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16. Chromosome 16 general aims. 16. Bioinformatic analysis of chromosome 16. Cell type (s) selection . Trascriptomic and proteomic detailed analysis . Expression , purification and characterization of proteins encoded by chromosome 16 that have not been described so far .
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16 Chromosome 16 general aims 16 Bioinformaticanalysis of chromosome 16. Celltype(s) selection. Trascriptomic and proteomicdetailedanalysis. Expression, purification and characterization of proteinsencodedbychromosome 16 thathavenotbeendescribed so far. Development of MRM methodsforthequantification of themostabundantproteinspeciesencodedbyeach of thechromosome 16 genes. Identification, characterization and quantification of proteinvariantsfromchromosome 16 genes. Definition of SOP Development of bioinformaticenvironment. Biobanking.
16 Bioinformaticanalysis of chromosome 16 16 • General description. Diseasesrelated. Biologicalfunctions. • Proteincoding genes. Unknownproteins. • Celltypeexpressionpattern (gene and proteinlevel). • Availability of proteinexpressionresources and trappingreagents.
Top 15 Biofunctionsrepresented in chromosome 16. IPA analysis
16 Genes onChromosome 16 16 ENSEMBL UNIPROTKB • Unknownproteins are presentneither in UNIPROT nor in GPMDB. • GPMDB thresholdwasloge<-5 GPMDB
16 DiseasesmappingonChromosome 16 16 OMIM CANCER OBESITY NEURODEGENERATIVE Inflammation Autoinmune diseases Metabolism Mitochondria
16 Expression of chromosome 16 proteincoding genes. Celltype 16 More than 75% of proteincoding genes of chromosome 16 are expressed in lymphoidcells
16 Proteintoolsalreadyavailable. Expression and capture 16 Human Protein Atlas SHPP
Protein Sequencing Team Dr. José M. Mato / Dr. Félix Elortza CIC-BioGUNE, ProteoRed, Bilbao Dr. Joaquin Abian Autonomous University of Barcelona- CSIC Mix Unit(CSIC-UAB), ProteoRed, Barcelona Dr. Manuel Sanchez del Pino Felipe Princess Research Center (CIPF), ProteoRed, Valencia Dr. Eliandre de Oliveira ParcCientífic de Barcelona (PCB), ProteoRed, Barcelona Dr. Ignacio Casal Biology Research Center-CSIC (CIB-CSIC), ProteoRed, Madrid Jesus M. Arizmendi Basque Country University ProteoRed, Bilbao Protein Micro Array & Peptide Standard Team Dr. Juan P Albar National Center for Biotechnology-CSIC (CNB-CSIC), ProteoRed, Madrid Dr. Manuel Fuentes Centro de Investigación del Cáncer/IBMCC (USAL/CSIC), Salamanca MRM-Protein Platform Team Dr. Juan P Albar National Center for Biotechnology-CSIC (CNB-CSIC), ProteoRed, Madrid Dr. Fernando Corrales CIMA-University of Navarra ProteoRed, Pamplona Dr. Francesc Canals Valld'HebronInstitutd'Oncologia (V.H.I.O.) ProteoRed, Barcelona Dr. Concha Gil Madrid Science Park-Madrid Computensis University (PCM-UCM), ProteoRed, Madrid Dr. Manuel Sanchez del Pino Felipe Princess Research Center (CIPF), ProteoRed, Valencia Dr. Fernando Vivanco Jimenez Díaz Foundation (FJD), Madrid Dr. Francisco Blanco Instituto de InvestigacionBiomedica (INIBIC), ProteoRed, La Coruña Dr Silvia Barceló Aragón Health Sciences Institute (IACS), Zaragoza Clinical Health Care & Biobanking Team Dr. Francisco Blanco Instituto de InvestigacionBiomedica (INIBIC), ProteoRed, La Coruña Dr. Cristobal Belda Severiano Ballesteros Foundation La Paz Hospital, Madrid Dr. Fernando Vivanco Jimenez Díaz Foundation (FJD), Madrid Dr. Adolfo López de Munain InstitutoBiodonostia San Sebastian Dr. Manuel Morente (considered for inclusion in the consortium) Spanish National BioBanking Network CNIO, Madrid Bioinformatics Team Dr. Juan P Albar National Center for Biotechnology-CSIC (CNB-CSIC), ProteoRed, Madrid Dr. Fernando Corrales CIMA-University of Navarra ProteoRed, Pamplona
16 Workplanproposalfor 2012 16 • As lymphocytesexpress more than 75% chr16 proteincoding genes, periferalbloodlymphocyte (PBL), orlymphoidcelllines are proposed. Epithelialcelllines and/orfibroblastsmightcomplement. • Once decidedthebiologicalsource: • Prepare a master sampletodistributetoallparticipatinglabs (CIMA, others). • Characterizethetranscriptometo define the actual chr16’s gen set expressed and mostimportantlywhich genes are notexpressed (CIMA). • Characterizetheproteome in detail(proteinsequencingteam). Itmayrequirefractionation. • Expression, purification, and characterization of 22 unknownproteinsavailable in NAPPA collection (CIC, sequencingteam...).
