{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T21:00:54Z","timestamp":1767992454301,"version":"3.49.0"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Bioinformatics"],"published-print":{"date-parts":[[2007,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>With the explosion in data generated using microarray technology by different investigators working on similar experiments, it is of interest to combine results across multiple studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In this article, we describe a general probabilistic framework for combining high-throughput genomic data from several related microarray experiments using mixture models. A key feature of the model is the use of latent variables that represent quantities that can be combined across diverse platforms. We consider two methods for estimation of an index termed the probability of expression (POE). The first, reported in previous work by the authors, involves Markov Chain Monte Carlo (MCMC) techniques. The second method is a faster algorithm based on the expectation-maximization (EM) algorithm. The methods are illustrated with application to a meta-analysis of datasets for metastatic cancer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The statistical methods described in the paper are available as an R package, metaArray 1.8.1, which is at Bioconductor, whose URL is<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.bioconductor.org\/\" ext-link-type=\"uri\">http:\/\/www.bioconductor.org\/<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1471-2105-8-364","type":"journal-article","created":{"date-parts":[[2007,9,28]],"date-time":"2007-09-28T06:13:13Z","timestamp":1190959993000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["A Latent Variable Approach for Meta-Analysis of Gene Expression Data from Multiple Microarray Experiments"],"prefix":"10.1186","volume":"8","author":[{"given":"Hyungwon","family":"Choi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronglai","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arul M","family":"Chinnaiyan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debashis","family":"Ghosh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2007,9,27]]},"reference":[{"key":"1736_CR1","volume-title":"Statistical methods for meta-analysis","author":"L Hedges","year":"1985","unstructured":"Hedges L, Olkin I: Statistical methods for meta-analysis. New York: Academic Press; 1985."},{"key":"1736_CR2","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1002\/(SICI)1097-0258(19990215)18:3<321::AID-SIM28>3.0.CO;2-P","volume":"18","author":"SLT Normand","year":"1999","unstructured":"Normand SLT: Meta-analysis: Formulating, Evaluating, Combining, and Reporting. Statistics in Medicine 1999, 18: 321\u2013359. 10.1002\/(SICI)1097-0258(19990215)18:3<321::AID-SIM28>3.0.CO;2-P","journal-title":"Statistics in Medicine"},{"key":"1736_CR3","first-page":"4427","volume":"62","author":"D Rhodes","year":"2002","unstructured":"Rhodes D, Barrette TR, Rubin MA, Ghosh D, Chinnaiyan AM: Meta-Analysis of Microarrays: Interstudy Validation of Gene Expression Profiles Reveals Pathway Dysregulation in Prostate Cancer. Cancer Research 2002, 62: 4427\u201333.","journal-title":"Cancer Research"},{"key":"1736_CR4","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1111\/1467-9868.00346","volume":"64","author":"JD Storey","year":"2002","unstructured":"Storey JD: A direct approach to false discovery rates. J R Stat Soc B 2002, 64: 479\u201398. 10.1111\/1467-9868.00346","journal-title":"J R Stat Soc B"},{"key":"1736_CR5","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1093\/bioinformatics\/btg1010","volume":"19","author":"JK Choi","year":"2003","unstructured":"Choi JK, Yu U, Kim S, Yoo OJ: Combining multiple microarray studies and modeling interstudy variation. Bioinformatics 2003, 19: 184\u2013190. 10.1093\/bioinformatics\/btg1010","journal-title":"Bioinformatics"},{"key":"1736_CR6","doi-asserted-by":"publisher","first-page":"3166","DOI":"10.1093\/bioinformatics\/bth381","volume":"20","author":"J Wang","year":"2004","unstructured":"Wang J, Coombes K, Highsmith W, Keating M, Abruzzo L: Differences in gene expression between B-cell chronic lymphocytic leukemia and normal B cells: a meta-analysis of three microarray studies. Bioinformatics 2004, 20: 3166\u201378. 