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Physiol. Genomics (May 15, 2002). doi:10.1152/physiolgenomics.00035.2002
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Articles in PresS, published online ahead of print May 15, 2002
Physiol Genomics, 10.1152/physiolgenomics.00035.2002
Submitted on March 28, 2002
Accepted on May 8, 2002

The use of in silico data filtering to identify potential angiogenic targets from a large in vitro gene profile data set

Mary E Gerritsen1*, Robert Soriano2, Suya Yang1, Gladys Ingle1, Constance Zlot1, Karen Toy2, Jane Winer2, Aparna Draksharapu3, Franklin Peale3, Thomas D Wu4, and P. M Williams2

1 Cardiovascular Research, Genentech, South San Francisco, CA, USA
2 Molecular Biology, Genentech, South San Francisco, CA, USA
3 Pathology, Genentech, South San Francisco, CA, USA
4 Bioinformatics, Genentech, South San Francisco, CA, USA

* To whom correspondence should be addressed. E-mail: meg570{at}attbi.com.

The objective of this study was to use gene expression data from well-defined cell culture models, in combination with expression data from diagnostic samples of human diseased tissues, to identify potential therapeutic targets and markers of disease. Using Affymetrix oligonucleotide array technology, we identified a common profile of genes upregulated during endothelial morphogenesis into tube-like structures in three in vitro models of angiogenesis. Rigorous data selection criteria were used to identify a list of over 1000 genes whose expression was increased more than two-fold over base-line at either 4, 8, 24, 40 or 50 hours. To further refine and prioritize this list, we used standard bioinformatic algorithms to identify potential transmembrane and secreted proteins. We then overlapped this gene set with genes upregulated in colon tumors versus normal colon, resulting in a subset of 128 genes in common with our endothelial list. We removed from this list those genes expressed in 6 different colon tumor lines, resulting in a list of 24 putative, vascular-specific angiogenesis-associated genes. Three genes, gp34, stanniocalcin 1, GA733-1 were expressed at levels 10 fold or more in colon tumors compared to normal mucosa. We validated the vascular specific expression of one of these genes, STC-1, by in situ hybridization. The ability to combine in vitro and in vivo data sets should permit one to identify putative angiogenesis target genes in various tumors, chronic inflammation, and other disorders where therapeutic manipulation of angiogenesis is a desirable treatment modality.




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