{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T07:28:59Z","timestamp":1778657339339,"version":"3.51.4"},"reference-count":56,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,5,17]],"date-time":"2016-05-17T00:00:00Z","timestamp":1463443200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,5,17]],"date-time":"2016-05-17T00:00:00Z","timestamp":1463443200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["61502272"],"award-info":[{"award-number":["61502272"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["61572284"],"award-info":[{"award-number":["61572284"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the Scientific Research Reward Foundation for Excellent Young and Middle-age Scientists of Shandong Province","award":["BS2014DX004"],"award-info":[{"award-number":["BS2014DX004"]}]},{"name":"the Opening Laboratory Fund of Qufu Normal University","award":["sk201416"],"award-info":[{"award-number":["sk201416"]}]},{"name":"the Science and Technology Planning Project of Qufu Normal University","award":["xkj201410"],"award-info":[{"award-number":["xkj201410"]}]},{"name":"the Scientific Research Foundation of Qufu Normal University","award":["BSQD20130119"],"award-info":[{"award-number":["BSQD20130119"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Bioinformatics"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Detecting and visualizing nonlinear interaction effects of single nucleotide polymorphisms (SNPs) or epistatic interactions are important topics in bioinformatics since they play an important role in unraveling the mystery of \u201cmissing heritability\u201d. However, related studies are almost limited to pairwise epistatic interactions due to their methodological and computational challenges.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We develop CINOEDV (Co-Information based<jats:italic>N<\/jats:italic>-Order Epistasis Detector and Visualizer) for the detection and visualization of epistatic interactions of their orders from 1 to<jats:italic>n<\/jats:italic>(<jats:italic>n<\/jats:italic>\u2009\u2265\u20092). CINOEDV is composed of two stages, namely, detecting stage and visualizing stage. In detecting stage, co-information based measures are employed to quantify association effects of<jats:italic>n<\/jats:italic>-order SNP combinations to the phenotype, and two types of search strategies are introduced to identify<jats:italic>n<\/jats:italic>-order epistatic interactions: an exhaustive search and a particle swarm optimization based search. In visualizing stage, all detected<jats:italic>n<\/jats:italic>-order epistatic interactions are used to construct a hypergraph, where a real vertex represents the main effect of a SNP and a virtual vertex denotes the interaction effect of an<jats:italic>n<\/jats:italic>-order epistatic interaction. By deeply analyzing the constructed hypergraph, some hidden clues for better understanding the underlying genetic architecture of complex diseases could be revealed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Experiments of CINOEDV and its comparison with existing state-of-the-art methods are performed on both simulation data sets and a real data set of age-related macular degeneration. Results demonstrate that CINOEDV is promising in detecting and visualizing<jats:italic>n<\/jats:italic>-order epistatic interactions. CINOEDV is implemented in R and is freely available from R CRAN:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/cran.r-project.org\/\">http:\/\/cran.r-project.org<\/jats:ext-link>and<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/sourceforge.net\/projects\/cinoedv\/files\/\">https:\/\/sourceforge.net\/projects\/cinoedv\/files\/<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12859-016-1076-8","type":"journal-article","created":{"date-parts":[[2016,5,17]],"date-time":"2016-05-17T01:53:24Z","timestamp":1463450004000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["CINOEDV: a co-information based method for detecting and visualizing n-order epistatic interactions"],"prefix":"10.1186","volume":"17","author":[{"given":"Junliang","family":"Shang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingxia","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin-Xing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junfeng","family":"Xia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junying","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun-Hou","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,5,17]]},"reference":[{"issue":"7265","key":"1076_CR1","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1038\/nature08494","volume":"461","author":"TA Manolio","year":"2009","unstructured":"Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, Hunter DJ, McCarthy MI, Ramos EM, Cardon LR, Chakravarti A. Finding the missing heritability of complex diseases. Nature. 