Signaling biomarker pattern discovery using reverse phase protein microarray

Understanding the molecular mechanism of aging will allow human beings to develop rationale strategies for therapeutic interventions in aging related diseases. The goal of this study is to investigate the effect of a new protein, Klotho protein, on FGF (fibroblast growth factor) signaling. To identify the signaling molecules, two emerging technologies, high-throughput siRNA (small inference RNA) and reverse phase protein microarray (RPPM) are utilized. To quantitatively analyze the patterns of siRNA knockdowns, we present a Discriminative Feature Pattern Identification System (DFPIS) to identify contributing nuclear hormone receptors. Computational analysis results using HEK293 (human embryonic kidney) cells knocked down from siRNAs and screened by protein microarray were presented.

[1]  Richard A. Miller,et al.  Lifespan extension and delayed immune and collagen aging in mutant mice with defects in growth hormone production , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[2]  G. Ruvkun,et al.  A phosphatidylinositol-3-OH kinase family member regulating longevity and diapause in Caenorhabditis elegans , 1996, Nature.

[3]  Martin Holzenberger,et al.  IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice , 2003, Nature.

[4]  Tadashi Kaname,et al.  Mutation of the mouse klotho gene leads to a syndrome resembling ageing , 1997, Nature.

[5]  U. Alon,et al.  Broad patterns of gene expression revealed by clustering analysis of tumor and normal colon tissues probed by oligonucleotide arrays. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[6]  K. Rosenblatt,et al.  Regulation of Fibroblast Growth Factor-23 Signaling by Klotho* , 2006, Journal of Biological Chemistry.

[7]  M. Tatar,et al.  A Mutant Drosophila Insulin Receptor Homolog That Extends Life-Span and Impairs Neuroendocrine Function , 2001, Science.

[8]  Animesh Nandi,et al.  Suppression of Aging in Mice by the Hormone Klotho , 2005, Science.

[9]  Jung Hun Oh,et al.  Prediction of labor for pregnant women using high-resolution mass spectrometry data , 2006, Sixth IEEE Symposium on BioInformatics and BioEngineering (BIBE'06).

[10]  Prem Gurnani,et al.  Pegylated, steptavidin-conjugated quantum dots are effective detection elements for reverse-phase protein microarrays. , 2005, Bioconjugate chemistry.

[11]  M. Razzaque,et al.  Premature aging‐like phenotype in fibroblast growth factor 23 null mice is a vitamin D‐mediated process , 2006, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[12]  K. Rosenblatt,et al.  Regulation of Oxidative Stress by the Anti-aging Hormone Klotho*♦ , 2005, Journal of Biological Chemistry.

[13]  Jiawei Han,et al.  Discriminative Frequent Pattern Analysis for Effective Classification , 2007, 2007 IEEE 23rd International Conference on Data Engineering.

[14]  E. Hafen,et al.  Extension of Life-Span by Loss of CHICO, a Drosophila Insulin Receptor Substrate Protein , 2001, Science.

[15]  Kotagiri Ramamohanarao,et al.  Fast discovery and the generalization of strong jumping emerging patterns for building compact and accurate classifiers , 2006, IEEE Transactions on Knowledge and Data Engineering.

[16]  C. Kenyon The Plasticity of Aging: Insights from Long-Lived Mutants , 2005, Cell.

[17]  K. Fukuda,et al.  Klotho, a gene related to a syndrome resembling human premature aging, functions in a negative regulatory circuit of vitamin D endocrine system. , 2003, Molecular endocrinology.