Candidate gene association studies: A comprehensive guide to useful in silico tools

BMC Genetics

Volumn 14, Issue , 2013, Pages

  Patnala, Radhika ^a   Clements, Judith ^a   Batra, Jyotsna ^a  

^a QUEENSLAND UNIVERSITY OF TECHNOLOGY   (Australia)

Author keywords

Association studies; Cancer; Candidate gene; In silico; LD; SNP

Indexed keywords

ANDROGEN; COMPLEMENTARY DNA; ESTROGEN; KRUPPEL LIKE FACTOR 6; MESSENGER RNA;

AMINO ACID SEQUENCE; AUTISM; BINDING SITE; COMPUTER MODEL; DISEASE ASSOCIATION; GENE LOCATION; GENE MAPPING; GENETIC ANALYSIS; GENETIC ASSOCIATION; GENETIC RISK; GENETIC VARIABILITY; GENOTYPE; HAPLOTYPE; HIGH THROUGHPUT SCREENING; PHENOTYPE; PHYLOGENY; PROSTATE CANCER; PROTEIN EXPRESSION; PROTEIN STRUCTURE; QUANTITATIVE TRAIT LOCUS; REVIEW; RISK ASSESSMENT; SCHIZOPHRENIA; SEQUENCE ANALYSIS; SINGLE NUCLEOTIDE POLYMORPHISM;

COMPUTER SIMULATION; GENOME-WIDE ASSOCIATION STUDY; HUMANS; QUANTITATIVE TRAIT LOCI; REGULATORY SEQUENCES, NUCLEIC ACID;

EID: 84877141942     PISSN: None     EISSN: 14712156     Source Type: Journal    
DOI: 10.1186/1471-2156-14-39     Document Type: Review

References (139)

1. Kwon JM, Goate AM. The candidate gene approach. Alcohol Res Health 2000, 24(3):164-168.
2. Collins FS, Guyer MS, Chakravarti A. Variations on a theme: cataloging human DNA sequence variation. Science 1997, 278(5343):1580-1581.
3. Peters BJM, Rodin AS, De Boer A, Maitland-van der Zee A-H. Methodological and statistical issues in pharmacogenomics. J Pharm Pharmacol 2010, 62(2):161-166.
4. Burdick KE, DeRosse P, Kane JM, Lencz T, Malhotra AK. Genetic variation in the MET proto-oncogene is associated with schizophrenia and general cognitive ability. Am J Psychiatry 2010, 167(4):436-443.
5. Gibbs RA, Belmont JW, Hardenbol P, Willis TD, Yu F, Yang H, Ch'ang L-Y, Huang W, Liu B, Shen Y. The international HapMap project. Nature 2003, 426(6968):789-796.
6. An integrated map of genetic variation from 1,092 human genomes. Nature 2012, 491(7422):56-65.
7. Pharoah PDP, Dunning AM, Ponder BAJ, Easton DF. Association studies for finding cancer-susceptibility genetic variants. Nat Rev Cancer 2004, 4(11):850-860.
8. Braem MGM, Schouten LJ, Peeters PHM, den Brandt PA, Onland-Moret NC. Genetic susceptibility to sporadic ovarian cancer: A systematic review. Biochimica et Biophysica Acta (BBA) - Rev Cancer 2011, 1816(2):132-146.
9. Tabor HK, Risch NJ, Myers RM. Candidate-gene approaches for studying complex genetic traits: practical considerations. Nat Rev Genet 2002, 3(5):391-397.
10. Fernández J, Hoffmann R, Valencia A. iHOP Web Services Family. Bioinformatics for personalized medicine 2012, 102-107. Berlin Heidelberg: Springer, Freitas A, Navarro A, vol. 6620.
11. Hokamp K, Wolfe KH. PubCrawler: keeping up comfortably with PubMed and GenBank. Nucleic Acids Res 2004, 32(suppl 2):W16-W19.