2009;461(7265):747\u201353.","journal-title":"Nature"},{"issue":"23","key":"1076_CR2","doi-asserted-by":"publisher","first-page":"9362","DOI":"10.1073\/pnas.0903103106","volume":"106","author":"LA Hindorff","year":"2009","unstructured":"Hindorff LA, Sethupathy P, Junkins HA, Ramos EM, Mehta JP, Collins FS, Manolio TA. Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc Natl Acad Sci. 2009;106(23):9362\u20137.","journal-title":"Proc Natl Acad Sci"},{"issue":"2","key":"1076_CR3","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1007\/s00439-013-1377-1","volume":"133","author":"P Jia","year":"2014","unstructured":"Jia P, Zhao Z. Network-assisted analysis to prioritize GWAS results: principles, methods and perspectives. Hum Genet. 2014;133(2):125\u201338.","journal-title":"Hum Genet"},{"issue":"6","key":"1076_CR4","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1038\/ng.f.136","volume":"40","author":"W Bodmer","year":"2008","unstructured":"Bodmer W, Bonilla C. Common and rare variants in multifactorial susceptibility to common diseases. Nat Genet. 2008;40(6):695\u2013701.","journal-title":"Nat Genet"},{"issue":"4","key":"1076_CR5","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1038\/nrg2554","volume":"10","author":"KA Frazer","year":"2009","unstructured":"Frazer KA, Murray SS, Schork NJ, Topol EJ. Human genetic variation and its contribution to complex traits. Nat Rev Genet. 2009;10(4):241\u201351.","journal-title":"Nat Rev Genet"},{"issue":"6","key":"1076_CR6","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1038\/nrg2809","volume":"11","author":"EE Eichler","year":"2010","unstructured":"Eichler EE, Flint J, Gibson G, Kong A, Leal SM, Moore JH, Nadeau JH. Missing heritability and strategies for finding the underlying causes of complex disease. Nat Rev Genet. 2010;11(6):446\u201350.","journal-title":"Nat Rev Genet"},{"issue":"7218","key":"1076_CR7","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1038\/456018a","volume":"456","author":"B Maher","year":"2008","unstructured":"Maher B. The case of the missing heritability. Nature. 2008;456(7218):18\u201321.","journal-title":"Nature"},{"issue":"20","key":"1076_CR8","doi-asserted-by":"publisher","first-page":"2463","DOI":"10.1093\/hmg\/11.20.2463","volume":"11","author":"HJ Cordell","year":"2002","unstructured":"Cordell HJ. Epistasis: what it means, what it doesn't mean, and statistical methods to detect it in humans. Hum Mol Genet. 2002;11(20):2463\u20138.","journal-title":"Hum Mol Genet"},{"issue":"11","key":"1076_CR9","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1038\/nrg2452","volume":"9","author":"PC Phillips","year":"2008","unstructured":"Phillips PC. Epistasis\u2014the essential role of gene interactions in the structure and evolution of genetic systems. Nat Rev Genet. 2008;9(11):855\u201367.","journal-title":"Nat Rev Genet"},{"issue":"6","key":"1076_CR10","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1038\/nrg2579","volume":"10","author":"HJ Cordell","year":"2009","unstructured":"Cordell HJ. Detecting gene\u2013gene interactions that underlie human diseases. Nat Rev Genet. 2009;10(6):392\u2013404.","journal-title":"Nat Rev Genet"},{"issue":"11","key":"1076_CR11","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1038\/nrg3747","volume":"15","author":"W-H Wei","year":"2014","unstructured":"Wei W-H, Hemani G, Haley CS. Detecting epistasis in human complex traits. Nat Rev Genet. 2014;15(11):722\u201333.","journal-title":"Nat Rev Genet"},{"issue":"24","key":"1076_CR12","doi-asserted-by":"publisher","first-page":"3275","DOI":"10.1093\/bioinformatics\/btp596","volume":"25","author":"C Herold","year":"2009","unstructured":"Herold C, Steffens M, Brockschmidt FF, Baur MP, Becker T. INTERSNP: genome-wide interaction analysis guided by a priori information. Bioinformatics. 