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Alyssa Bumbaugh Scott H. Harrison

Loss of Adhesion Phenotype Correlated with Loss of Conservation of Extracellular Region and C-terminus in Cadherin. [Picture from wikipedia]. Alyssa Bumbaugh Scott H. Harrison Pennsylvania State University, Altoona College Indiana University Purdue University Indianapolis

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Alyssa Bumbaugh Scott H. Harrison

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  1. Loss of Adhesion Phenotype Correlated with Loss of Conservation of Extracellular Region and C-terminus in Cadherin [Picture from wikipedia] Alyssa Bumbaugh Scott H. Harrison Pennsylvania State University, Altoona College Indiana University Purdue University Indianapolis Asit Saha Central State University, Wilberforce Ohio ASM/BioQUEST March 7, 2008 Bioinformatics Institute Group Research Project Harrison Bumbaugh B Q * Saha *LABORATORIES“Rideo, Ergo sum” est. 2008

  2. Our Study • - Profiling theTwo Roles for Cadherin in Healthy Human Physiology-RSCB Protein Data Bank (http://www.rscb.org) - showed structural differences between regular E-cadherin and N-cadherin related to respective roles of the cadherin protein for: a) cell-to-cell adhesion; and b) mobility. • - Finding Healthy and Disease-Related Protein Sets -Use PIR (Protein Information Resource; http://pir.georgetown.edu) and HIP2 (Healthy Human Individuals’ Integrated Plasma Protein; http://bio.informatics.iupui.edu/HIP2) to find two related sets of cadherin proteins (a putative disease set and a putative healthy set) based on MS/MS detection counts of peptides. • - Inspecting Sequence Alignments for Correlation with Structural and Indications of Different Roles -Alignment with CLUSTALW (using http://biologyworkbench.sdsc.edu); Local regional alignments with SIM - Local similarity program; http://www.expasy.ch/tools/sim-prot.html.

  3. Cadherin, a dual role for adhesion and mobility/lubrication membrane • = loss of structure of extracellular domainand loss of C-terminus adhesion sequence • Cancer implicated with N-cadherin being expressed in breast tissue [Nieman et al, 1999; Hazan et al, 2000] • One allele deleted and the other mutated of cadherin also corresponds with cancer [Berx and Van Roy, 2001] Extracellular regions intracellular intracellular Neural cadherin [Made with http://consurf.tau.ac.il] Epithelial cadherin

  4. Sequence Alignment of Cadherin Proteins - Putative Disease Set of Cadherin Proteins based on Reduced MS/MS Detection Counts in Healthy Human Individual's Integrated Plasma Proteome Database (http://bio.informatics.iupui.edu/HIP2/)

  5. Neighbor-joining Tree of “Healthy” versus “Disease” Sets of Cadherin Proteins 38 39 26 0 15 0 0 2 2 • Neighbor-joining tree based on 500 bootstrap replications • Cadherin from disease cohort indicated with solid circle • Cadherin from healthy cohort indicated with open circle • Detection counts in Healthy Human Individual's Integrated Plasma Proteome Database (http://bio.informatics.iupui.edu/HIP2/) shown in blue

  6. 20 consecutive locally aligned regions for pairwise protein comparisons(40 to 180 aa windows)…Within-Group Comparisons vs vs

  7. 20 consecutive locally aligned regions for pairwise protein comparisons (40 to 180 aa windows)…a Between-Group Comparison

  8. Conclusions • Loss of conservation trends to the latter portion (toward the C-terminus) of the cadherin protein when there is association with motility and disease. • This may enable prognosis of cellular phenotype of cancer cells and their invasive motility.

  9. Acknowledgements Our BioQUEST Instructors and ASM Facilitators! • Sam Donovan • Michelle Godinez • Brad Goodner • Kelly Gull • John Jungck • Anton Weisstein

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