12. Mastellos D, Andronis C, Persidis A, Lambris JD. Novel biological networks modulated by complement. Clin Immunol 2005, 115(3):225-235.
13. Croft D, O'Kelly G, Wu G, Haw R, Gillespie M, Matthews L, Caudy M, Garapati P, Gopinath G, Jassal B. Reactome: a database of reactions, pathways and biological processes. Nucleic Acids Res 2011, 39(suppl 1):D691-D697.
14. Frisch M, Klocke B, Haltmeier M, Frech K. LitInspector: literature and signal transduction pathway mining in PubMed abstracts. Nucleic Acids Res 2009, 37(suppl 2):W135-W140.
15. Kandasamy K, Mohan SS, Raju R, Keerthikumar S, Kumar G, Venugopal A, Telikicherla D, Navarro JD, Mathivanan S, Pecquet C. NetPath: a public resource of curated signal transduction pathways. Genome Biol 2010, 11(1):R3.
16. Haibe-Kains B, Olsen C, Djebbari A, Bontempi G, Correll M, Bouton C, Quackenbush J. Predictive networks: a flexible, open source, web application for integration and analysis of human gene networks. Nucleic Acids Res 2012, 40(D1):D866-D875.
17. Chen J, Bardes EE, Aronow BJ, Jegga AG. ToppGene Suite for gene list enrichment analysis and candidate gene prioritization. Nucleic Acids Res 2009, 37(suppl 2):W305-W311.
18. Tranchevent L-C, Capdevila FB, Nitsch D, De Moor B, De Causmaecker P, Moreau Y. A guide to web tools to prioritize candidate genes. Brief Bioinform 2011, 12(1):22-32.
19. Amberger J, Bocchini C, Hamosh A. A new face and new challenges for online Mendelian inheritance in man (OMIM®). Hum Mutat 2011, 32(5):564-567.
20. Radivojac P, Peng K, Clark WT, Peters BJ, Mohan A, Boyle SM, Mooney SD. An integrated approach to inferring gene-disease associations in humans. Proteins: Structure, Function, and Bioinformatics 2008, 72(3):1030-1037.
21. Rhodes DR, Kalyana-Sundaram S, Mahavisno V, Varambally R, Yu J, Briggs BB, Barrette TR, Anstet MJ, Kincead-Beal C, Kulkarni P. Oncomine 3.0: genes, pathways, and networks in a collection of 18,000 cancer gene expression Profiles1 2007, New York (NY): Neoplasia Press Inc.
22. Hu P, Bader G, Wigle DA, Emili A. Computational prediction of cancer-gene function. Nat Rev Cancer 2007, 7(1):23-34.
23. Wheeler DL, Barrett T, Benson DA, Bryant SH, Canese K, Church DM, DiCuccio M, Edgar R, Federhen S, Helmberg W. Database resources of the national center for biotechnology information. Nucleic Acids Res 2005, 33(suppl 1):D39-D45.
24. Hubbard TJP, Aken BL, Ayling S, Ballester B, Beal K, Bragin E, Brent S, Chen Y, Clapham P, Clarke L. Ensembl 2009. Nucleic Acids Res 2009, 37(suppl 1):D690-D697.
25. Batra J, Nagle C, O'Mara T, Higgins M, Dong Y, Tan O, Lose F, Skeie L, Srinivasan S, Bolton K. A Kallikrein 15 (KLK15) single nucleotide polymorphism located close to a novel exon shows evidence of association with poor ovarian cancer survival. BMC Cancer 2011, 11(1):119.
26. Narla G, DiFeo A, Reeves HL, Schaid DJ, Hirshfeld J, Hod E, Katz A, Isaacs WB, Hebbring S, Komiya A. A Germline DNA polymorphism enhances alternative splicing of the KLF6 tumor suppressor gene and is associated with increased prostate cancer risk. Cancer Res 2005, 65(4):1213-1222.
27. Thierry-Mieg D, Thierry-Mieg J. AceView: a comprehensive cDNA-supported gene and transcripts annotation. Genome Biol 2006, 7(Suppl 1):S12.
