Dataset Information

Mining published lists of cancer related microarray experiments: identification of a gene expression signature having a critical role in cell-cycle control.

ABSTRACT: BACKGROUND: Routine application of gene expression microarray technology is rapidly producing large amounts of data that necessitate new approaches of analysis. The analysis of a specific microarray experiment profits enormously from cross-comparing to other experiments. This process is generally performed by numerical meta-analysis of published data where the researcher chooses the datasets to be analyzed based on assumptions about the biological relations of published datasets to his own data, thus severely limiting the possibility of finding surprising connections. Here we propose using a repository of published gene lists for the identification of interesting datasets to be subjected to more detailed numerical analysis. RESULTS: We have compiled lists of genes that have been reported as differentially regulated in cancer related microarray studies. We searched these gene lists for statistically significant overlaps with lists of genes regulated by the tumor suppressors p16 and pRB. We identified a highly significant overlap of p16 and pRB target genes with genes regulated by the EWS/FLI fusion protein. Detailed numerical analysis of these data identified two sets of genes with clearly distinct roles in the G1/S and the G2/M phases of the cell cycle, as measured by enrichment of Gene Ontology categories. CONCLUSION: We show that mining of published gene lists in the absence of numerical detail about gene expression levels constitutes a fast, easy to perform, widely applicable, and unbiased route towards the identification of biologically related gene expression microarray datasets.

SUBMITTER: Finocchiaro G

PROVIDER: S-EPMC1866394 | biostudies-literature | 2005

REPOSITORIES: biostudies-literature

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Mining published lists of cancer related microarray experiments: identification of a gene expression signature having a critical role in cell-cycle control.

Finocchiaro Giacomo G Mancuso Francesco F Muller Heiko H

BMC bioinformatics 20051201

<h4>Background</h4>Routine application of gene expression microarray technology is rapidly producing large amounts of data that necessitate new approaches of analysis. The analysis of a specific microarray experiment profits enormously from cross-comparing to other experiments. This process is generally performed by numerical meta-analysis of published data where the researcher chooses the datasets to be analyzed based on assumptions about the biological relations of published datasets to his ow ...[more]

PMID: 16351740

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Project description:BackgroundMultiple 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.ResultsA 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.ConclusionsThe 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.

Project description:BACKGROUND: In the postgenome era, a prediction of response to treatment could lead to better dose selection for patients in radiotherapy. To identify a radiosensitive gene signature and elucidate related signaling pathways, four different microarray experiments were reanalyzed before radiotherapy. RESULTS: Radiosensitivity profiling data using clonogenic assay and gene expression profiling data from four published microarray platforms applied to NCI-60 cancer cell panel were used. The survival fraction at 2?Gy (SF2, range from 0 to 1) was calculated as a measure of radiosensitivity and a linear regression model was applied to identify genes or a gene set with a correlation between expression and radiosensitivity (SF2). Radiosensitivity signature genes were identified using significant analysis of microarrays (SAM) and gene set analysis was performed using a global test using linear regression model. Using the radiation-related signaling pathway and identified genes, a genetic network was generated. According to SAM, 31 genes were identified as common to all the microarray platforms and therefore a common radiosensitivity signature. In gene set analysis, functions in the cell cycle, DNA replication, and cell junction, including adherence and gap junctions were related to radiosensitivity. The integrin, VEGF, MAPK, p53, JAK-STAT and Wnt signaling pathways were overrepresented in radiosensitivity. Significant genes including ACTN1, CCND1, HCLS1, ITGB5, PFN2, PTPRC, RAB13, and WAS, which are adhesion-related molecules that were identified by both SAM and gene set analysis, and showed interaction in the genetic network with the integrin signaling pathway. CONCLUSIONS: Integration of four different microarray experiments and gene selection using gene set analysis discovered possible target genes and pathways relevant to radiosensitivity. Our results suggested that the identified genes are candidates for radiosensitivity biomarkers and that integrin signaling via adhesion molecules could be a target for radiosensitization.

Project description:BackgroundThis paper describes the results of a Gene Ontology (GO) term enrichment analysis of chicken microarray data using the Bioconductor packages. By checking the enriched GO terms in three contrasts, MM8-PM8, MM8-MA8, and MM8-MM24, of the provided microarray data during this workshop, this analysis aimed to investigate the host reactions in chickens occurring shortly after a secondary challenge with either a homologous or heterologous species of Eimeria. The results of GO enrichment analysis using GO terms annotated to chicken genes and GO terms annotated to chicken-human orthologous genes were also compared. Furthermore, a locally adaptive statistical procedure (LAP) was performed to test differentially expressed chromosomal regions, rather than individual genes, in the chicken genome after Eimeria challenge.ResultsGO enrichment analysis identified significant (raw p-value < 0.05) GO terms for all three contrasts included in the analysis. Some of the GO terms linked to, generally, primary immune responses or secondary immune responses indicating the GO enrichment analysis is a useful approach to analyze microarray data. The comparisons of GO enrichment results using chicken gene information and chicken-human orthologous gene information showed more refined GO terms related to immune responses when using chicken-human orthologous gene information, this suggests that using chicken-human orthologous gene information has higher power to detect significant GO terms with more refined functionality. Furthermore, three chromosome regions were identified to be significantly up-regulated in contrast MM8-PM8 (q-value < 0.01).ConclusionOverall, this paper describes a practical approach to analyze microarray data in farm animals where the genome information is still incomplete. For farm animals, such as chicken, with currently limited gene annotation, borrowing gene annotation information from orthologous genes in well-annotated species, such as human, will help improve the pathway analysis results substantially. Furthermore, LAP analysis approach is a relatively new and very useful way to be applied in microarray analysis.

Dataset Information

Mining published lists of cancer related microarray experiments: identification of a gene expression signature having a critical role in cell-cycle control.

Publications

Mining published lists of cancer related microarray experiments: identification of a gene expression signature having a critical role in cell-cycle control.

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