10.1093\/bioinformatics\/bth381","journal-title":"Bioinformatics"},{"key":"1736_CR7","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1111\/1467-9868.00358","volume":"64","author":"G Parmigiani","year":"2002","unstructured":"Parmigiani G, Garrett ES, Anbazhagan R, Gabrielson E: A statistical framework for expression-based molecular classification in cancer. J R Stat Soc B 2002, 64: 717\u201336. 10.1111\/1467-9868.00358","journal-title":"J R Stat Soc B"},{"key":"1736_CR8","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1186\/1471-2164-5-94","volume":"5","author":"R Shen","year":"2004","unstructured":"Shen R, Ghosh D, Chinnaiyan AM: Prognostic meta-signature of breast cancer developed by two-stage mixture modeling of microarray data. BMC Genomics 2004, 5: 94. 10.1186\/1471-2164-5-94","journal-title":"BMC Genomics"},{"key":"1736_CR9","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","volume":"57","author":"Y Benjamini","year":"1995","unstructured":"Benjamini Y, Hochberg Y: Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing. J R Statist Soc Ser B 1995, 57: 289\u201330.","journal-title":"J R Statist Soc Ser B"},{"key":"1736_CR10","first-page":"4499","volume":"62","author":"E LaTulippe","year":"2002","unstructured":"LaTulippe E, Satagopan J, Smith A, Scher H, Scardino P, Reuter V, Gerald WL: Comprehensive gene expression analysis of prostate cancer reveals distinct transcriptional programs associated with metastatic disease. Cancer Res 2002, 62: 4499\u2013506.","journal-title":"Cancer Res"},{"key":"1736_CR11","doi-asserted-by":"publisher","first-page":"13784","DOI":"10.1073\/pnas.241500798","volume":"98","author":"M Garber","year":"2001","unstructured":"Garber M, Troyanskaya O, Schluens K, Petersen S, Thaesler Z, Pacyna-Gengelbach M, van de Rijn M, Rosen G, Perou C, Whyte R, Altman R, Brown P, Botstein D, Petersen I: Diversity of gene expression in adenocarcinoma of the lung. Proc Natl Acad Sci USA 2001, 98: 13784\u201313789. 10.1073\/pnas.241500798","journal-title":"Proc Natl Acad Sci USA"},{"key":"1736_CR12","doi-asserted-by":"publisher","first-page":"1929","DOI":"10.1091\/mbc.02-02-0023.","volume":"13","author":"X Chen","year":"2002","unstructured":"Chen X, Cheung ST, So S, Fan ST, Barry C, Higgins J, Lai KM, Ji J, Dudoit S, Ng IO, Van De Rijn M, Botstein D, Brown PO: Gene expression patterns in human liver cancers. Mol Biol Cell 2002, 13: 1929\u20131939. 10.1091\/mbc.02-02-0023.","journal-title":"Mol Biol Cell"},{"key":"1736_CR13","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1186\/1471-2105-7-247","volume":"7","author":"EM Conlon","year":"2006","unstructured":"Conlon EM, Song JJ, Liu JS: Bayesian models for pooling microarray studies with multiple sources of replications. BMC Bioinformatics 2006, 7: 247. 10.1186\/1471-2105-7-247","journal-title":"BMC Bioinformatics"},{"key":"1736_CR14","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1038\/415530a","volume":"415","author":"LJ vant Veer","year":"2002","unstructured":"vant Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, Peterse HL, van der Kooy K, Marton MJ, Witteveen AT, Schreiber GJ, Kerkhoven RM, Roberts C, Linsley PS, Bernards R, Friend S: Gene expression profiling predicts clinical outcome of breast cancer. Nature 2002, 415: 530\u20136. 10.1038\/415530a","journal-title":"Nature"},{"key":"1736_CR15","doi-asserted-by":"publisher","first-page":"9309","DOI":"10.1073\/pnas.0401994101","volume":"101","author":"D Rhodes","year":"2004","unstructured":"Rhodes D, Yu J, Shanker K, Deshpande N, Varambally R, Ghosh D, Barrette T, Pandey A, Chinnaiyan A: Large-scale meta-analysis of cancer microarray data identifies common transcriptional profiles of neoplastic transformation and progression. Proc Natl Acad Sci USA 2004, 101: 9309\u201314. 10.1073\/pnas.0401994101","journal-title":"Proc Natl Acad Sci USA"},{"key":"1736_CR16","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1093\/nar\/gkg014","volume":"31","author":"M Diehn","year":"2003","unstructured":"Diehn M, Sherlock G, Binkley G, Jin H, Matese JC, Hernandez-Boussard T, Rees CA, Cherry JM, Botstein D, Brown PO, Alizadeh AA: SOURCE: a unified genomic resource of functional annotations, ontologies, and gene expression data. Nucleic Acids Research 2003, 31: 219\u2013223. 