2009;25(24):3275\u201381.","journal-title":"Bioinformatics"},{"issue":"1","key":"1076_CR13","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1086\/321276","volume":"69","author":"MD Ritchie","year":"2001","unstructured":"Ritchie MD, Hahn LW, Roodi N, Bailey LR, Dupont WD, Parl FF, Moore JH. Multifactor-dimensionality reduction reveals high-order interactions among estrogen-metabolism genes in sporadic breast cancer. Am J Hum Genet. 2001;69(1):138.","journal-title":"Am J Hum Genet"},{"issue":"4","key":"1076_CR14","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1093\/bioinformatics\/btp713","volume":"26","author":"JH Moore","year":"2010","unstructured":"Moore JH, Asselbergs FW, Williams SM. Bioinformatics challenges for genome-wide association studies. Bioinformatics. 2010;26(4):445\u201355.","journal-title":"Bioinformatics"},{"issue":"12","key":"1076_CR15","doi-asserted-by":"publisher","first-page":"i217","DOI":"10.1093\/bioinformatics\/btq186","volume":"26","author":"X Zhang","year":"2010","unstructured":"Zhang X, Huang S, Zou F, Wang W. TEAM: efficient two-locus epistasis tests in human genome-wide association study. Bioinformatics. 2010;26(12):i217\u201327.","journal-title":"Bioinformatics"},{"issue":"3","key":"1076_CR16","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/j.ajhg.2010.07.021","volume":"87","author":"X Wan","year":"2010","unstructured":"Wan X, Yang C, Yang Q, Xue H, Fan X, Tang NLS, Yu W. BOOST: A fast approach to detecting gene-gene interactions in genome-wide case\u2013control studies. Am J Hum Genet. 2010;87(3):325.","journal-title":"Am J Hum Genet"},{"issue":"1","key":"1076_CR17","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1093\/bioinformatics\/btp622","volume":"26","author":"X Wan","year":"2010","unstructured":"Wan X, Yang C, Yang Q, Xue H, Tang NL, Yu W. Predictive rule inference for epistatic interaction detection in genome-wide association studies. Bioinformatics. 2010;26(1):30\u20137.","journal-title":"Bioinformatics"},{"issue":"1","key":"1076_CR18","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1186\/1756-0500-3-117","volume":"3","author":"Y Wang","year":"2010","unstructured":"Wang Y, Liu X, Robbins K, Rekaya R. AntEpiSeeker: detecting epistatic interactions for case\u2013control studies using a two-stage ant colony optimization algorithm. BMC Res Notes. 2010;3(1):117.","journal-title":"BMC Res Notes"},{"issue":"9","key":"1076_CR19","doi-asserted-by":"publisher","first-page":"1167","DOI":"10.1038\/ng2110","volume":"39","author":"Y Zhang","year":"2007","unstructured":"Zhang Y, Liu JS. Bayesian inference of epistatic interactions in case\u2013control studies. Nat Genet. 2007;39(9):1167\u201373.","journal-title":"Nat Genet"},{"issue":"5","key":"1076_CR20","doi-asserted-by":"publisher","first-page":"e1000464","DOI":"10.1371\/journal.pgen.1000464","volume":"5","author":"W Tang","year":"2009","unstructured":"Tang W, Wu X, Jiang R, Li Y. Epistatic module detection for case\u2013control studies: a Bayesian model with a Gibbs sampling strategy. PLoS Genet. 2009;5(5):e1000464.","journal-title":"PLoS Genet"},{"issue":"10","key":"1076_CR21","doi-asserted-by":"publisher","first-page":"1274","DOI":"10.1038\/ejhg.2009.38","volume":"17","author":"P Chanda","year":"2009","unstructured":"Chanda P, Sucheston L, Zhang A, Ramanathan M. The interaction index, a novel information-theoretic metric for prioritizing interacting genetic variations and environmental factors. Eur J Hum Genet. 2009;17(10):1274\u201386.","journal-title":"Eur J Hum Genet"},{"issue":"2","key":"1076_CR22","doi-asserted-by":"publisher","first-page":"1191","DOI":"10.1534\/genetics.108.088542","volume":"180","author":"P Chanda","year":"2008","unstructured":"Chanda P, Sucheston L, Zhang A, Brazeau D, Freudenheim JL, Ambrosone C, Ramanathan M. AMBIENCE: a novel approach and efficient algorithm for identifying informative genetic and environmental associations with complex phenotypes. Genetics. 2008;180(2):1191\u2013210.","journal-title":"Genetics"},{"issue":"5","key":"1076_CR23","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1086\/521878","volume":"81","author":"P Chanda","year":"2007","unstructured":"Chanda P, Zhang A, Brazeau D, Sucheston L, Freudenheim JL, Ambrosone C, Ramanathan M. Information-theoretic metrics for visualizing gene-environment interactions. Am J Hum Gen. 2007;81(5):939\u201363.","journal-title":"Am J Hum Gen"},{"issue":"1","key":"1076_CR24","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1186\/1471-2164-10-509","volume":"10","author":"P Chanda","year":"2009","unstructured":"Chanda P, Sucheston L, Liu S, Zhang A, Ramanathan M. Information-theoretic gene-gene and gene-environment interaction analysis of quantitative traits. BMC Genomics. 