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We address the question of which of several normalization methods is optimal prior to computing the correlation of the expression profiles between every pair of genes.<\/jats:p><jats:p>Results: We use gene expression data from five experiments with a total of 78 hybridizations and 23 diverse conditions. Nine methods of data normalization are explored based on all possible combinations of normalization techniques according to between and within gene and experiment variation. We compare the resulting empirical distribution of gene \u00d7 gene correlations with the expectations and apply cross-validation to test the performance of each method in predicting accurate functional annotation. We conclude that normalization methods based on mixed-model equations are optimal.<\/jats:p><jats:p>Contact: \u00a0tony.reverter-gomez@csiro.au<\/jats:p>","DOI":"10.1093\/bioinformatics\/bti124","type":"journal-article","created":{"date-parts":[[2004,11,26]],"date-time":"2004-11-26T01:13:24Z","timestamp":1101431604000},"page":"1112-1120","source":"Crossref","is-referenced-by-count":56,"title":["Validation of alternative methods of data normalization in gene co-expression studies"],"prefix":"10.1093","volume":"21","author":[{"given":"Antonio","family":"Reverter","sequence":"first","affiliation":[{"name":"Bioinformatics Group, CSIRO Livestock Industries, Queensland Bioscience Precinct St Lucia, QLD 4067, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wes","family":"Barris","sequence":"additional","affiliation":[{"name":"Bioinformatics Group, CSIRO Livestock Industries, Queensland Bioscience Precinct St Lucia, QLD 4067, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sean","family":"McWilliam","sequence":"additional","affiliation":[{"name":"Bioinformatics Group, CSIRO Livestock Industries, Queensland Bioscience Precinct St Lucia, QLD 4067, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keren A.","family":"Byrne","sequence":"additional","affiliation":[{"name":"Bioinformatics Group, CSIRO Livestock Industries, Queensland Bioscience Precinct St Lucia, QLD 4067, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong H.","family":"Wang","sequence":"additional","affiliation":[{"name":"Bioinformatics Group, CSIRO Livestock Industries, Queensland Bioscience Precinct St Lucia, QLD 4067, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siok H.","family":"Tan","sequence":"additional","affiliation":[{"name":"Bioinformatics Group, CSIRO Livestock Industries, Queensland Bioscience Precinct St Lucia, QLD 4067, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nick","family":"Hudson","sequence":"additional","affiliation":[{"name":"Bioinformatics Group, CSIRO Livestock Industries, Queensland Bioscience Precinct St Lucia, QLD 4067, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian P.","family":"Dalrymple","sequence":"additional","affiliation":[{"name":"Bioinformatics Group, CSIRO Livestock Industries, Queensland Bioscience Precinct St Lucia, QLD 4067, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2004,11,25]]},"reference":[{"key":"2023013107281860600_B1","doi-asserted-by":"crossref","unstructured":"Baird, D., Johnston, P., Wilson, T. 2004Normalization of microarray data using a spatial mixed model analysis which includes splines. 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