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A Spanish Human Proteome Project (sHPP)

A Spanish Human Proteome Project (sHPP). La Cristalera, Miraflores de la Sierra, Madrid, August 28-29th, 2012 Juan P Albar, ProteoRed-ISCIII, CNB-CSIC. A SPANISH HUMAN PROTEOME PROJECT (SHPP) Preliminary proposal Index Introduction International context Chromosome/gene centric approach

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A Spanish Human Proteome Project (sHPP)

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  1. A Spanish Human Proteome Project (sHPP) La Cristalera, Miraflores de la Sierra, Madrid, August 28-29th, 2012 Juan P Albar, ProteoRed-ISCIII, CNB-CSIC

  2. A SPANISH HUMAN PROTEOME PROJECT (SHPP) • Preliminary proposal • Index • Introduction • International context • Chromosome/gene centric approach • The HPP technological pillars • Protein annotation and database compilation • The Spanish Participation in the Human Proteome Project • General and Specific Aims • General aims • Specific aims • Members of the Spanish Consortium • Description of the groups • ProteoRed presence in the Spanish consortium • Working Plan • Work package list • Work package description • Financing • Spanish Consortium Structure • Benefit for Spain

  3. Spanish HPP Consortium: Current Developments on the Characterization of the Proteins Encoded by the Chromosome 16" 5th C-HPP Consortium Workshop The Chromosome-Centric Human Proteome Project May 5, 2012, Beijing Juan-Pablo Albar (Chair) Francisco Blanco (Co-Chair) Fernando Corrales (Co-Chair)

  4. A Spanish Human Proteome Project (sHPP) Preliminary proposal San Sebastian, July 9th, 2012 Juan P Albar, ProteoRed-ISCIII, CNB-CSIC

  5. The Human Proteome Project Launch Sydney HUPO2010 23 September 2010 Geneva HUPO2011 12 September 2011 Sydney September 23 Human Proteome Project

  6. The Mission of the HPP HPP will deliver a comprehensive map of the human proteins in their biological context. HPP will provide tools for the scientific community that will allow each scientist to design experiments in a better way, as the Human Genome Project did. HPP will inspire, beyond the scientific community, other stakeholders for diagnosis, prevention, therapy and cure of diseases and improved health worldwide. Sydney September 23 Human Proteome Project

  7. A gene-centric proteome project Map the human proteins (gene by gene): • Molecular (isoforms) • Sub-cellular (localization) • Cells, tissues and organs (expression) • Interaction networks • Plasma/serum (abundance) Use all available technology platforms: • Mass spectrometry • Antibodies (immunotechnologies) • Gene fusions (GFP) Sydney September 23 Human Proteome Project

  8. C-HPP teams by April 24th, 2012. The C-HPP Consortium internal information

  9. HPP technologic pillars Legrain et al. MCP 2011

  10. Flow of the overall procedures of the C-HPP work

  11. Spanish HPP Consortium: Current Developments on the Characterization of the Proteins Encoded by the Chromosome 16" 5th C-HPP Consortium Workshop The Chromosome-Centric Human Proteome Project May 5, 2012, Beijing Juan-Pablo Albar (Chair) Francisco Blanco (Co-Chair) Fernando Corrales (Co-Chair)

  12. Chromosome 16

  13. 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. Configuration of the B-D pilar fortheSpanish HPP consortium.

  14. Top 15 Biofunctionsrepresented in chromosome 16. IPA analysis

  15. 16 Genes onChromosome 16 16 More than85 % of proteincoding genes of chromosome 16 are expressed in lymphoidcells, epitelial cells and fibroblasts.

  16. 16 DiseasesmappingonChromosome 16 16 OMIM CANCER OBESITY NEURODEGENERATIVE AUTOINMUNE DISEASES Metabolism Mitochondria Inflammation

  17. Development of bioinformatic environment: Spanish HPP will join the different resources to provide an unique enquiring system NProt PRIDE PAtlas External repositories Data standards submission (ProteomeXchange) Proteomics results + + Emsembl Upcoming UProt GPMDB

