specificity. Nucleic Acids Res.5, 3157–3170 (1978). CASPubMedPubMed Central Google Scholar
Neph, S. et al. An expansive human regulatory lexicon encoded in transcription factor footprints. Nature489, 83–90 (2012). CASPubMedPubMed Central Google Scholar
Dunham, I. et al. An integrated encyclopedia of DNA elements in the human genome. Nature489, 57–74 (2012). Discussion of functional annotations from the ENCODE project. CAS Google Scholar
Hughes, J. R. et al. Analysis of hundreds of _cis_-regulatory landscapes at high resolution in a single, high-throughput experiment. Nat. Genet.46, 205–212 (2014). CASPubMed Google Scholar
de Laat, W. & Dekker, J. 3C-based technologies to study the shape of the genome. Methods58, 189–191 (2012). CASPubMed Google Scholar
Yip, K. Y. et al. Classification of human genomic regions based on experimentally determined binding sites of more than 100 transcription-related factors. Genome Biol.13, R48 (2012). CASPubMedPubMed Central Google Scholar
The GTEx Consortium. The Genotype-Tissue Expression (GTEx) pilot analysis: multitissue gene regulation in humans. Science348, 648–660 (2015).
Gerstein, M. B. et al. Architecture of the human regulatory network derived from ENCODE data. Nature489, 91–100 (2012). CASPubMedPubMed Central Google Scholar
Shalem, O. et al. Systematic dissection of the sequence determinants of gene 3′ end mediated expression control. PLoS Genet.11, e1005147 (2015). PubMedPubMed Central Google Scholar
Dvir, S. et al. Deciphering the rules by which 5′-UTR sequences affect protein expression in yeast. Proc. Natl Acad. Sci. USA110, E2792–E2801 (2013). CASPubMed Google Scholar
Lappalainen, T. et al. Transcriptome and genome sequencing uncovers functional variation in humans. Nature501, 506–511 (2013). CASPubMedPubMed Central Google Scholar
The GTEx Consortium. The Genotype-Tissue Expression (GTEx) project. Nat. Genet.45, 580–585 (2013).
Zhao, J., Sun, B. K., Erwin, J. A., Song, J. J. & Lee, J. T. Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome. Science322, 750–756 (2008). CASPubMedPubMed Central Google Scholar
Rinn, J. L. et al. Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell129, 1311–1323 (2007). CASPubMedPubMed Central Google Scholar
Penny, G. D., Kay, G. F., Sheardown, S. A., Rastan, S. & Brockdorff, N. Requirement for Xist in X chromosome inactivation. Nature379, 131–137 (1996). CASPubMed Google Scholar
Schmitz, K. M., Mayer, C., Postepska, A. & Grummt, I. Interaction of noncoding RNA with the rDNA promoter mediates recruitment of DNMT3b and silencing of rRNA genes. Genes Dev.24, 2264–2269 (2010). CASPubMedPubMed Central Google Scholar
Zhang, Z. et al. PseudoPipe: an automated pseudogene identification pipeline. Bioinformatics22, 1437–1439 (2006). CASPubMed Google Scholar
Khurana, E. et al. Segmental duplications in the human genome reveal details of pseudogene formation. Nucleic Acids Res.38, 6997–7007 (2010). CASPubMedPubMed Central Google Scholar
Sasidharan, R. & Gerstein, M. Genomics: protein fossils live on as RNA. Nature453, 729–731 (2008). CASPubMed Google Scholar
Tam, O. H. et al. Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes. Nature453, 534–538 (2008). CASPubMedPubMed Central Google Scholar
Loots, G. G. et al. Identification of a coordinate regulator of interleukins 4, 13, and 5 by cross-species sequence comparisons. Science288, 136–140 (2000). CASPubMed Google Scholar
Pennacchio, L. A. & Rubin, E. M. Genomic strategies to identify mammalian regulatory sequences. Nat. Rev. Genet.2, 100–109 (2001). CASPubMed Google Scholar
