An integrative proteotranscriptomic approach identifies new substrates and downstream pathways for
Congyu Lu(1,2), Neha Sindhu(1,2), Jessica Rainey(1), Xiaolu Xu(1), Shawn W. Polson(2,3), Jing Qiu(2,4), and Shuo Wei(1,2) 1. Department of Biological Sciences, University of Delaware, 2. Center for Bioinformatics and Computational Biology, University of Delaware, 3. Department of Computer and Information Sciences, University of Delaware, 4. Department of Applied Economics and Statistics, University of Delaware
Poster # 66
ADAM9 (A disintegrin and a metalloprotease 9) is a single-pass type I transmembrane protein with proteolytic activity at its extracellular protease domain. Its overexpression is associated with several diseases including many solid tumors. For tumors, ADAM9 is reported to be associated with progression, aggressiveness, and metastasis. Juxtaposing with the fact that the loss of ADAM9 has little reported consequence aside from retinal degradation, the protein is potentially an excellent therapeutic target for multiple diseases including, but not limited to, solid tumors.We use omics techniques to find the direct proteolytic substrates and indirect targets of ADAM9 in colorectal cancer cells. Transcriptome and Cellular Proteome of ADAM9 knockdown cells are integrated using the O2PLS technique. The integrated analysis of the differential gene and protein expression along with the direction in which they are corrected with ADAM9 differential expression is used to predict its transcriptional and post-transcriptional targets. Further, the post-transcriptional targets that are negatively correlated with ADAM9 which are also surface proteins are predicted to be candidate substrates that could be directly cleaved by ADAM9. Some of these in-silico predictions are further confirmed in our lab using western blotting.