{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T02:48:54Z","timestamp":1773283734612,"version":"3.50.1"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"24","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Motivation: Not individual single nucleotide polymorphisms (SNPs), but high-order interactions of SNPs are assumed to be responsible for complex diseases such as cancer. Therefore, one of the major goals of genetic association studies concerned with such genotype data is the identification of these high-order interactions. This search is additionally impeded by the fact that these interactions often are only explanatory for a relatively small subgroup of patients. Most of the feature selection methods proposed in the literature, unfortunately, fail at this task, since they can either only identify individual variables or interactions of a low order, or try to find rules that are explanatory for a high percentage of the observations. In this article, we present a procedure based on genetic programming and multi-valued logic that enables the identification of high-order interactions of categorical variables such as SNPs. This method called GPAS cannot only be used for feature selection, but can also be employed for discrimination.<\/jats:p><jats:p>Results: In an application to the genotype data from the GENICA study, an association study concerned with sporadic breast cancer, GPAS is able to identify high-order interactions of SNPs leading to a considerably increased breast cancer risk for different subsets of patients that are not found by other feature selection methods. As an application to a subset of the HapMap data shows, GPAS is not restricted to association studies comprising several 10 SNPs, but can also be employed to analyze whole-genome data.<\/jats:p><jats:p>Availability: Software can be downloaded from http:\/\/ls2-www.cs.uni-dortmund.de\/~nunkesser\/#Software<\/jats:p><jats:p>Contact: \u00a0robin.nunkesser@uni-dortmund.de<\/jats:p>","DOI":"10.1093\/bioinformatics\/btm522","type":"journal-article","created":{"date-parts":[[2007,11,16]],"date-time":"2007-11-16T01:43:16Z","timestamp":1195177396000},"page":"3280-3288","source":"Crossref","is-referenced-by-count":47,"title":["Detecting high-order interactions of single nucleotide polymorphisms using genetic programming"],"prefix":"10.1093","volume":"23","author":[{"given":"Robin","family":"Nunkesser","sequence":"first","affiliation":[{"name":"1 Collaborative Research Center 475, 2Department of Computer Science and 3Department of Statistics, University of Dortmund, Dortmund, Germany"},{"name":"1 Collaborative Research Center 475, 2Department of Computer Science and 3Department of Statistics, University of Dortmund, Dortmund, Germany"}]},{"given":"Thorsten","family":"Bernholt","sequence":"additional","affiliation":[{"name":"1 Collaborative Research Center 475, 2Department of Computer Science and 3Department of Statistics, University of Dortmund, Dortmund, Germany"},{"name":"1 Collaborative Research Center 475, 2Department of Computer Science and 3Department of Statistics, University of Dortmund, Dortmund, Germany"}]},{"given":"Holger","family":"Schwender","sequence":"additional","affiliation":[{"name":"1 Collaborative Research Center 475, 2Department of Computer Science and 3Department of Statistics, University of Dortmund, Dortmund, Germany"},{"name":"1 Collaborative Research Center 475, 2Department of Computer Science and 3Department of Statistics, University of Dortmund, Dortmund, Germany"}]},{"given":"Katja","family":"Ickstadt","sequence":"additional","affiliation":[{"name":"1 Collaborative Research Center 475, 2Department of Computer Science and 3Department of Statistics, University of Dortmund, Dortmund, Germany"},{"name":"1 Collaborative Research Center 475, 2Department of Computer Science and 3Department of Statistics, University of Dortmund, Dortmund, Germany"}]},{"given":"Ingo","family":"Wegener","sequence":"additional","affiliation":[{"name":"1 Collaborative Research Center 475, 2Department of Computer Science and 3Department of Statistics, University of Dortmund, Dortmund, Germany"},{"name":"1 Collaborative Research Center 475, 2Department of Computer Science and 3Department of Statistics, University of Dortmund, Dortmund, Germany"}]}],"member":"286","published-online":{"date-parts":[[2007,11,15]]},"reference":[{"key":"2023041107274010900_","article-title":"BRLMM: an improved genotype calling method for the GeneChip Human Mapping 500k array set","volume-title":"Technical report","author":"Affymetrix","year":"2006"},{"key":"2023041107274010900_","volume-title":"Genetic Programming: an Introduction: on the Automatic Evolution of Computer Programs and Its Applications","author":"Banzhaf","year":"1998"},{"key":"2023041107274010900_","article-title":"Multiple testing for SNP-SNP interactions: a flexible asymptotic framework","volume-title":"Technical report, Sylvia Lawry Centre","author":"Boulesteix","year":"2007"},{"key":"2023041107274010900_","volume-title":"Classification and regression trees","author":"Breiman","year":"1984"},{"key":"2023041107274010900_","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/BF00058655","article-title":"Bagging predictors","volume":"26","author":"Breiman","year":"1996","journal-title":"Mach. Learn"},{"key":"2023041107274010900_","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1023\/A:1010933404324","article-title":"Random Forests","volume":"45","author":"Breiman","year":"2001","journal-title":"Mach. Learn"},{"key":"2023041107274010900_","volume-title":"Classification and Regression Trees","author":"Breiman","year":"1984"},{"key":"2023041107274010900_","volume-title":"Statistical Methods in Cancer Research: The Analysis of Case-control Studies","author":"Breslow","year":"1980"},{"key":"2023041107274010900_","volume-title":"Introduction to Algorithms","author":"Cormen","year":"2001","edition":"2nd"},{"key":"2023041107274010900_","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1086\/338759","article-title":"A perspective on epistasis: limits of models displaying no main