Virginia G. Piper Center for Personalized Diagnostics Chromosome 10 Joshua LaBaer, M.D., Ph.D. Konstantinos Petritis, Ph.D. Virginia G. Piper Center for.

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Presentation transcript:

Virginia G. Piper Center for Personalized Diagnostics Chromosome 10 Joshua LaBaer, M.D., Ph.D. Konstantinos Petritis, Ph.D. Virginia G. Piper Center for Personalized Diagnostics Biodesign Institute, ASU Joshua LaBaer, M.D., Ph.D. Konstantinos Petritis, Ph.D. Virginia G. Piper Center for Personalized Diagnostics Biodesign Institute, ASU Hupo September 13-16, 2013 Yokohama Japan

Virginia G. Piper Center for Personalized Diagnostics Number of Genes and Proteins on Chromosome 10 ~760 genes and ~1,500 proteins in Chr 10

Virginia G. Piper Center for Personalized Diagnostics RET proto-oncogene PTEN tumor suppressor Wnt signaling Vesicle transport (regulation of ARF proteins) Metabolic pathways, esp., oxidation/reduction Intracellular signaling, ANX and ArfGap domains Protein interactions, ANK, LH2 and PDZ domains 155 diseases in OMIM, including papillary thyroid carcinoma, glaucoma, macular degeneration and epilepsy Enriched Pathways on Ch 10

Virginia G. Piper Center for Personalized Diagnostics Protein Domains and Biological Pathways Enriched in Chromosome 10 Source: SMART Source: Reactome

Virginia G. Piper Center for Personalized Diagnostics Chromosome 10 Genes with Missing Protein-Level Evidence

Virginia G. Piper Center for Personalized Diagnostics Collection of evidence at transcript, peptide, and protein levels on Chr 10 Identification of unreported target proteins with transcript-level evidence Publically available RNAseq cell line datasets (e.g. Frida et al) Publically available RNAseq cell line datasets (e.g. Frida et al) In-house and public (e.g. TCGA) RNA-seq cancer datasets In-house mass spec database Peptides mapping to genomic coordinates Identification of cell lines and/or tissues potentially expressing target proteins Mass Spectrometry on target cells/tissues Data integration, visualization, and analysis for novel peptide evidence IVTT protein expression and LC-QQQ characterization of proteotypic peptides Targeted Proteomics Approach for Obtaining Protein Evidence Phase I Phase II

Virginia G. Piper Center for Personalized Diagnostics DNASU Clones of 210 Genes without Protein Evidence Targeted Proteomics Approach based on IVTT

Virginia G. Piper Center for Personalized Diagnostics Frida et al (from the last C-HPP issue of JPR) Selection of Target Cell Lines/Tissues for Mass Spectrometry to Search the 210 Missing Proteins

Virginia G. Piper Center for Personalized Diagnostics Data Integration and Visualization on IGV

Virginia G. Piper Center for Personalized Diagnostics GRID1 Data Integration and Visualization on IGV

Virginia G. Piper Center for Personalized Diagnostics PTPN20B BMS1P1 Data Integration and Visualization on IGV

Virginia G. Piper Center for Personalized Diagnostics PCDH15 Data Integration and Visualization on IGV

Virginia G. Piper Center for Personalized Diagnostics Josh LaBaer Lab Jin Park C-HPP Chromosome 10 Project Team Konstantinos Petritis Lab Meraj Aziz Patrick Pirrotte