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Biomedical subjects

Stephen F Madden

Publications and source records attributed to Stephen F Madden.

3 recordsLinked to original sources

Integrating transcription factor binding site information with gene expression datasets.

MOTIVATION: Microarrays are widely used to measure gene expression differences between sets of biological samples. Many of these differences will be due to differences in the activities of transcription factors. In principle, these differences can be detected by associating motifs in promoters with differences in gene expression levels between the groups. In practice, this is hard to do. RESULTS: We combine correspondence analysis, between group analysis and co-inertia analysis to determine which motifs, from a database of promoter motifs, are strongly associated with differences in gene expression levels. Given a database of motifs and gene expression levels from a set of arrays, the method produces a ranked list of motifs associated with any specified split in the arrays. We give an example using the Gene Atlas compendium of gene expression levels for human tissues where we search for motifs that are associated with expression in central nervous system (CNS) or muscle tissues. Most of the motifs that we find are known from previous work to be strongly associated with expression in CNS or muscle. We give a second example using a published prostate cancer dataset where we can simply and clearly find which transcriptional pathways are associated with differences between benign and metastatic samples. AVAILABILITY: The source code is freely available upon request from the authors.

Algorithms↗

ETV4 and Myeov knockdown impairs colon cancer cell line proliferation and invasion.

We have identified novel colorectal cancer-associated genes using NCBI's UNIGENE cDNA libraries. Colon cancer libraries were examined using Digital Differential Display and disease-associated genes were selected. Among these were ETV4 and MYEOV, novel colorectal cancer-associated genes. Samples of matched normal and neoplastic colon were obtained from human subjects and gene expression was quantified using real-time PCR. ETV4 gene expression was significantly increased in colonic neoplasia in comparison to matched normal colonic tissue (p<0.05). Myeov expression was also increased in colon neoplasia in comparison to matched normal tissue. The effect of siRNA-mediated knockdown of ETV4 and Myeov on cell proliferation and invasion was assessed. ETV4 knockdown resulted in a 90% decrease in cell proliferation (p<0.05) and a 67% decrease in cell invasion. Myeov knockdown resulted in a 48% decrease in cell proliferation (p<0.05) and a 36% decrease in cell invasion. These data suggest that ETV4 and Myeov may provide novel targets for therapeutic intervention.

Adenovirus E1A Proteins↗

Digital extractor: analysis of digital differential display output.

Digital Extractor is a program for the high-throughput processing of data sets derived from digital differential display-based comparisons of EST libraries. These comparisons can be utilized to identify discrete subsets of genes whose expression is restricted to distinct tissue types. The program facilitates these investigations by permitting parallel annotation of genes identified as being differentially expressed.

Database Management Systems↗