  18. 16 Workplanproposal 16 • Characterize the transcriptome to define the actual chr16’s gen set expressed and most importantly which genes are not expressed in the three selected cell types. • Characterize the proteome in detail. • Expression, purification, and characterization of 22 unknown proteins available in NAPPA collection. • Development of SRM quantitative assays. • Proteins (862) will be distributed in known (562) and unknown groups (300) and the study will be performed along 3 years, starting in 2012 (214 proteins). • Protein packs will be assigned to each of the 8 MRM groups (24), including equal proportion of known (20, with different range of theoretical difficulty) and unknown proteins (4). • Unknown proteins will be first searched by targeted discovery (TD) and relevant information resulting from this studies will be used to design MRM assays. TD groups (9) will analyze 54 proteins the first year. • Each group will use the master sample (this might require the use of synthetic peptides during the refinement steps). TD will be done in all three selected cell lines. Regarding MRM, a pool of the three cell lines will be used for the 20 known proteins. Decision on using a pool or a particular cell line for the unknown proteins will be taken in light of the results from TD. • Once developed, the assays will be validated by 2 additional groups. Finally, the quantitative assay will be set up using heavy peptides. • Definition of Bioinformatic standards and SOPs. • Definition of Biobanking strategy, standards... in collaboration with the Spanish Biobanking Platform.

  19. 16 Chromosome 16 timeline 16 2012 2013 2014 Bioinfirmatic study Master sample Transcriptomic study Targeted discovery (300 proteins) MRM for 204 proteins MRM for 329 proteins MRM for 329 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

  20. SHPP-16 111 Unknow Proteins 735 KnowProteins Platform BD-HPP Platform C-HPP BIOBANK/ISCIII Proteo-Red/ISCIII Biology Cells/Tissues Diseases: Pathogenesis Diagnostic Prognosis Treatment

  21. http://www.proteored.org Who we are • ProteoRed, an initiative for the coordination, integration and development of 20 proteomics facilities placed all over Spain. • ProteoRed use to organize and participate in multi-centric studies that aims to evaluate the robustness and reproducibility of different proteomics workflows. • ProteoRed organization has played an active role in the HUPO-PSI activities, always in close relation with the developments and reviews of different MIAPE modules.

  22. Geographical organization Node 2 J. Mato - CIC-bioGUNE F. Corrales – CIMA JM. Arizmendi - UPV Assoc. to node 4 F.J. Blanco - INIBIC Node 3 J. Abian - LP-CSIC/UAB J. Arribas - HUVH S. Martínez - PCB D. Andreu - UPF FX. Avilés - IBB UAB O. Bachs - UB * . Node 4 X. Bustelo - CIC * Central Structure JP. Albar - CNB J. Mato - CIC-bioGUNE J. Abian - LP-CSIC/UAB Geneva Jean Charles Sanchez - UG Portugal Ana Coelho - ITQB Deborah Penque - ProCura Node 5 M. Sánchez del Pino – CIPF R. Bru - UA Node 1 JP. Albar - CNB C. Gil - PCM-UCM A. Marina - CBMSO - Assoc. To Node 5 P. Carrasco - UV Assoc. to Node 1 I. Casal - CIB Node6 JA. Bárcena - UCO

  23. CIBER-Obesity RETIC of Cancer RETIC of Rheumatic CIBERNed SHPP-16 BD-HPP Platform Coordinator: Francisco J. Blanco ClinicalResearch Biomarkers (D/P/P/T) 1st Phase: KnownProteins 2nd Phase: UnknownProteins CAIBER/ISCIII BIOBANK/ISCIII Cancer Chair: Co-Chair: I. Casal) RheumaticDiseases: Chair: FJ. Blanco Co-Chair: JP Albar Obesity Chair: J Prieto Co-Chair: F. Corrales NeurologicDisorders Chair: A. Lopez- Munain Co-chair:JM Arizmendi Cardiovascular Diseases: Chair: L Rodriguez-Padial Co-Chair: F. Vivanco InfectiiousDiseases: Chair: J Fortun Co-Chair: C. Gil RETIC-Cardiov.