10.1093\/nar\/gkg014","journal-title":"Nucleic Acids Research"},{"key":"1736_CR17","unstructured":"The BUGS Project[http:\/\/www.mrc-bsu.cam.ac.uk\/bugs]"},{"key":"1736_CR18","unstructured":"DAVID 2007 Functional Annotation Bioinformatics Microarray Analysis[http:\/\/niaid.abcc.ncifcrf.gov\/]"},{"key":"1736_CR19","doi-asserted-by":"publisher","first-page":"1582","DOI":"10.1172\/JCI27236","volume":"116","author":"P Kaposi-Novak","year":"2006","unstructured":"Kaposi-Novak P, Lee JS, Gomez-Quiroz L, Coulouarn C, Factor VM, Thorgeirsson SS: Met-regulated expression signature defines asubset of human hepatocellular carcinomas with poor prognosis and aggresive phenotype. Journal of Clinical Investigation 2006, 116: 1582\u20131595. 10.1172\/JCI27236","journal-title":"Journal of Clinical Investigation"},{"key":"1736_CR20","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1159\/000086627","volume":"69","author":"N Oue","year":"2005","unstructured":"Oue N, Aung PP, Mitani Y, Kuniyasu H, Nakayama H, Yasui W: Genes involved in invasion and metastasis of gastric cancer identified by array-based hybridization and serial analysis of gene expression. Oncology 2005, 69: 17\u201322. 10.1159\/000086627","journal-title":"Oncology"},{"key":"1736_CR21","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1158\/0008-5472.CAN-06-1514","volume":"67","author":"M Grade","year":"2007","unstructured":"Grade M, Hormann P, Becker S, Hummon AB, Wangsa D, Varma S, Simon R, Liersch T, Becker H, Difilippantonio MJ, Ghadimi M, Ried T: Gene expression profiling reveals a massive aneuploidy-dependent transcriptional deregulation and distinct differences between lymph node-negative and lymph node-positive colon carcinomas. Cancer Research 2007, 67: 41\u201356. 10.1158\/0008-5472.CAN-06-1514","journal-title":"Cancer Research"},{"key":"1736_CR22","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1111\/j.2517-6161.1972.tb00899.x","volume":"34","author":"DR Cox","year":"1972","unstructured":"Cox DR: Regression models and life tables (with discussion). J R Statist Soc Ser B 1972, 34: 187\u2013220.","journal-title":"J R Statist Soc Ser B"},{"key":"1736_CR23","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1002\/(SICI)1097-0258(19960229)15:4<361::AID-SIM168>3.0.CO;2-4","volume":"15","author":"FE Harrell","year":"1996","unstructured":"Harrell FE, Lee KL, Mark DB: Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Stat Med 1996, 15: 361\u2013387. Publisher Full Text 10.1002\/(SICI)1097-0258(19960229)15:4<361::AID-SIM168>3.0.CO;2-4","journal-title":"Stat Med"},{"key":"1736_CR24","doi-asserted-by":"publisher","first-page":"R82","DOI":"10.1186\/gb-2003-4-12-r82","volume":"4","author":"J Lee","year":"2003","unstructured":"Lee J, Bussey K, Gwadry F, Reinhold W, Riddick G, Pelletier S, Nishizuka S, Szakacs G, Annereau J, Shankavaram U, Lababidi S, Smith L, Gottesman M, Weinstein J: Comparing cDNA and oligonucleotide array data: concordance of gene expression across platforms for the NCI-60 cancer cells. Genome Biology 2003, 4: R82. 10.1186\/gb-2003-4-12-r82","journal-title":"Genome Biology"},{"key":"1736_CR25","doi-asserted-by":"publisher","first-page":"2922","DOI":"10.1158\/1078-0432.CCR-03-0490","volume":"10","author":"G Parmigiani","year":"2004","unstructured":"Parmigiani G, Garrett-Meyer ES, Anbazhagan R, Gabrielson E: A cross-study comparison of gene expression studies for the molecular classification of lung cancer. Clin Cancer Res 2004, 10: 2922\u20137. 10.1158\/1078-0432.CCR-03-0490","journal-title":"Clin Cancer Res"},{"key":"1736_CR26","unstructured":"metaArray[http:\/\/www.bioconductor.org\/packages\/2.0\/bioc\/html\/metaArray.html]"},{"key":"1736_CR27","doi-asserted-by":"publisher","first-page":"el5","DOI":"10.1093\/nar\/30.2.e5","volume":"30","author":"YH Yang","year":"2002","unstructured":"Yang YH, Dudoit S, Luu P, Lin DM, Peng V, Ngai J, Speed TP: Normalization for cDNA microarray data: a robust composite method addressing single and multiple slide systematic variation. Nucleic Acids Research 2002, 30: el5.","journal-title":"Nucleic Acids Research"},{"key":"1736_CR28","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1093\/biostatistics\/4.2.249","volume":"4","author":"RA Irizarry","year":"2003","unstructured":"Irizarry RA, Hobbs B, Collin F, Beazer-Barclay YD, Antonellis KJ, Scherf U, Speed TP: Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics 2003, 4: 249\u2013264. 