Waterston, R. H. et al. Initial sequencing and comparative analysis of the mouse genome. Nature420, 520–562 (2002). CASPubMed Google Scholar
Gibbs, R. A. et al. Genome sequence of the Brown Norway rat yields insights into mammalian evolution. Nature428, 493–521 (2004). CASPubMed Google Scholar
Lindblad-Toh, K. et al. Genome sequence, comparative analysis and haplotype structure of the domestic dog. Nature438, 803–819 (2005). CASPubMed Google Scholar
Bejerano, G. et al. Ultraconserved elements in the human genome. Science304, 1321–1325 (2004). CASPubMed Google Scholar
Peng, J. C., Shen, J. & Ran, Z. H. Transcribed ultraconserved region in human cancers. RNA Biol.10, 1771–1777 (2013). CASPubMedPubMed Central Google Scholar
Calin, G. A. et al. Ultraconserved regions encoding ncRNAs are altered in human leukemias and carcinomas. Cancer Cell12, 215–229 (2007). CASPubMed Google Scholar
Khurana, E. et al. Integrative annotation of variants from 1092 humans: application to cancer genomics. Science342, 1235587 (2013). One of the first methods for genome-wide identification of non-coding candidate cancer drivers. PubMedPubMed Central Google Scholar
Katzman, S. et al. Human genome ultraconserved elements are ultraselected. Science317, 915 (2007). CASPubMed Google Scholar
Ward, L. D. & Kellis, M. Evidence of abundant purifying selection in humans for recently acquired regulatory functions. Science337, 1675–1678 (2012). CASPubMedPubMed Central Google Scholar
Visel, A., Minovitsky, S., Dubchak, I. & Pennacchio, L. A. VISTA Enhancer Browser — a database of tissue-specific human enhancers. Nucleic Acids Res.35, D88–D92 (2007). CASPubMed Google Scholar
Weinhold, N., Jacobsen, A., Schultz, N., Sander, C. & Lee, W. Genome-wide analysis of noncoding regulatory mutations in cancer. Nat. Genet.46, 1160–1165 (2014). Analysis of hundreds of cancer whole-genomes to identify driver mutations in non-coding regions. CASPubMedPubMed Central Google Scholar
Fredriksson, N. J., Ny, L., Nilsson, J. A. & Larsson, E. Systematic analysis of noncoding somatic mutations and gene expression alterations across 14 tumor types. Nat. Genet.46, 1258–1263 (2014). CASPubMed Google Scholar
Smith, K. S. et al. Signatures of accelerated somatic evolution in gene promoters in multiple cancer types. Nucleic Acids Res.43, 5307–5317 (2015). CASPubMedPubMed Central Google Scholar
Melton, C., Reuter, J. A., Spacek, D. V. & Snyder, M. Recurrent somatic mutations in regulatory regions of human cancer genomes. Nat. Genet.47, 710–716 (2015). CASPubMedPubMed Central Google Scholar
Katainen, R. et al. CTCF/cohesin-binding sites are frequently mutated in cancer. Nat. Genet.47, 818–821 (2015). CASPubMed Google Scholar
Puente, X. S. et al. Non-coding recurrent mutations in chronic lymphocytic leukaemia. Nature526, 519–524 (2015). CASPubMed Google Scholar
Treangen, T. J. & Salzberg, S. L. Repetitive DNA and next-generation sequencing: computational challenges and solutions. Nat. Rev. Genet.13, 36–46 (2012). CAS Google Scholar
Mijuškovic´, M. et al. A streamlined method for detecting structural variants in cancer genomes by short read paired-end sequencing. PLoS ONE7, e48314 (2012). PubMedPubMed Central Google Scholar
Meyerson, M., Gabriel, S. & Getz, G. Advances in understanding cancer genomes through second-generation sequencing. Nat. Rev. Genet.11, 685–696 (2010). CASPubMed Google Scholar
Heidenreich, B., Rachakonda, P. S., Hemminki, K. & Kumar, R. TERT promoter mutations in cancer development. Curr. Opin. Genet. Dev.24, 30–37 (2014). CASPubMed Google Scholar