2009;10(1):509.","journal-title":"BMC Genomics"},{"issue":"1","key":"1076_CR25","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1186\/1471-2164-11-487","volume":"11","author":"L Sucheston","year":"2010","unstructured":"Sucheston L, Chanda P, Zhang A, Tritchler D, Ramanathan M. Comparison of information-theoretic to statistical methods for gene-gene interactions in the presence of genetic heterogeneity. BMC Genomics. 2010;11(1):487.","journal-title":"BMC Genomics"},{"key":"1076_CR26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.dsp.2013.08.007","volume":"24","author":"J Shang","year":"2014","unstructured":"Shang J, Zhang J, Sun Y, Zhang Y. EpiMiner: A three-stage co-information based method for detecting and visualizing epistatic interactions. Digital Signal Processing. 2014;24:1\u201313.","journal-title":"Digital Signal Processing"},{"issue":"7","key":"1076_CR27","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1002\/gepi.21754","volume":"37","author":"Y Wu","year":"2013","unstructured":"Wu Y, Zhu X, Chen J, Zhang X. EINVis: a visualization tool for analyzing and exploring genetic interactions in large-scale association studies. Genet Epidemiol. 2013;37(7):675\u201385.","journal-title":"Genet Epidemiol"},{"issue":"2","key":"1076_CR28","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1016\/j.jtbi.2005.11.036","volume":"241","author":"JH Moore","year":"2006","unstructured":"Moore JH, Gilbert JC, Tsai C-T, Chiang F-T, Holden T, Barney N, White BC. A flexible computational framework for detecting, characterizing, and interpreting statistical patterns of epistasis in genetic studies of human disease susceptibility. J Theor Biol. 2006;241(2):252\u201361.","journal-title":"J Theor Biol"},{"issue":"3","key":"1076_CR29","doi-asserted-by":"publisher","first-page":"e1000432","DOI":"10.1371\/journal.pgen.1000432","volume":"5","author":"BA McKinney","year":"2009","unstructured":"McKinney BA, Crowe JE, Guo J, Tian D. Capturing the spectrum of interaction effects in genetic association studies by simulated evaporative cooling network analysis. PLoS Genet. 2009;5(3):e1000432.","journal-title":"PLoS Genet"},{"issue":"8","key":"1076_CR30","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1038\/gene.2010.37","volume":"11","author":"N Davis","year":"2010","unstructured":"Davis N, Crowe J, Pajewski N, McKinney B. Surfing a genetic association interaction network to identify modulators of antibody response to smallpox vaccine. Genes Immun. 2010;11(8):630\u20136.","journal-title":"Genes Immun"},{"issue":"8","key":"1076_CR31","doi-asserted-by":"publisher","first-page":"e154","DOI":"10.1038\/tp.2012.80","volume":"2","author":"A Pandey","year":"2012","unstructured":"Pandey A, Davis N, White B, Pajewski N, Savitz J, Drevets W, McKinney B. Epistasis network centrality analysis yields pathway replication across two GWAS cohorts for bipolar disorder. Transl Psychiatry. 2012;2(8):e154.","journal-title":"Transl Psychiatry"},{"issue":"6","key":"1076_CR32","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1002\/gepi.21739","volume":"37","author":"NA Davis","year":"2013","unstructured":"Davis NA, Lareau CA, White BC, Pandey A, Wiley G, Montgomery CG, Gaffney PM, McKinney B. Encore: Genetic association interaction network centrality pipeline and application to sle exome data. Genet Epidemiol. 2013;37(6):614\u201321.","journal-title":"Genet Epidemiol"},{"key":"1076_CR33","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1186\/1471-2105-12-364","volume":"12","author":"T Hu","year":"2011","unstructured":"Hu T, Sinnott-Armstrong NA, Kiralis JW, Andrew AS, Karagas MR, Moore JH. Characterizing genetic interactions in human disease association studies using statistical epistasis networks. BMC Bioinformatics. 2011;12:364.","journal-title":"BMC Bioinformatics"},{"issue":"1","key":"1076_CR34","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/1756-0381-7-5","volume":"7","author":"T Hu","year":"2014","unstructured":"Hu T, Pan Q, Andrew AS, Langer JM, Cole MD, Tomlinson CR, Karagas MR, Moore JH. Functional genomics annotation of a statistical epistasis network associated with bladder cancer susceptibility. BioData Mining. 