28. Kuhn RM, Karolchik D, Zweig AS, Wang T, Smith KE, Rosenbloom KR, Rhead B, Raney BJ, Pohl A, Pheasant M. The UCSC genome browser database: update 2009. Nucleic Acids Res 2009, 37(suppl 1):D755-D761.
29. The EPC. A User's guide to the encyclopedia of DNA elements (ENCODE). PLoS Biol 2011, 9(4):e1001046.
30. Frazer KA, Pachter L, Poliakov A, Rubin EM, Dubchak I. VISTA: computational tools for comparative genomics. Nucleic Acids Res 2004, 32(suppl 2):W273-W279.
31. Visel A, Minovitsky S, Dubchak I, Pennacchio LA. VISTA enhancer browser-a database of tissue-specific human enhancers. Nucleic Acids Res 2007, 35(suppl 1):D88-D92.
32. Lukashin I, Novichkov P, Boffelli D, Paciorkowski AR, Minovitsky S, Yang S, Dubchak I. VISTA region viewer (RViewer)-a computational system for prioritizing genomic intervals for biomedical studies. Bioinformatics 2011, 27(18):2595-2597.
33. Chen Y-H, Liu C-K, Chang S-C, Lin Y-J, Tsai M-F, Chen Y-T, Yao A. GenoWatch: a disease gene mining browser for association study. Nucleic Acids Res 2008, 36(suppl 2):W336-W340.
34. Mooney SD, Krishnan VG, Evani US. Bioinformatic tools for identifying disease gene and SNP candidates. Genetic Variation 2010, 307-319. : Humana Press, Barnes MR, Breen G, vol. 628.
35. Batra J, O'Mara T, Patnala R, Lose F, Clements JA. Genetic polymorphisms in the human tissue kallikrein (KLK) locus and their implication in various malignant and non-malignant diseases. Biol Chem 2012, 393:1365.
36. Coassin S, Brandstätter A, Kronenberg F. Lost in the space of bioinformatic tools: a constantly updated survival guide for genetic epidemiology. The GenEpi toolbox. Atherosclerosis 2010, 209(2):321-335.
37. Sherry ST, Ward M-H, Kholodov M, Baker J, Phan L, Smigielski EM, Sirotkin K. dbSNP: the NCBI database of genetic variation. Nucleic Acids Res 2001, 29(1):308-311.
38. Church DM, Lappalainen I, Sneddon TP, Hinton J, Maguire M, Lopez J, Garner J, Paschall J, DiCuccio M, Yaschenko E. Public data archives for genomic structural variation. Nat Genet 2010, 42(10):813-814.
39. Chen K, McLellan MD, Ding L, Wendl MC, Kasai Y, Wilson RK, Mardis ER. PolyScan: an automatic indel and SNP detection approach to the analysis of human resequencing data. Genome Res 2007, 17(5):659-666.
40. Saccone SF, Quan J, Jones PL. BioQ: tracing experimental origins in public genomic databases using a novel data provenance model. Bioinformatics 2012, 28(8):1189-1191.
41. Saccone SF, Quan J, Mehta G, Bolze R, Thomas P, Deelman E, Tischfield JA, Rice JP. New tools and methods for direct programmatic access to the dbSNP relational database. Nucleic Acids Res 2011, 39(suppl 1):D901-D907.
42. Riva A, Kohane IS. SNPper: retrieval and analysis of human SNPs. Bioinformatics 2002, 18(12):1681-1685.
43. Andersen MC, Engström PG, Lithwick S, Arenillas D, Eriksson P, Lenhard B, Wasserman WW, Odeberg J. In silico detection of sequence variations modifying transcriptional regulation. PLoS Comput Biol 2008, 4(1):e5.
44. Packer BR, Yeager M, Staats B, Welch R, Crenshaw A, Kiley M, Eckert A, Beerman M, Miller E, Bergen A. SNP500Cancer: a public resource for sequence validation and assay development for genetic variation in candidate genes. Nucleic Acids Res 2004, 32(suppl 1):D528-D532.