Huang, F. W. et al. Highly recurrent TERT promoter mutations in human melanoma. Science339, 957–959 (2013). One of the first papers showing prevalence ofTERTpromoter mutations in cancer. CASPubMedPubMed Central Google Scholar
Killela, P. J. et al. TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal. Proc. Natl Acad. Sci. USA110, 6021–6026 (2013). CASPubMed Google Scholar
Hnisz, D. et al. Super-enhancers in the control of cell identity and disease. Cell155, 934–947 (2013). CASPubMed Google Scholar
Mansour, M. R. et al. An oncogenic super-enhancer formed through somatic mutation of a noncoding intergenic element. Science346, 644–648 (2014). Google Scholar
Tomlins, S. A. et al. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science310, 1373–1377 (2005). Google Scholar
Yu, J. et al. An integrated network of androgen receptor, polycomb, and TMPRSS2_−_ERG gene fusions in prostate cancer progression. Cancer Cell17, 443–454 (2010). CASPubMedPubMed Central Google Scholar
Weischenfeldt, J. et al. Integrative genomic analyses reveal an androgen-driven somatic alteration landscape in early-onset prostate cancer. Cancer Cell23, 159–170 (2013). CASPubMed Google Scholar
Northcott, P. A. et al. Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma. Nature511, 428–434 (2014). CASPubMedPubMed Central Google Scholar
Breit, T. M. et al. Site-specific deletions involving the _tal_-1 and sil genes are restricted to cells of the T cell receptor α/β lineage: T cell receptor δ gene deletion mechanism affects multiple genes. J. Exp. Med.177, 965–977 (1993). CASPubMed Google Scholar
Nambiar, M., Kari, V. & Raghavan, S. C. Chromosomal translocations in cancer. Biochim. Biophys. Acta1786, 139–152 (2008). CASPubMed Google Scholar
Gutschner, T. & Diederichs, S. The hallmarks of cancer: a long non-coding RNA point of view. RNA Biol.9, 703–719 (2012). CASPubMedPubMed Central Google Scholar
Han, Y., Liu, Y., Nie, L., Gui, Y. & Cai, Z. Inducing cell proliferation inhibition, apoptosis, and motility reduction by silencing long noncoding ribonucleic acid metastasis-associated lung adenocarcinoma transcript 1 in urothelial carcinoma of the bladder. Urology81, 209.e1–209.e7 (2013). Google Scholar
Liu, P. Y. et al. Effects of a novel long noncoding RNA, lncUSMycN, on N-Myc expression and neuroblastoma progression. J. Natl Cancer Inst.106, dju113 (2014). PubMed Google Scholar
Buechner, J. & Einvik, C. N-myc and noncoding RNAs in neuroblastoma. Mol. Cancer Res.10, 1243–1253 (2012). CASPubMed Google Scholar
Lin, P. C. et al. Epigenetic repression of miR-31 disrupts androgen receptor homeostasis and contributes to prostate cancer progression. Cancer Res.73, 1232–1244 (2013). CASPubMed Google Scholar
Poliseno, L. et al. A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature465, 1033–1038 (2010). CASPubMedPubMed Central Google Scholar
Karreth, F. A. et al. The BRAF pseudogene functions as a competitive endogenous RNA and induces lymphoma in vivo. Cell161, 319–332 (2015). CASPubMed Google Scholar
Bahcall, O. G. iCOGS collection provides a collaborative model. Nat. Genet.45, 343 (2013). CASPubMed Google Scholar
MacArthur, D. G. et al. A systematic survey of loss-of-function variants in human protein-coding genes. Science335, 823–828 (2012). CASPubMedPubMed Central Google Scholar
Wang, Q., Lu, Q. & Zhao, H. A review of study designs and statistical methods for genomic epidemiology studies using next generation sequencing. Front. Genet.6, 149 (2015). PubMedPubMed Central Google Scholar
Bond, G. L. & Levine, A. J. A single nucleotide polymorphism in the p53 pathway interacts with gender, environmental stresses and tumor genetics to influence cancer in humans. Oncogene26, 1317–1323 (2007). CASPubMed Google Scholar