2014;7(1):5.","journal-title":"BioData Mining"},{"issue":"12","key":"1076_CR35","doi-asserted-by":"publisher","first-page":"e51301","DOI":"10.1371\/journal.pone.0051301","volume":"7","author":"AS Andrew","year":"2012","unstructured":"Andrew AS, Hu T, Gu J, Gui J, Ye Y, Marsit CJ, Kelsey KT, Schned AR, Tanyos SA, Pendleton EM. HSD3B and gene-gene interactions in a pathway-based analysis of genetic susceptibility to bladder cancer. PLoS One. 2012;7(12):e51301.","journal-title":"PLoS One"},{"issue":"1","key":"1076_CR36","first-page":"11","volume":"5","author":"NA Lavender","year":"2012","unstructured":"Lavender NA, Rogers EN, Yeyeodu S, Rudd J, Hu T, Zhang J, Brock GN, Kimbro KS, Moore JH, Hein DW. Interaction among apoptosis-associated sequence variants and joint effects on aggressive prostate cancer. BMC Med Genet. 2012;5(1):11.","journal-title":"BMC Med Genet"},{"key":"1076_CR37","doi-asserted-by":"crossref","unstructured":"Hu T, Andrew AS, Karagas MR, Moore JH: Statistical epistasis networks reduce the computational complexity of searching three-locus genetic models. In: Pac Symp Biocomput: 2013. World Scientific: 397\u2013408.","DOI":"10.1142\/9789814447973_0039"},{"issue":"3","key":"1076_CR38","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1002\/gepi.21718","volume":"37","author":"T Hu","year":"2013","unstructured":"Hu T, Chen Y, Kiralis JW, Moore JH. ViSEN: methodology and software for visualization of statistical epistasis networks. Genet Epidemiol. 2013;37(3):283\u20135.","journal-title":"Genet Epidemiol"},{"key":"1076_CR39","unstructured":"Bell AJ: The co-information lattice. The 4th International Symposium on Independent Component Analysis and Blind Signal Separation 2003:921\u2013926."},{"issue":"1","key":"1076_CR40","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/S0019-9958(80)90478-7","volume":"46","author":"T Sun Han","year":"1980","unstructured":"Sun Han T. Multiple mutual informations and multiple interactions in frequency data. Inf Control. 1980;46(1):26\u201345.","journal-title":"Inf Control"},{"key":"1076_CR41","unstructured":"James K, Russell E: Particle swarm optimization. In: Proceedings of 1995 IEEE International Conference on Neural Networks: 1995. 1942\u20131948."},{"issue":"5","key":"1076_CR42","doi-asserted-by":"publisher","first-page":"468","DOI":"10.7763\/IJMLC.2014.V4.456","volume":"4","author":"M-L Hwang","year":"2014","unstructured":"Hwang M-L, Lin Y-D, Chuang L-Y, Yang C-H. Determination of the SNP-SNP Interaction between Breast Cancer Related Genes to Analyze the Disease Susceptibility. Int J Mach Learn Comput. 2014;4(5):468\u201373.","journal-title":"Int J Mach Learn Comput"},{"key":"1076_CR43","doi-asserted-by":"crossref","unstructured":"Tizhoosh HR. Opposition-Based Learning: A New Scheme for Machine Intelligence. In: Proceedings of International Conference on Computational Intelligence for Modelling, Control and Automation 2006 and International Conference on Intelligent Agents, Web Technologies and Internet Commerce 2006. Vienna: IEEE Press; 2005. p. 695\u2013701.","DOI":"10.1109\/CIMCA.2005.1631345"},{"key":"1076_CR44","doi-asserted-by":"crossref","unstructured":"Shang J, Zhang J, Lei X, Zhao W, Dong Y. EpiSIM: simulation of multiple epistasis, linkage disequilibrium patterns and haplotype blocks for genome-wide interaction analysis. Genes Genomics 2013;35(3):305-16.","DOI":"10.1007\/s13258-013-0081-9"},{"issue":"1","key":"1076_CR45","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12859-015-0525-0","volume":"16","author":"L Parida","year":"2015","unstructured":"Parida L, Haiminen N. SimBA: simulation algorithm to fit extant-population distributions. BMC bioinformatics. 2015;16(1):1.","journal-title":"BMC bioinformatics"},{"key":"1076_CR46","doi-asserted-by":"crossref","unstructured":"Haiminen N, Lebreton C, Parida L: Best-fit in linear time for non-generative population simulation. In: Algorithms in Bioinformatics. Wroclaw, Poland: Springer; 2014: 247\u2013262.","DOI":"10.1007\/978-3-662-44753-6_19"},{"issue":"1","key":"1076_CR47","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1186\/1471-2105-12-475","volume":"12","author":"J Shang","year":"2011","unstructured":"Shang J, Zhang J, Sun Y, Liu D, Ye D, Yin Y. Performance analysis of novel methods for detecting epistasis. BMC Bioinformatics. 