45. Wang K, Li M, Hakonarson H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res 2010, 38(16):e164.
46. Xu Z, Taylor JA. SNPinfo: integrating GWAS and candidate gene information into functional SNP selection for genetic association studies. Nucleic Acids Res 2009, 37(suppl 2):W600-W605.
47. Weiss KM, Clark AG. Linkage disequilibrium and the mapping of complex human traits. Trends in Genetics 2002, 18(1):19-24.
48. Ardlie KG, Kruglyak L, Seielstad M. Patterns of linkage disequilibrium in the human genome. Nat Rev Genet 2002, 3(4):299-309.
49. Slatkin M. Linkage disequilibrium [mdash] understanding the evolutionary past and mapping the medical future. Nat Rev Genet 2008, 9(6):477-485.
50. Pallejà A, Horn H, Eliasson S, Jensen LJ. DistiLD Database: diseases and traits in linkage disequilibrium blocks. Nucleic Acids Res 2012, 40(D1):D1036-D1040.
51. Lawrence R, Day-Williams A, Mott R, Broxholme J, Cardon L, Zeggini E. GLIDERS - A web-based search engine for genome-wide linkage disequilibrium between HapMap SNPs. BMC Bioinforma 2009, 10(1):367.
52. Yoo J, Lee Y, Kim Y, Rha S, Kim Y. SNPAnalyzer 2.0: a web-based integrated workbench for linkage disequilibrium analysis and association analysis. BMC Bioinforma 2008, 9(1):290.
53. Johnson AD, Handsaker RE, Pulit SL, Nizzari MM, O'Donnell CJ, de Bakker PIW. SNAP: a web-based tool for identification and annotation of proxy SNPs using HapMap. Bioinformatics 2008, 24(24):2938-2939.
54. A compilation of some available software for linkage disequilibrium analysis. http://www.genes.org.uk/software/LD-software.shtml.
55. Barrett JC, Fry B, Maller J, Daly MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 2005, 21(2):263-265.
56. Jackson DG, Healy MD, Davison DB. Binformatics: not just for sequences anymore. BIOSILICO 2003, 1(3):103-111.
57. Maurano MT, Humbert R, Rynes E, Thurman RE, Haugen E, Wang H, Reynolds AP, Sandstrom R, Qu H, Brody J. Systematic localization of common disease-associated variation in regulatory DNA. Science 2012, 337(6099):1190-1195.
58. Wang X, Tomso DJ, Liu X, Bell DA. Single nucleotide polymorphism in transcriptional regulatory regions and expression of environmentally responsive genes. Toxicol Appl Pharmacol 2005, 207(2, Supplement):84-90.
59. Prokunina L, Alarcón-Riquelme ME. Regulatory SNPs in complex diseases: their identification and functional validation. Expert Reviews in Molecular Medicine 2004, 6(10):1-15.
60. GuhaThakurta D, Xie T, Anand M, Edwards S, Li G, Wang S, Schadt E. Cis-regulatory variations: a study of SNPs around genes showing cis-linkage in segregating mouse populations. BMC Genomics 2006, 7(1):235.
61. Muinos-Gimeno M, Montfort M, Bayes M, Estivill X, Espinosa-Parrilla Y. Design and evaluation of a panel of single-nucleotide polymorphisms in microRNA genomic regions for association studies in human disease. Eur J Hum Genet 2009, 18(2):218-226.
62. McLaren W, Pritchard B, Rios D, Chen Y, Flicek P, Cunningham F. Deriving the consequences of genomic variants with the Ensembl API and SNP Effect Predictor. Bioinformatics 2010, 26(16):2069-2070.
63. Cooper GM, Shendure J. Needles in stacks of needles: finding disease-causal variants in a wealth of genomic data. Nat Rev Genet 2011, 12(9):628-640.