effect","volume":"70","author":"Culverhouse","year":"2002","journal-title":"Am. J. Hum. Genet"},{"key":"2023041107274010900_","first-page":"1233","article-title":"Metabolic susceptibility genes as cancer risk factors: time for a reassessment?","volume":"10","author":"Garte","year":"2001","journal-title":"Cancer Epidemiol. Biomarkers Prev"},{"key":"2023041107274010900_","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1002\/ijc.21523","article-title":"Exploring SNP-SNP interactions and colon cancer risk using polymorphism interaction analysis","volume":"118","author":"Goodman","year":"2006","journal-title":"Int. J. Cancer"},{"key":"2023041107274010900_","article-title":"The challenge for genetic epidemiologists: how to analyze large numbers of SNPs in relation to complex diseases","volume":"7","author":"Heidema","year":"2006","journal-title":"Biomed. Genet"},{"key":"2023041107274010900_","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/nrg1155","article-title":"Mathematical multi-locus approaches to localizing complex human trait genes","volume":"4","author":"Hoh","year":"2003","journal-title":"Nat. Rev. Genet"},{"key":"2023041107274010900_","doi-asserted-by":"crossref","first-page":"2059","DOI":"10.1158\/1055-9965.2059.13.12","article-title":"ERCC2 genotypes and a corresponding haplotype are linked with breast cancer risk in a German population","volume":"13","author":"Justenhoven","year":"2004","journal-title":"Cancer Epidemiol. Biomarkers Prev"},{"key":"2023041107274010900_","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1002\/gepi.20042","article-title":"Identifying interacting SNPs using Monte Carlo logic regression","volume":"28","author":"Kooperberg","year":"2005","journal-title":"Genet. Epidemiol"},{"key":"2023041107274010900_","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1002\/gepi.2001.21.s1.s626","article-title":"Sequence analysis using logic regression","volume":"21","author":"Kooperberg","year":"2001","journal-title":"Genet. Epidemiol"},{"key":"2023041107274010900_","volume-title":"Genetic Programming \u2013 On the Programming of Computers by Means of Natural Selection","author":"Koza","year":"1993"},{"key":"2023041107274010900_","article-title":"Screening large-scale association study data: exploiting interactions using random forests","volume":"10","author":"Lunetta","year":"2004","journal-title":"BMC Genet"},{"key":"2023041107274010900_","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1038\/ng1537","article-title":"Genome-wide strategies for detecting multiple loci that influence complex diseases","volume":"37","author":"Marchini","year":"2005","journal-title":"Nat. Genet"},{"key":"2023041107274010900_","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1038\/nrc1476","article-title":"Association studies for finding cancer-susceptibility genetic variants","volume":"4","author":"Pharoah","year":"2004","journal-title":"Nat. Rev. Cancer"},{"key":"2023041107274010900_","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1086\/321276","article-title":"Multifactor-dimensionality reduction reveals high-order interactions among estrogen-metabolism genes in sporadic breast cancer","volume":"69","author":"Ritchie","year":"2001","journal-title":"Am. J. Hum. Genet"},{"key":"2023041107274010900_","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1198\/1061860032238","article-title":"Logic regression","volume":"12","author":"Ruczinski","year":"2003","journal-title":"J. Comput. Graph. Stat"},{"key":"2023041107274010900_","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.jmva.2004.02.010","article-title":"Exploring interactions in high-dimensional genomic data: an overview of logic regression, with applications","volume":"90","author":"Ruczinski","year":"2004","journal-title":"J. Mult. Anal"},{"key":"2023041107274010900_","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1007\/3-540-28084-7_42","article-title":"Modifying microarray analysis methods for categorical data \u2013 SAM and PAM for SNPs","volume-title":"Classification \u2013 The Ubiquitous Challenge","author":"Schwender","year":"2005"},{"key":"2023041107274010900_","volume-title":"Statistical analysis of genotype and gene expression data. Ph.D. Thesis","author":"Schwender","year":"2007"},{"key":"2023041107274010900_","article-title":"Identification of SNP interactions using logic regression","author":"Schwender","year":"2007","journal-title":"Biostatistics"},{"key":"2023041107274010900_","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1086\/379378","article-title":"A comparison of Bayesian methods for haplotype reconstruction","volume":"73","author":"Stephens","year":"2003","journal-title":"Am. J. Hum. Genet"},{"key":"2023041107274010900_","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1038\/nature02168","article-title":"The International HapMap Project","volume":"426","author":"The International HapMap Consortium","year":"2003","journal-title":"Nature"},{"key":"2023041107274010900_","doi-asserted-by":"crossref","first-page":"5116","DOI":"10.1073\/pnas.091062498","article-title":"Significance analysis of microarrays applied to the ionizing radiation response","volume":"98","author":"Tusher","year":"2001","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023041107274010900_","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1002\/gepi.2001.21.s1.s600","article-title":"Introduction: analysis of sequence data and population structure","volume":"21","author":"Witte","year":"2001","journal-title":"Genet. Epidemiol"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/23\/24\/3280\/49823932\/bioinformatics_23_24_3280.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/23\/24\/3280\/49823932\/bioinformatics_23_24_3280.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,14]],"date-time":"2023-05-14T19:17:32Z","timestamp":1684091852000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/23\/24\/3280\/264004"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,11,15]]},"references-count":31,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2007,12,15]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btm522","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2007,12,15]]},"published":{"date-parts":[[2007,11,15]]}}}