10.1093\/biostatistics\/4.2.249","journal-title":"Biostatistics"},{"key":"1736_CR29","doi-asserted-by":"publisher","first-page":"5116","DOI":"10.1073\/pnas.091062498","volume":"98","author":"VG Tusher","year":"2001","unstructured":"Tusher VG, Tibshirani R, Chu G: Significance analysis of microarrays applied to ionizing radiation response. Proc Natl Acad Sci 2001, 98: 5116\u201321. 10.1073\/pnas.091062498","journal-title":"Proc Natl Acad Sci"},{"key":"1736_CR30","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1186\/1471-2105-6-173","volume":"6","author":"N Dean","year":"2005","unstructured":"Dean N, Raftery AE: Normal uniform mixture differential gene expression detection for cDNA microarrays. BMC Bioinformatics 2005, 6: 173. 10.1186\/1471-2105-6-173","journal-title":"BMC Bioinformatics"},{"key":"1736_CR31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.2517-6161.1977.tb01600.x","volume":"39","author":"AP Dempster","year":"1977","unstructured":"Dempster AP, Laird NM, Rubin DB: Maximum Likelihood from Incomplete Data Via the EM Algorithm (C\/R: P22\u201337). Journal of the Royal Statistical Society, Series B: Methodological 1977, 39: 1\u201322.","journal-title":"Journal of the Royal Statistical Society, Series B: Methodological"},{"key":"1736_CR32","doi-asserted-by":"crossref","first-page":"S22","DOI":"10.2144\/mar03scharpf","volume":"34","author":"R Scharpf","year":"2003","unstructured":"Scharpf R, Garrett ES, Hu J, Parmigiani G: Statistical modeling and visualization of molecular profiles in cancer. BioTechniques 2003, 34: S22-S29.","journal-title":"BioTechniques"},{"key":"1736_CR33","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1186\/1471-2105-5-110","volume":"5","author":"J Lyons-Weiler","year":"2004","unstructured":"Lyons-Weiler J, Patel S, Becich MJ, Godfrey T: Tests for finding complex patterns of differential expression in cancers: towards individualized medicine. BMC Bioinformatics 2004, 5: 110. 10.1186\/1471-2105-5-110","journal-title":"BMC Bioinformatics"},{"key":"1736_CR34","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1093\/biostatistics\/5.2.155","volume":"5","author":"MA Newton","year":"2004","unstructured":"Newton MA, Noueiry A, Sarkar D, Ahlquist P: Detecting differential gene expression with a semiparametric hierarchical mixture method. Biostatistics 2004, 5: 155\u2013176. 10.1093\/biostatistics\/5.2.155","journal-title":"Biostatistics"},{"key":"1736_CR35","doi-asserted-by":"publisher","first-page":"3899","DOI":"10.1002\/sim.1548","volume":"22","author":"CM Kendziorski","year":"2003","unstructured":"Kendziorski CM, Newton MA, Lan H, Gould MN: On parametric empirical Bayes methods for comparing multiple groups using replicated gene expression profiles. Stat Med 2003, 22: 3899\u20133914. 10.1002\/sim.1548","journal-title":"Stat Med"},{"key":"1736_CR36","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1016\/0197-2456(93)90225-3","volume":"14","author":"JW Tukey","year":"1993","unstructured":"Tukey JW: Tightening the Clinical Trial. Controlled Clinical Trials 1993, 14: 266\u2013285. 10.1016\/0197-2456(93)90225-3","journal-title":"Controlled Clinical Trials"}],"container-title":["BMC Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2105-8-364.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T07:57:53Z","timestamp":1737446273000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/1471-2105-8-364"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,9,27]]},"references-count":36,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2007,12]]}},"alternative-id":["1736"],"URL":"https:\/\/doi.org\/10.1186\/1471-2105-8-364","relation":{},"ISSN":["1471-2105"],"issn-type":[{"value":"1471-2105","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,9,27]]},"assertion":[{"value":"26 February 2007","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 September 2007","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 September 2007","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"364"}}