64. Jiang L, Zhang C, Li Y, Yu X, Zheng J, Zou P, Li Y, Bin X, Lu J, Zhou Y. A non-synonymous polymorphism Thr115Met in the EpCAM gene is associated with an increased risk of breast cancer in Chinese population. Breast Cancer Res Treat 2011, 126(2):487-495.
65. Yue P, Melamud E, Moult J. SNPs3D: candidate gene and SNP selection for association studies. BMC Bioinformatics 2006, 7(1):1-15.
66. Ryan M, Diekhans M, Lien S, Liu Y, Karchin R. LS-SNP/PDB: annotated non-synonymous SNPs mapped to Protein Data Bank structures. Bioinformatics 2009, 25(11):1431-1432.
67. Pieper U, Webb BM, Barkan DT, Schneidman-Duhovny D, Schlessinger A, Braberg H, Yang Z, Meng EC, Pettersen EF, Huang CC. ModBase, a database of annotated comparative protein structure models, and associated resources. Nucleic Acids Res 2011, 39(suppl 1):D465-D474.
68. Jegga AG, Gowrisankar S, Chen J, Aronow BJ. PolyDoms: a whole genome database for the identification of non-synonymous coding SNPs with the potential to impact disease. Nucleic Acids Res 2007, 35(suppl 1):D700-D706.
69. Consortium TU Reorganizing the protein space at the universal protein resource (UniProt). Nucleic Acids Res 2012, 40(D1):D71-D75. Consortium TU.
70. De Baets G, Van Durme J, Reumers J, Maurer-Stroh S, Vanhee P, Dopazo J, Schymkowitz J, Rousseau F. SNPeffect 4.0: on-line prediction of molecular and structural effects of protein-coding variants. Nucleic Acids Res 2012, 40(D1):D935-D939.
71. Conde L, Vaquerizas JM, Dopazo H, Arbiza L, Reumers J, Rousseau F, Schymkowitz J, Dopazo J. PupaSuite: finding functional single nucleotide polymorphisms for large-scale genotyping purposes. Nucleic Acids Res 2006, 34(suppl 2):W621-W625.
72. Mah JTL, Low ESH, Lee E. In silico SNP analysis and bioinformatics tools: a review of the state of the art to aid drug discovery. Drug Discov Today 2011, 16(17-18):800-809.
73. Mah JTL, Low ESH, Lee E. In silico SNP analysis and bioinformatics tools: a review of the state of the art to aid drug discovery. Drug discovery today 2011, 16(17):800-809.
74. Miller MP, Kumar S. Understanding human disease mutations through the use of interspecific genetic variation. Hum Mol Genet 2001, 10(21):2319-2328.
75. Kwasigroch JM, Gilis D, Dehouck Y, Rooman M. PoPMuSiC, rationally designing point mutations in protein structures. Bioinformatics 2002, 18(12):1701-1702.
76. Mort M, Evani US, Krishnan VG, Kamati KK, Baenziger PH, Bagchi A, Peters BJ, Sathyesh R, Li B, Sun Y. In silico functional profiling of human disease-associated and polymorphic amino acid substitutions. Hum Mutat 2010, 31(3):335-346.
77. Sunyaev S, Ramensky V, Bork P. Towards a structural basis of human non-synonymous single nucleotide polymorphisms. Trends in Genetics 2000, 16(5):198-200.
78. Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, Kondrashov AS, Sunyaev SR. A method and server for predicting damaging missense mutations. Nat Meth 2010, 7(4):248-249.
79. Kumar P, Henikoff S, Ng PC. Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat Protocols 2009, 4(8):1073-1081.
80. Choi Y, Sims GE, Murphy S, Miller JR, Chan AP. Predicting the functional effect of amino acid substitutions and Indels. PLoS ONE 2012, 7(10):e46688.
81. Li S, Iakoucheva LM, Mooney SD, Radivojac P. Loss of post-translational modification sites in disease. Pac Symp Biocomput 2010, 337-347. : World Scientific.