2011;12(1):475.","journal-title":"BMC Bioinformatics"},{"issue":"3","key":"1076_CR48","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1007\/s13258-012-0003-2","volume":"34","author":"J Shang","year":"2012","unstructured":"Shang J, Zhang J, Lei X, Zhang Y, Chen B. Incorporating heuristic information into ant colony optimization for epistasis detection. Genes Genomics. 2012;34(3):321\u20137.","journal-title":"Genes Genomics"},{"issue":"6","key":"1076_CR49","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1038\/hdy.2014.4","volume":"112","author":"M Aflakparast","year":"2014","unstructured":"Aflakparast M, Salimi H, Gerami A, Dub\u00e9 M, Visweswaran S, Masoudi-Nejad A. Cuckoo search epistasis: a new method for exploring significant genetic interactions. Heredity. 2014;112(6):666\u201374.","journal-title":"Heredity"},{"issue":"1","key":"1076_CR50","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1756-0381-4-21","volume":"4","author":"DS Himmelstein","year":"2011","unstructured":"Himmelstein DS, Greene CS, Moore JH. Evolving hard problems: generating human genetics datasets with a complex etiology. BioData Mining. 2011;4(1):1\u201313.","journal-title":"BioData Mining"},{"issue":"5720","key":"1076_CR51","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1126\/science.1109557","volume":"308","author":"RJ Klein","year":"2005","unstructured":"Klein RJ, Zeiss C, Chew EY, Tsai JY, Sackler RS, Haynes C, Henning AK, SanGiovanni JP, Mane SM, Mayne ST. Complement factor H polymorphism in age-related macular degeneration. Science. 2005;308(5720):385\u20139.","journal-title":"Science"},{"issue":"20","key":"1076_CR52","doi-asserted-by":"publisher","first-page":"2517","DOI":"10.1093\/bioinformatics\/btq486","volume":"26","author":"X Wan","year":"2010","unstructured":"Wan X, Yang C, Yang Q, Xue H, Tang NL, Yu W. Detecting two-locus associations allowing for interactions in genome-wide association studies. Bioinformatics. 2010;26(20):2517\u201325.","journal-title":"Bioinformatics"},{"issue":"1","key":"1076_CR53","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1093\/bioinformatics\/btr603","volume":"28","author":"M Xie","year":"2012","unstructured":"Xie M, Li J, Jiang T. Detecting genome-wide epistases based on the clustering of relatively frequent items. Bioinformatics. 2012;28(1):5\u201312.","journal-title":"Bioinformatics"},{"key":"1076_CR54","doi-asserted-by":"crossref","unstructured":"Liao Z, Zeng Q, Liao B, Li X. A Novel Two-Stage Approach for Epistasis Detection in Genome-Wide Case\u2013Control Studies. Biochemical Genetics 2014;52(9-10):403-14.","DOI":"10.1007\/s10528-014-9656-7"},{"issue":"6","key":"1076_CR55","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1159\/000022939","volume":"50","author":"W Li","year":"2000","unstructured":"Li W, Reich J. A complete enumeration and classification of two-locus disease models. Hum Hered. 2000;50(6):334\u201349.","journal-title":"Hum Hered"},{"issue":"4","key":"1076_CR56","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1038\/ng1296-371","volume":"14","author":"WN Frankel","year":"1996","unstructured":"Frankel WN, Schork NJ. Who\u2019s afraid of epistasis? Nat Genet. 1996;14(4):371\u20133.","journal-title":"Nat Genet"}],"container-title":["BMC Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12859-016-1076-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12859-016-1076-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12859-016-1076-8","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12859-016-1076-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T14:40:54Z","timestamp":1748961654000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/s12859-016-1076-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,5,17]]},"references-count":56,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,12]]}},"alternative-id":["1076"],"URL":"https:\/\/doi.org\/10.1186\/s12859-016-1076-8","relation":{},"ISSN":["1471-2105"],"issn-type":[{"value":"1471-2105","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5,17]]},"assertion":[{"value":"26 November 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 May 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 May 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"214"}}