16 Workplanproposalfor 2012 16 • Development of SRM quantitativeassays (MRM team). • Proteins (862) will be distributed in known (751) and unknowngroups (111) and thestudywill be performedalong 3 years, starting in 2012 (184 proteins). • Protein packs will be assignedtoeach of the 8 MRM groups (23), includingequalproportion of known (20, withdifferentrange of theoreticaldifficulty) and unknownproteins (3). • Eachgroupwilldevelopthe MRM assaysusingthe master sample (thismightrequirethe use of syntheticpeptidesduringtherefinementsteps). • Once developed, theassayswill be validatedby 2 additionalgroups. Finally, thequantitativeassaywill be set up using heavy peptides. • Definition of Bioinformaticstandards and SOPs (Bioinformaticgroup, all). • Definition of Biobankingstrategy, standards... in collaborationwiththeSpanishBiobankingPlatform (Biobankgroup, all). • Definition of theDisease Pilar. Likelydefined in theversion of the SHPP for chr19.
16 Chromosome 16 workplan 16 2012 2013 2014 • Bioinfirmatic study • MRM for 184 proteins • MRM for 339 proteins • MRM for 339 proteins • SOP, bioinformatic procedures, formats, data banks, etc. • Validation of MRM assays (3 groups, immunoreagents, correlation with gene expression) • Clinical samples. Disease-related changes on protein abundance. Biomarkers • Biobanking 2015 2016 2017 • Validation of MRM assays (3 groups, immunoreagents, correlation with gene expression) • Clinical samples. Disease-related changes on protein abundance. Biomarkers • Biobanking
BIOBANKING. Healthy / Pathologicalsamples: tissue, cells, organs, fluids (plasma/urine..) Colorectalcancer CIB-CSIC CIPF Hepaticdiseases CIC bioGUNE CIMA Cardiovascular diseases IIS-FJD Rheumatologicdiseases INIBIC Neurodegenerative IdiPAZ BioDonostia Chromosome - 16 Innovativeasays Therapeuticdevelopment Early diagnosis test Novel Biomarkers New bioinformatictools Novel proteinarrays Systembiologydiseases MS-Imaging Tissuemaps Novel drug targets HUMAN PROTEOME
MICINN ISCIII SteeringCommittee Analytical Gene/chromosomecentric Research Diseasecentric Bioinformatics MS andAbbasedquantitativemethods Open accessrepositories Hallmarksofdisease Potentialbiomarkersandtherapeutic targets Biotechs MICINN Designofprototypes Quantitationoftargetproteins Pharmas ISCIII CNB UCM CIB FJD CicBiogune CIMA CIPF UAB PCB VallD’Hebron USAL La Paz Juan Canalejo Clinicaldevices Personalized medicine
BoardofDirectors Project Manager ExecutiveCommittee Technical Director Finance Director WG 1 WG n . . . . . . . . . . . . . . . . . WorkingGroups ResearchUnits RU 1a RU 1x RU na RU nx . . . . . . . .