1. Beyond TissueInfo: Functional Prediction Using Tissue Expression Profile Similarity Searches Rocky Mountains Bioinformatics 2007 Institute for Computational Biomedicine and Dept of Physiology and Biophysics, Weill Medical College of Cornell University New York, USA Fabien Campagne, Ph.D.

2. Tissue Expression Profile Similarity Searches TEPSS assumes that functionally related transcripts are co-expressed in subsets of tissues Expression measured with expressed sequence tags (dbEST and TissueInfo) The TEPSS approach formalizes similarity searches in tissue expression space and offers a computationally efficient solution See http://icb.med.cornell.edu/crt/tepss/ Hint: Google for ‘TEPSS’

3. TEPSS scores discriminate interacting protein pairs from non-interacting pairs 50,000 human protein-protein interactions High-quality interactions only (~1,000)

4. TEPSS prioritizes members of the cytosolic ribosome TEPSS prioritizes S- nitrosylation protein targets Combining signals from multiple transcripts TEPSS used with multiple transcripts is a flexible and effective candidate prediction approach Beyond TissueInfo: Functional Prediction using Tissue Expression Profile Similarity Searches Daniel Aguilar, Lucy Skrabanek, Steven S. Gross, Baldomero Oliva, Fabien Campagne. Submitted for publication Validation with leave-one-out lift curves

5. Ribosome screen: top predictions

6. Predicting targets of S-nitrosylation Training set from: Hao G, Derakhshan B, Shi L, Campagne F, Gross SS. SNOSID, a proteomic method for identification of cysteine S-nitrosylation sites in complex protein mixtures. PNAS 2006 Protein post-translational modification by nitric oxyde

7. Summary and conclusions Tissue Expression Profile Similarity Searches (TEPSS) TEPSS scores can discriminate pairs of proteins reported to interact from pairs of proteins not reported to interact. TEPSS effectively prioritizes members of the ribosome and S- nitrosylation (SNO) protein targets, in whole genome screens. Approach predicts non-trivial members of cytosolic ribosome Application to S-nitrosylation protein targets suggests candidates for experimental validation TEPSS does not use sequence similarity and thus can be used in complement to methods that do. Open-source, see http://icb.med.cornell.edu/crt/tepss/ for programs, source code, and data.

8. Acknowledgments Weill Medical College of Cornell University Dept. of Pharmacology Gang Hao Steven S. Gross Institute for Computational Biomedicine Lucy Skrabanek (EST data curation) Universitat Pompeu Fabra, Barcelona, Spain Instituto Municipal de Investigación Medica Daniel Aguilar Baldo Oliva