Bond, G. L. et al. A single nucleotide polymorphism in the MDM2 promoter attenuates the p53 tumor suppressor pathway and accelerates tumor formation in humans. Cell119, 591–602 (2004). CASPubMed 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). CASPubMed Google Scholar
Oldridge, D. A. et al. Genetic predisposition to neuroblastoma mediated by a LMO1 super-enhancer polymorphism. Nature528, 418–421 (2015). CASPubMedPubMed Central Google Scholar
Garritano, S. et al. In-silico identification and functional validation of allele-dependent AR enhancers. Oncotarget6, 4816–4828 (2015). PubMedPubMed Central Google Scholar
Bakker, J. L. et al. A novel splice site mutation in the noncoding region of BRCA2: implications for Fanconi anemia and familial breast cancer diagnostics. Hum. Mut.35, 442–446 (2014). CASPubMed Google Scholar
Demichelis, F. et al. Identification of functionally active, low frequency copy number variants at 15q21.3 and 12q21.31 associated with prostate cancer risk. Proc. Natl Acad. Sci. USA109, 6686–6691 (2012). CASPubMed Google Scholar
Chen, X. et al. Targeted resequencing of the microRNAome and 3′UTRome reveals functional germline DNA variants with altered prevalence in epithelial ovarian cancer. Oncogene34, 2125–2137 (2015). CASPubMed Google Scholar
Yang, Q. et al. Genetic variations in miR-27a gene decrease mature miR-27a level and reduce gastric cancer susceptibility. Oncogene33, 193–202 (2014). CASPubMed Google Scholar
Chu, M. C., Selam, F. B. & Taylor, H. S. HOXA10 regulates p53 expression and matrigel invasion in human breast cancer cells. Cancer Biol. Ther.3, 568–572 (2004). CASPubMed Google Scholar
Li, Q. et al. Integrative eQTL-based analyses reveal the biology of breast cancer risk loci. Cell152, 633–641 (2013). CASPubMedPubMed Central Google Scholar
Xu, X. et al. Variants at IRX4 as prostate cancer expression quantitative trait loci. Eur. J. Hum. Genet.22, 558–563 (2014). CASPubMed Google Scholar
Knudson, A. G. Mutation and cancer: statistical study of retinoblastoma. Proc. Natl Acad. Sci. USA68, 820–823 (1971). PubMed Google Scholar
Calin, G. A. et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc. Natl Acad. Sci. USA101, 2999–3004 (2004). CASPubMed Google Scholar
Pasic, I. et al. Recurrent focal copy-number changes and loss of heterozygosity implicate two noncoding RNAs and one tumor suppressor gene at chromosome 3q13.31 in osteosarcoma. Cancer Res.70, 160–171 (2010). CASPubMed Google Scholar
Rachakonda, P. S. et al. TERT promoter mutations in bladder cancer affect patient survival and disease recurrence through modification by a common polymorphism. Proc. Natl Acad. Sci. USA110, 17426–17431 (2013). CASPubMed Google Scholar
Gnad, F., Baucom, A., Mukhyala, K., Manning, G. & Zhang, Z. Assessment of computational methods for predicting the effects of missense mutations in human cancers. BMC Genomics14, S7 (2013). PubMedPubMed Central Google Scholar
Lee, S. et al. Optimal unified approach for rare-variant association testing with application to small-sample case−control whole-exome sequencing studies. Am. J. Hum. Genet.91, 224–237 (2012). CASPubMedPubMed Central Google Scholar
Tamborero, D. et al. Comprehensive identification of mutational cancer driver genes across 12 tumor types. Sci. Rep.3, 2650 (2013). PubMedPubMed Central Google Scholar
Lochovsky, L., Zhang, J., Fu, Y., Khurana, E. & Gerstein, M. LARVA: an integrative framework for large-scale analysis of recurrent variants in noncoding annotations. Nucleic Acids Res.43, 8123–8134 (2015). Method that accounts for heterogeneity in mutation rate in non-coding regions to identify regulatory driver mutations. CASPubMedPubMed Central Google Scholar
