Quantitative comparison of microarray experiments with published leukemia related gene expression signatures

被引:42
作者
Klein, Hans-Ulrich [1 ]
Ruckert, Christian [1 ]
Kohlmann, Alexander [2 ]
Bullinger, Lars [3 ]
Thiede, Christian [4 ]
Haferlach, Torsten [2 ]
Dugas, Martin [1 ]
机构
[1] Univ Munster, Dept Med Informat & Biomath, D-48149 Munster, Germany
[2] Munich Leukemia Lab, D-81377 Munich, Germany
[3] Univ Ulm, D-89081 Ulm, Germany
[4] Univ Hosp Dresden, Med Clin 1, D-01307 Dresden, Germany
来源
BMC BIOINFORMATICS | 2009年 / 10卷
关键词
ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; SET ENRICHMENT; TESTING ASSOCIATION; PREDICTION; DISCOVERY; CANCER; REPRODUCIBILITY; BIOINFORMATICS; CLASSIFICATION;
D O I
10.1186/1471-2105-10-422
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Background: Multiple gene expression signatures derived from microarray experiments have been published in the field of leukemia research. A comparison of these signatures with results from new experiments is useful for verification as well as for interpretation of the results obtained. Currently, the percentage of overlapping genes is frequently used to compare published gene signatures against a signature derived from a new experiment. However, it has been shown that the percentage of overlapping genes is of limited use for comparing two experiments due to the variability of gene signatures caused by different array platforms or assay-specific influencing parameters. Here, we present a robust approach for a systematic and quantitative comparison of published gene expression signatures with an exemplary query dataset. Results: A database storing 138 leukemia-related published gene signatures was designed. Each gene signature was manually annotated with terms according to a leukemia-specific taxonomy. Two analysis steps are implemented to compare a new microarray dataset with the results from previous experiments stored and curated in the database. First, the global test method is applied to assess gene signatures and to constitute a ranking among them. In a subsequent analysis step, the focus is shifted from single gene signatures to chromosomal aberrations or molecular mutations as modeled in the taxonomy. Potentially interesting disease characteristics are detected based on the ranking of gene signatures associated with these aberrations stored in the database. Two example analyses are presented. An implementation of the approach is freely available as web-based application. Conclusions: The presented approach helps researchers to systematically integrate the knowledge derived from numerous microarray experiments into the analysis of a new dataset. By means of example leukemia datasets we demonstrate that this approach detects related experiments as well as related molecular mutations and may help to interpret new microarray data.
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页数:11
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