82. Mann M, Jensen ON. Proteomic analysis of post-translational modifications. Nat Biotech 2003, 21(3):255-261.
83. Blom N, Gammeltoft S, Brunak S. Sequence and structure-based prediction of eukaryotic protein phosphorylation sites. J Mol Biol 1999, 294(5):1351-1362.
84. Sigrist CJA, Cerutti L, de Castro E, Langendijk-Genevaux PS, Bulliard V, Bairoch A, Hulo N. PROSITE, a protein domain database for functional characterization and annotation. Nucleic Acids Res 2010, 38(suppl 1):D161-D166.
85. Werner T. Functional in silico analysis of Non-coding SNPs 2003, 273-287. Chichester, UK: John Wiley & Sons, Ltd, Bioinformatics for geneticists.
86. Boyle AP, Davis S, Shulha HP, Meltzer P, Margulies EH, Weng Z, Furey TS, Crawford GE. High-resolution mapping and characterization of open chromatin across the genome. Cell 2008, 132(2):311-322.
87. Gaspar-Maia A, Alajem A, Meshorer E, Ramalho-Santos M. Open chromatin in pluripotency and reprogramming. Nat Rev Mol Cell Biol 2011, 12(1):36-47.
88. Tsunoda T, Takagi T. Estimating transcription factor bindability on DNA. Bioinformatics 1999, 15(7):622-630.
89. Cartharius K, Frech K, Grote K, Klocke B, Haltmeier M, Klingenhoff A, Frisch M, Bayerlein M, Werner T. MatInspector and beyond: promoter analysis based on transcription factor binding sites. Bioinformatics 2005, 21(13):2933-2942.
90. Heinemeyer T, Wingender E, Reuter I, Hermjakob H, Kel AE, Kel OV, Ignatieva EV, Ananko EA, Podkolodnaya OA, Kolpakov FA. Databases on transcriptional regulation: TRANSFAC, TRRD and COMPEL. Nucleic Acids Res 1998, 26(1):362-367.
91. Marinescu VD, Kohane IS, Riva A. The MAPPER database: a multi-genome catalog of putative transcription factor binding sites. Nucleic Acids Res 2005, 33(suppl 1):D91-D97.
92. Macintyre G, Bailey J, Haviv I, Kowalczyk A. Is-rSNP: a novel technique for in silico regulatory SNP detection. Bioinformatics 2010, 26(18):i524-i530.
93. Boyle AP, Hong EL, Hariharan M, Cheng Y, Schaub MA, Kasowski M, Karczewski KJ, Park J, Hitz BC, Weng S. Annotation of functional variation in personal genomes using RegulomeDB. Genome Res 2012, 22(9):1790-1797.
94. Coetzee SG, Rhie SK, Berman BP, Coetzee GA, 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 2012, 40(18):e139.
95. Hazelett DJ, Coetzee SG, Coetzee GA. A rare variant, which destroys a FoxA1 site at 8q24, is associated with prostate cancer risk. Cell Cycle 2013, 12(2):379-380.
96. Risch HA. Hormonal etiology of epithelial ovarian cancer, with a hypothesis concerning the role of androgens and progesterone. J Natl Cancer Inst 1998, 90(23):1774-1786.
97. Bajic VB, Tan SL, Chong A, Tang S, Ström A, Gustafsson J-T, Lin C-Y, Liu ET. Dragon ERE Finder version 2: a tool for accurate detection and analysis of estrogen response elements in vertebrate genomes. Nucleic Acids Res 2003, 31(13):3605-3607.
98. Portales-Casamar E, Thongjuea S, Kwon AT, Arenillas D, Zhao X, Valen E, Yusuf D, Lenhard B, Wasserman WW, Sandelin A. JASPAR 2010: the greatly expanded open-access database of transcription factor binding profiles. Nucleic Acids Res 2010, 38(suppl 1):D105-D110.
99. Frith MC, Hansen U, Weng Z. Detection of cis -element clusters in higher eukaryotic DNA. Bioinform 2001, 17(10):878-889.
