{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T19:43:53Z","timestamp":1760298233278,"version":"3.37.3"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2016,10,2]],"date-time":"2016-10-02T00:00:00Z","timestamp":1475366400000},"content-version":"vor","delay-in-days":2397,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/2.0\/uk\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Motivation: Microarrays are being increasingly used in cancer research to better characterize and classify tumors by selecting marker genes. However, as very few of these genes have been validated as predictive biomarkers so far, it is mostly conventional clinical and pathological factors that are being used as prognostic indicators of clinical course. Combining clinical data with gene expression data may add valuable information, but it is a challenging task due to their categorical versus continuous characteristics. We have further developed the mixture of experts (ME) methodology, a promising approach to tackle complex non-linear problems. Several variants are proposed in integrative ME as well as the inclusion of various gene selection methods to select a hybrid signature.<\/jats:p><jats:p>Results: We show on three cancer studies that prediction accuracy can be improved when combining both types of variables. Furthermore, the selected genes were found to be of high relevance and can be considered as potential biomarkers for the prognostic selection of cancer therapy.<\/jats:p><jats:p>Availability: Integrative ME is implemented in the R package integrativeME (http:\/\/cran.r-project.org\/).<\/jats:p><jats:p>Contact: \u00a0k.lecao@uq.edu.au<\/jats:p><jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btq107","type":"journal-article","created":{"date-parts":[[2010,3,12]],"date-time":"2010-03-12T01:50:37Z","timestamp":1268358637000},"page":"1192-1198","source":"Crossref","is-referenced-by-count":22,"title":["Integrative mixture of experts to combine clinical factors and gene markers"],"prefix":"10.1093","volume":"26","author":[{"given":"Kim-Anh","family":"L\u00ea Cao","sequence":"first","affiliation":[{"name":"1 ARC Centre of Excellence in Bioinformatics, Institute for Molecular Bioscience, University of Queensland, 4072 St Lucia, QLD, Australia, 2 INRA 1235, INSERM U870, INSA-Lyon, R\u00e9gulations M\u00e9taboliques Nutrition et Diab\u00e8tes, Universit\u00e9 de Lyon, Oullins, F-69600, France and 3 Department of Mathematics and Institute for Molecular Bioscience, University of Queensland, 4072 St Lucia, QLD, Australia"}]},{"given":"Emmanuelle","family":"Meugnier","sequence":"additional","affiliation":[{"name":"1 ARC Centre of Excellence in Bioinformatics, Institute for Molecular Bioscience, University of Queensland, 4072 St Lucia, QLD, Australia, 2 INRA 1235, INSERM U870, INSA-Lyon, R\u00e9gulations M\u00e9taboliques Nutrition et Diab\u00e8tes, Universit\u00e9 de Lyon, Oullins, F-69600, France and 3 Department of Mathematics and Institute for Molecular Bioscience, University of Queensland, 4072 St Lucia, QLD, Australia"}]},{"given":"Geoffrey J.","family":"McLachlan","sequence":"additional","affiliation":[{"name":"1 ARC Centre of Excellence in Bioinformatics, Institute for Molecular Bioscience, University of Queensland, 4072 St Lucia, QLD, Australia, 2 INRA 1235, INSERM U870, INSA-Lyon, R\u00e9gulations M\u00e9taboliques Nutrition et Diab\u00e8tes, Universit\u00e9 de Lyon, Oullins, F-69600, France and 3 Department of Mathematics and Institute for Molecular Bioscience, University of Queensland, 4072 St Lucia, QLD, Australia"}]}],"member":"286","published-online":{"date-parts":[[2010,3,11]]},"reference":[{"key":"2023012508165406000_B1","doi-asserted-by":"crossref","first-page":"1698","DOI":"10.1093\/bioinformatics\/btn262","article-title":"Microarray-based classification and clinical predictors: on combined classifiers and additional predictive value","volume":"24","author":"Boulesteix","year":"2008","journal-title":"Bioinformatics"},{"key":"2023012508165406000_B2","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":"2023012508165406000_B3","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1016\/S0893-6080(99)00043-X","article-title":"Improved learning algorithms for mixture of experts in multiclass classification","volume":"12","author":"Chen","year":"1999","journal-title":"Neural Netw."},{"key":"2023012508165406000_B4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.2517-6161.1977.tb01600.x","article-title":"Maximum likelihood from incomplete data via the EM algorithm","volume":"1","author":"Dempster","year":"1977","journal-title":"J. R Stat. Soc. Ser. B"},{"key":"2023012508165406000_B5","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.jmva.2004.02.012","article-title":"Finding predictive gene groups from microarray data","volume":"90","author":"Dettling","year":"2004","journal-title":"J. Multivariate Anal."},{"key":"2023012508165406000_B6","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1111\/j.1365-2141.2007.06763.x","article-title":"Genetic alterations determine chemotherapy resistance in childhood T-ALL: modelling in stage-specific cell lines and correlation with diagnostic patient samples","volume":"139","author":"Estes","year":"2007","journal-title":"Br. J. 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