Ng, P. C. & Henikoff, S. SIFT: predicting amino acid changes that affect protein function. Nucleic Acids Res.31, 3812–3814 (2003). CASPubMedPubMed Central Google Scholar
Adzhubei, I. A. et al. A method and server for predicting damaging missense mutations. Nat. Methods7, 248–249 (2010). CASPubMedPubMed Central Google Scholar
Polak, P. et al. Cell-of-origin chromatin organization shapes the mutational landscape of cancer. Nature518, 360–364 (2015). Shows that somatic mutation density can be predicted based on epigenomic features from the cell of origin. CASPubMedPubMed Central Google Scholar
Fu, Y. et al. FunSeq2: a framework for prioritizing noncoding regulatory variants in cancer. Genome Biol.15, 480 (2014). PubMedPubMed Central Google Scholar
O'Roak, B. J. et al. Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders. Science41, 177–181 (2012). Google Scholar
Konermann, S. et al. Genome-scale transcriptional activation by an engineered CRISPR−Cas9 complex. Nature517, 583–588 (2014). PubMedPubMed Central Google Scholar
Mogno, I., Kwasnieski, J. C. & Cohen, B. A. Massively parallel synthetic promoter assays reveal the in vivo effects of binding site variants. Genome Res.23, 1908–1915 (2013). CASPubMedPubMed Central Google Scholar
Arnold, C. D. et al. Genome-wide quantitative enhancer activity maps identified by STARR-seq. Science339, 1074–1077 (2013). CASPubMed Google Scholar
Melnikov, A. et al. Systematic dissection and optimization of inducible enhancers in human cells using a massively parallel reporter assay. Nat. Biotechnol.30, 271–277 (2012). CASPubMedPubMed Central Google Scholar
Shlyueva, D., Stampfel, G. & Stark, A. Transcriptional enhancers: from properties to genome-wide predictions. Nat. Rev. Genet.15, 272–286 (2014). CASPubMed Google Scholar
Kwasnieski, J. C., Fiore, C., Chaudhari, H. G. & Cohen, B. A. High-throughput functional testing of ENCODE segmentation predictions. Genome Res.24, 1595–1602 (2014). CASPubMedPubMed Central Google Scholar
Singh, G. & Cooper, T. A. Minigene reporter for identification and analysis of cis elements and trans factors affecting pre-mRNA splicing. Biotechniques41, 177–181 (2006). CASPubMed Google Scholar
Gaildrat, P. et al. Use of splicing reporter minigene assay to evaluate the effect on splicing of unclassified genetic variants. Methods Mol. Biol.653, 249–257 (2010). CASPubMed Google Scholar
Poulos, R. C. et al. Systematic screening of promoter regions pinpoints functional _cis_-regulatory mutations in a cutaneous melanoma genome. Mol. Cancer Res.13, 1218–1226 (2015). CASPubMed Google Scholar
van de Wetering, M. et al. Prospective derivation of a living organoid biobank of colorectal cancer patients. Cell161, 933–945 (2015). CASPubMedPubMed Central Google Scholar
Boj, S. F. et al. Organoid models of human and mouse ductal pancreatic cancer. Cell160, 324–338 (2015). CASPubMed Google Scholar
Seruggia, D., Fernández, A., Cantero, M., Pelczar, P. & Montoliu, L. Functional validation of mouse tyrosinase non-coding regulatory DNA elements by CRISPR−Cas9-mediated mutagenesis. Nucleic Acids Res.43, 4855–4867 (2015). CASPubMedPubMed Central Google Scholar
Mou, H., Kennedy, Z., Anderson, D. G., Yin, H. & Xue, W. Precision cancer mouse models through genome editing with CRISPR−Cas9. Genome Med.7, 53 (2015). PubMedPubMed Central Google Scholar
The Cancer Genome Atlas Research Network. Comprehensive molecular profiling of lung adenocarcinoma. Nature511, 543–550 (2014).
