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pmid:21092329
Validation and characterization of DNA microarray gene expression data distribution and associated moments.
Reuben Thomas · Luis de la Torre · Xiaoqing Chang · Sanjay Mehrotra
BMC bioinformatics · 2010 doi:10.1186/1471-2105-11-576
Paper
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Experiment
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Data
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Analysis
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Execution
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Complete file
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This knowledge is then further used in order to generate molecular mechanistic hypotheses for an organism when it is exposed to different conditions. Several different methods have been proposed to analyze these data under different distributional assumptions on gene expression. However, the empirical validation of these assumptions is lacking.\nRESULTS: Best fit hypotheses tests, moment-ratio diagrams and relationships between the different moments of the distribution of the gene expression was used to characterize the observed distributions. The data are obtained from the publicly available gene expression database, Gene Expression Omnibus (GEO) to characterize the empirical distributions of gene expressions obtained under varying experimental situations each of which providing relatively large number of samples for hypothesis testing. All data were obtained from either of two microarray platforms--the commercial Affymetrix mouse 430.2 platform and a non-commercial Rosetta/Merck one. The data from each platform were preprocessed in the same manner.\nCONCLUSIONS: The null hypotheses for goodness of fit for all considered univariate theoretical probability distributions (including the Normal distribution) are rejected for more than 50% of probe sets on the Affymetrix microarray platform at a 95% confidence level, suggesting that under the tested conditions a priori assumption of any of these distributions across all probe sets is not valid. The pattern of null hypotheses rejection was different for the data from Rosetta/Merck platform with only around 20% of the probe sets failing the logistic distribution goodness-of-fit test. We find that there are statistically significant (at 95% confidence level based on the F-test for the fitted linear model) relationships between the mean and the logarithm of the coefficient of variation of the distributions of the logarithm of gene expressions. An additional novel statistically significant quadratic relationship between the skewness and kurtosis is identified. Data from both microarray platforms fail to identify with any one of the chosen theoretical probability distributions from an analysis of the l-moment ratio diagram.", "claims": [{"id": "claim-method", "statement": "In this manuscript the results for the AD are provided while those for the KS tests are provided in the Additional material.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:21092329", "locator": "sections[5] \"Testing Distributional Assumptions\" paragraph 2", "quote": "In this manuscript the results for the AD are provided while those for the KS tests are provided in the Additional material."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The microarray samples used in the analyses in this manuscript were based in part on six separate data sets (see Table 1 and Additional files 1, 2, 3, 4, Table S8, Table S3, Table S1 and Table S2 for better detail of the data in Table 1) obtained from the GEO database [30].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:21092329", "locator": "sections[3] \"Data sets used in the analysis\" paragraph 2", "quote": "The microarray samples used in the analyses in this manuscript were based in part on six separate data sets (see Table 1 and Additional files 1, 2, 3, 4, Table S8, Table S3, Table S1 and Table S2 for better detail of the data in Table 1) obtained from the GEO database [30]."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:21092329"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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