100. Freedman ML, Monteiro ANA, Gayther SA, Coetzee GA, Risch A, Plass C, Casey G, De Biasi M, Carlson C, Duggan D. Principles for the post-GWAS functional characterization of cancer risk loci. Nat Genet 2011, 43(6):513-518.
101. Mishra PJ, Mishra PJ, Banerjee D, Bertino JR. MiRSNPs or MiR-polymorphisms, new players in microRNA mediated regulation of the cell: Introducing microRNA pharmacogenomics. Cell Cycle 2008, 7(7):853-858.
102. Sun G, Yan J, Noltner K, Feng J, Li H, Sarkis DA, Sommer SS, Rossi JJ. SNPs in human miRNA genes affect biogenesis and function. RNA 2009, 15(9):1640-1651.
103. Davis-Dusenbery BN, Hata A. MicroRNA in cancer: the involvement of aberrant MicroRNA biogenesis regulatory pathways. Genes & Cancer 2010, 1(11):1100-1114.
104. Betel D, Wilson M, Gabow A, Marks DS, Sander C. The microRNA.org resource: targets and expression. Nucleic Acids Res 2008, 36(suppl 1):D149-D153.
105. Kozomara A, Griffiths-Jones S. miRBase: integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res 2011, 39(suppl 1):D152-D157.
106. Thomas LF, Saito T, Sætrom P. Inferring causative variants in microRNA target sites. Nucleic Acids Res 2011, 39(16):e109.
107. Liu C, Zhang F, Li T, Lu M, Wang L, Yue W, Zhang D. MirSNP, a database of polymorphisms altering miRNA target sites, identifies miRNA-related SNPs in GWAS SNPs and eQTLs. BMC Genom 2012, 13(1):661.
108. Betel D, Koppal A, Agius P, Sander C, Leslie C. Comprehensive modeling of microRNA targets predicts functional non-conserved and non-canonical sites. Genome Biol 2010, 11(8):R90.
109. Ziebarth JD, Bhattacharya A, Chen A, Cui Y. PolymiRTS Database 2.0: linking polymorphisms in microRNA target sites with human diseases and complex traits. Nucleic Acids Res 2012, 40(D1):D216-D221.
110. Hiard S, Charlier C, Coppieters W, Georges M, Baurain D. Patrocles: a database of polymorphic miRNA-mediated gene regulation in vertebrates. Nucleic Acids Res 2010, 38(suppl 1):D640-D651.
111. Gilad Y, Rifkin SA, Pritchard JK. Revealing the architecture of gene regulation: the promise of eQTL studies. Trends Genet 2008, 24(8):408-415.
112. Jansen RC, Nap J-P. Genetical genomics: the added value from segregation. Trends Genet 2001, 17(7):388-391.
113. Jansen RC. Studying complex biological systems using multifactorial perturbation. Nat Rev Genet 2003, 4(2):145-151.
114. Wu C, Delano DL, Mitro N, Su SV, Janes J, McClurg P, Batalov S, Welch GL, Zhang J, Orth AP. Gene Set enrichment in eQTL data identifies novel annotations and pathway regulators. PLoS Genet 2008, 4(5):e1000070.
115. Wittkopp PJ. Genomic sources of regulatory variation in cis and in trans. Cell Mol Life Sci 2005, 62(16):1779-1783.
116. Li H, Deng H. Systems genetics, bioinformatics and eQTL mapping. Genetica 2010, 138(9):915-924.
117. Mueller M, Goel A, Thimma M, Dickens NJ, Aitman TJ, Mangion J. eQTL Explorer: integrated mining of combined genetic linkage and expression experiments. Bioinform 2006, 22(4):509-511.
118. Wang J, Williams R, Manly K. WebQTL. Neuroinform 2003, 1(4):299-308.
119. Seaton G, Haley CS, Knott SA, Kearsey M, Visscher PM. QTL Express: mapping quantitative trait loci in simple and complex pedigrees. Bioinform 2002, 18(2):339-340.
120. Zou W, Aylor D, Zeng Z-B. eQTL Viewer: visualizing how sequence variation affects genome-wide transcription. BMC Bioinform 2007, 8(1):7.