Guenther, C. A., Tasic, B., Luo, L., Bedell, M. A. & Kingsley, D. M. A molecular basis for classic blond hair color in Europeans. Nat. Genet.46, 748–752 (2014). CASPubMedPubMed Central Google Scholar
Davoli, T. et al. Cumulative haploinsufficiency and triplosensitivity drive aneuploidy patterns and shape the cancer genome. Cell155, 948–962 (2013). CASPubMedPubMed Central Google Scholar
Xue, W. et al. A cluster of cooperating tumor-suppressor gene candidates in chromosomal deletions. Proc. Natl Acad. Sci. USA109, 8212–8217 (2012). CASPubMed Google Scholar
Wang, K. et al. Whole-genome sequencing and comprehensive molecular profiling identify new driver mutations in gastric cancer. Nat. Genet.46, 573–582 (2014). CASPubMed Google Scholar
Chelala, C., Khan, A. & Lemoine, N. R. SNPnexus: a web database for functional annotation of newly discovered and public domain single nucleotide polymorphisms. Bioinformatics25, 655–661 (2009). CASPubMed Google Scholar
Dayem Ullah, A. Z., Lemoine, N. R. & Chelala, C. SNPnexus: a web server for functional annotation of novel and publicly known genetic variants (2012 update). Nucleic Acids Res.40, W65–W70 (2012). CASPubMedPubMed Central Google Scholar
Wang, K., Li, M. & Hakonarson, H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res.38, e164 (2010). PubMedPubMed Central Google Scholar
McLaren, W. et al. Deriving the consequences of genomic variants with the Ensembl API and SNP Effect Predictor. Bioinformatics26, 2069–2070 (2010). CASPubMedPubMed Central Google Scholar
Perera, D. et al. OncoCis: annotation of _cis_-regulatory mutations in cancer. Genome Biol.15, 485 (2014). PubMedPubMed Central Google Scholar
Paila, U., Chapman, B. A., Kirchner, R. & Quinlan, A. R. GEMINI: integrative exploration of genetic variation and genome annotations. PLoS Comput. Biol.9, e1003153 (2013). CASPubMedPubMed Central Google Scholar
Coetzee, S. G., Rhie, S. K., Berman, B. P., Coetzee, G. A. & Noushmehr, H. FunciSNP: an R/bioconductor tool integrating functional non-coding data sets with genetic association studies to identify candidate regulatory SNPs. Nucleic Acids Res.40, e139 (2012). CASPubMedPubMed Central Google Scholar
Ward, L. D. & Kellis, M. HaploReg: a resource for exploring chromatin states, conservation, and regulatory motif alterations within sets of genetically linked variants. Nucleic Acids Res.40, D930–D934 (2012). CASPubMed Google Scholar
Li, M. J., Wang, L. Y., Xia, Z., Sham, P. C. & Wang, J. GWAS3D: detecting human regulatory variants by integrative analysis of genome-wide associations, chromosome interactions and histone modifications. Nucleic Acids Res.41, W150–W158 (2013). PubMedPubMed Central Google Scholar
Macintyre, G., Bailey, J., Haviv, I. & Kowalczyk, A. is-rSNP: a novel technique for in silico regulatory SNP detection. Bioinformatics26, i524–i530 (2010). CASPubMedPubMed Central Google Scholar
Boyle, A. P. et al. Annotation of functional variation in personal genomes using RegulomeDB. Genome Res.22, 1790–1797 (2012). CASPubMedPubMed Central Google Scholar
Lehmann, K. V. & Chen, T. Exploring functional variant discovery in non-coding regions with SInBaD. Nucleic Acids Res.41, e7 (2013). CASPubMed Google Scholar
Kircher, M. et al. A general framework for estimating the relative pathogenicity of human genetic variants. Nat. Genet.46, 310–315 (2014). CASPubMedPubMed Central Google Scholar
Ritchie, G. R., Dunham, I., Zeggini, E. & Flicek, P. Functional annotation of noncoding sequence variants. Nat. Methods11, 294–296 (2014). CASPubMedPubMed Central Google Scholar
Gulko, B., Hubisz, M. J., Gronau, I. & Siepel, A. A method for calculating probabilities of fitness consequences for point mutations across the human genome. Nat. Genet.47, 276–283 (2015). CASPubMedPubMed Central Google Scholar
Zhou, J. & Troyanskaya, O. G. Predicting effects of noncoding variants with deep learning-based sequence model. Nat. Methods12, 931–934 (2015). CASPubMedPubMed Central Google Scholar