Abstract
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. 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. 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.
MeSH Terms
Cell Cycle
Computational Biology/methods
Cyclin-Dependent Kinase Inhibitor p16/biosynthesis
Data Interpretation, Statistical
Databases, Factual
Databases, Genetic
Gene Expression Profiling/methods
Gene Expression Regulation, Neoplastic
Humans
Information Storage and Retrieval
Models, Statistical
Models, Theoretical
Neoplasms/metabolism
Oligonucleotide Array Sequence Analysis/methods
Oncogene Proteins, Fusion/biosynthesis
Proto-Oncogene Protein c-fli-1
RNA-Binding Protein EWS
Research Design
Retinoblastoma Protein/biosynthesis
Software
Statistics as Topic
Transcription Factors/biosynthesis
Chemicals
Cyclin-Dependent Kinase Inhibitor p16
EWS-FLI fusion protein
Oncogene Proteins, Fusion
Proto-Oncogene Protein c-fli-1
RNA-Binding Protein EWS
Retinoblastoma Protein
Transcription Factors
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Finocchiaro Giacomo
European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy.
[email protected]
Mancuso Francesco
Muller Heiko
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