121. Gatti DM, Shabalin AA, Lam T-C, Wright FA, Rusyn I, Nobel AB. FastMap: Fast eQTL mapping in homozygous populations. Bioinform 2009, 25(4):482-489.
122. Lee S-I, Dudley AM, Drubin D, Silver PA, Krogan NJ, Pe'er D, Koller D. Learning a prior on regulatory potential from eQTL data. PLoS Genet 2009, 5(1):e1000358.
123. Giacomini KM, Brett CM, Altman RB, Benowitz NL, Dolan ME, Flockhart DA, Johnson JA, Hayes DF, Klein T, Krauss RM. The Pharmacogenetics research network: from SNP discovery to clinical drug response. Clin Pharmacol Ther 2007, 81(3):328-345.
124. Hawkins RD, Hon GC, Ren B. Next-generation genomics: an integrative approach. Nat Rev Genet 2010, 11(7):476-486.
125. Horgan R, Kenny L. 'Omic'technologies: genomics, transcriptomics, proteomics and metabolomics. The Obstetrician & Gynaecologist 2011, 13(3):189-195.
126. Cartegni L, Wang J, Zhu Z, Zhang MQ, Krainer AR. ESEfinder: a web resource to identify exonic splicing enhancers. Nucleic Acids Res 2003, 31(13):3568-3571.
127. Smith PJ, Zhang C, Wang J, Chew SL, Zhang MQ, Krainer AR. An increased specificity score matrix for the prediction of SF2/ASF-specific exonic splicing enhancers. Hum Mol Genet 2006, 15(16):2490-2508.
128. Goren A, Ram O, Amit M, Keren H, Lev-Maor G, Vig I, Pupko T, Ast G. Comparative analysis identifies exonic splicing regulatory sequences the complex definition of enhancers and silencers. Mol Cell 2006, 22(6):769-781.
129. Wang Z, Rolish ME, Yeo G, Tung V, Mawson M, Burge CB. Systematic identification and analysis of exonic splicing silencers. Cell 2004, 119(6):831-845.
130. Zhang XH-F, Chasin LA. Computational definition of sequence motifs governing constitutive exon splicing. Genes Dev 2004, 18(11):1241-1250.
131. Fairbrother WG, Yeh R-F, Sharp PA, Burge CB. Predictive identification of exonic splicing enhancers in human genes. Science 2002, 297(5583):1007-1013.
132. Desmet F-O, Hamroun D, Lalande M, Collod-Béroud G, Claustres M, Béroud C. Human splicing finder: an online bioinformatics tool to predict splicing signals. Nucleic Acids Res 2009, 37(9):e67.
133. Ok Yang J, Kim W-Y, Bhak J. ssSNPTarget: genome-wide splice-site single nucleotide polymorphism database. Hum Mutat 2009, 30(12):E1010-E1020.
134. Ahmed F, Kumar M, Raghava GPS. Prediction of polyadenylation signals in human DNA sequences using nucleotide frequencies. In Silico Biol 2009, 9(3):135-148.
135. Tabaska JE, Zhang MQ. Detection of polyadenylation signals in human DNA sequences. Gene 1999, 231(1-2):77-86.
136. Zuker M. Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Res 2003, 31(13):3406-3415.
137. Reeder J, Steffen P, Giegerich R. pknotsRG: RNA pseudoknot folding including near-optimal structures and sliding windows. Nucleic Acids Res 2007, 35(suppl 2):W320-W324.
138. Reeder J, Höchsmann M, Rehmsmeier M, Voss B, Giegerich R. Beyond Mfold: Recent advances in RNA bioinformatics. J Biotechnol 2006, 124(1):41-55.
139. Lambert A, Fontaine J-F, Legendre M, Leclerc F, Permal E, Major F, Putzer H, Delfour O, Michot B, Gautheret D. The ERPIN server: an interface to profile-based RNA motif identification. Nucleic Acids Res 2004, 32(suppl 2):W160-W165.