  24. HOSPITALES INSTITUTOS DE INVESTIGACIÓN CENTROS DE INVESTIGACIÓN REDES COOPERATIVAS RHEUMATIC & MUSCLOSKELETAL DISEASES Dr. F. BLANCO OBESITY/LIVER DISEASES Drs J. PRIETO & F. CORRALES NEUROLOGICAL DISEASES Dr A. LOPEZ DE MUNAIN Chr16-HPP Proteomics Platforms SPANISH NATIONAL BIOBANK NETWORK-ISCIII Dr M. MORENTE CARDIOVASCULAR DISEASES Dr F. VIVANCO & JLR: PADIAL INFECTIOUS DISEASES Drs C. GIL & J. FORTÚN CANCER Drs C. BELDA & I. CASAL

  25. HOSPITALES INSTITUTOS DE INVESTIGACIÓN CENTROS DE INVESTIGACIÓN REDES COOPERATIVAS MINISTERIO DE ECONOMIA Y COMPETITIVIDAD PLATAFORMAS PROTEÓMICAS ASOCIACIONES DE PACIENTES MINISTERIO DE INDUSTRIA HPP FARMAINDUSTRIA MINISTERIO DE SANIDAD MINISTERIO DE EDUCACIÓN ASEBIO EMPRESAS AFINES COMUNIDADES AUTÓNOMAS INVERSIÓN PRIVADA

  26. MINECO ISCIII SteeringCommittee Analytical (C-HPP) Gene/chromosomecentric B-D initiatives Diseasecentric Bioinformatics MS andAbbasedquantitativemethods Open accessrepositories Hallmarksofdisease Potentialbiomarkersandtherapeutic targets Biotechs MINECO Designofprototypes Quantitationoftargetproteins Pharmas ISCIII CNB UCM CIB FJD CicBiogune CIMA CIPF UAB PCB Vall D’Hebron USAL La Paz INIVIC Clinicaldevices Personalized medicine

  27. CHROMOSOME-16 CONSORTIUM STRUCTURE BoardofDirectors Project Manager Executive Committee Technical Director Finance Director WG 1 WG 2 WG 3 WG 5 WG 4 Working Groups RU1a/1b RU 2a/2h RU 3a/3g RU 4a/4e RU 5a/5g Research Units

  28. WG 1.-Protein Micro Array & Peptide Standard Team RU1a (Protein Micro Array and ProteinExpressionTeam) Dr. Manuel Fuentes CIC/IBMCC (USAL/CSIC), Salamanca RU1b (Peptide Standard Team) Dr. Juan P Albar CNB-CSIC, ProteoRed, Madrid Scientific Researchers: Scientific Researchers: F. Roncal M. Lombardía

  29. WG 2.-S/MRM-Protein Platform Team RU2a Dr. Juan P. Albar CNB-CSIC, ProteoRed, Madrid RU2b Dr. Fernando Corrales CIMA-UN ProteoRed, Pamplona RU2c Dr. Francesc Canals V.H.I.O. ProteoRed, Barcelona RU2d Dr. Concha Gil PCM-UCM ProteoRed, Madrid RU2e Dr. Manuel Sanchez del Pino UV ProteoRed, Valencia RU2f Dr. Fernando Vivanco / Dr. M.E Barderas FJD,Madrid/HNP, Toledo RU2g Dr. Francisco Blanco INIBIC, ProteoRed, La Coruña RU2h Dr. Silvia Barceló IACS, Zaragoza (Provisional) • Scientific Researchers: • M. Marcilla • S. Gharbi • Alpízar • C. González Scientific Researchers: Scientific Researchers: Scientific Researchers: Scientific Researchers: Scientific Researchers: Scientific Researchers: Scientific Researchers:

  30. WG 3.-Protein Sequencing Team RU3a Dr. José M. Mato / Dr. Félix Elortza CIC-BioGUNE, ProteoRed, Bilbao RU3b Dr. Joaquin Abian IIBB-CSIC ProteoRed, Barcelona RU3c Dr. Manuel Sanchez del Pino UV, ProteoRed, Valencia RU3d Dr. Eliandre de Oliveira PCB, ProteoRed, Barcelona RU3e Dr. Ignacio Casal CIB-CSIC, ProteoRed, Madrid RU3f Dr. Jesus M. Arizmendi UPV ProteoRed, Bilbao RU3g Dr. Juan P. Albar CNB-CSIC, ProteoRed, Madrid Scientific Researchers: Scientific Researchers: Scientific Researchers: Scientific Researchers: Scientific Researchers: Scientific Researchers: • Scientific Researchers: • Paradela • R. Navajas

  31. WG 4.-Bioinformatics Team RU4a Dr. Juan P Albar CNB-CSIC, ProteoRed, Madrid RU4b Dr. Fernando Corrales CIMA-UN ProteoRed, Pamplona RU4c Dr. Joaquin Abian IIBB-CSIC ProteoRed, Barcelona RU4d Dr. Concha Gil PCM-UCM ProteoRed, Madrid RU4e Dr. Jesus M. Arizmendi UPV ProteoRed, Bilbao Scientific Researchers: • Scientific Researchers: • Medina • S. M-Bartolomé Scientific Researchers: Scientific Researchers: Scientific Researchers:

  32. WG 5.-Clinical Health Care & Biobanking Team (S_B/D-HPP) RU5a Dr. Francisco Blanco INIBIC, ProteoRed, La Coruña RU5b Dr. Cristobal Belda FSB, La Paz Hospital, Madrid (Provisional) RU5c Dr. Rodríguez Padial/ Dr. Fernando Vivanco / Dr. M.E Barderas FJD, Madrid/HNP, Toledo RU5d Dr. Adolfo López de Munain Inst. Biodonostia S. Sebastian RU5e Dr. Fernando Corrales CIMA-UN ProteoRed, Pamplona RU5f Dr. Concha Gil PCM-UCM ProteoRed, Madrid RU5g Dr. Manuel Morente SNBN, CNIO, Madrid (considered for inclusion in the consortium) Scientific Researchers: Scientific Researchers: Scientific Researchers: Scientific Researchers: Scientific Researchers: Scientific Researchers: Scientific Researchers:

  33. WG1-Protein Micro Array & Peptide Standard Team RU1a (Peptide standardization Team):Dr. Manuel Fuentes Centro de Investigación del Cáncer/IBMCC (USAL/CSIC), Salamanca RU1b (Protein Micro Array and Protein expression Team): Dr. Juan P Albar National Center for Biotechnology-CSIC (CNB-CSIC), ProteoRed, Madrid WG3-Protein Sequencing Team RU3a-Dr. José M. Mato / Dr. Félix Elortza CIC-BioGUNE, ProteoRed, Bilbao RU3b-Dr. Joaquin Abian IIBB, CSIC ProteoRed, Barcelona RU3c-Dr. Manuel Sanchez del Pino University of Valencia, ProteoRed, Valencia RU3d-Dr. Eliandre de Oliveira Parc Científic de Barcelona (PCB), ProteoRed, Barcelona RU3e-Dr. Ignacio Casal Biology Research Center-CSIC (CIB-CSIC), ProteoRed, Madrid RU3f-Dr. Jesus M. Arizmendi Basque Country University ProteoRed, Bilbao RU3g-Dr. Juan P Albar National Center for Biotechnology-CSIC (CNB-CSIC), ProteoRed, Madrid WG2-S/MRM-Protein Platform Team RU2a-Dr. Juan P Albar National Center for Biotechnology-CSIC (CNB-CSIC), ProteoRed, Madrid RU2b-Dr. Fernando Corrales CIMA-University of Navarra, ProteoRed, Pamplona RU2c-Dr. Francesc Canals Vall d'Hebron Institut d'Oncologia (V.H.I.O.),ProteoRed, Barcelona RU2d-Dr. Concha Gil Madrid Science Park-Computensis University (PCM-UCM), ProteoRed, Madrid RU2e-Dr. Manuel Sanchez del Pino Felipe Princess Research Center (CIPF), ProteoRed, Valencia RU2f-Dr. Fernando Vivanco / Dr. ME Barderas Jimenez Díaz Foundation (FJD), Madrid /National Paraplegics Hospital, Toledo RU2g-Dr. Francisco Blanco Instituto de Investigacion Biomedica (INIBIC), ProteoRed, La Coruña RU2h-Dr Silvia Barceló Aragón Health Sciences Institute (IACS), Zaragoza WG5-Clinical Health Care & Biobanking Team RU5a-Dr. Francisco Blanco Instituto de Investigacion Biomedica (INIBIC), ProteoRed, La Coruña RU5b-Dr. Cristobal Belda (Provisional) Severiano Ballesteros Foundation La Paz Hospital, Madrid RU5c-Dr. Rodriguez Padial/Dr. Fernando Vivanco/ Dr. ME Barderas Jimenez Díaz Foundation (FJD), Madrid /National Paraplegics Hospital, Toledo Ru5d-Dr. Adolfo López de Munain Instituto Biodonostia, San Sebastian RU5e-Dr. Fernando Corrales/J. Prieto CIMA-University of Navarra RU5f-Dr. Concha Gil PCM-Computensis University (PCM-UCM), ProteoRed, Madrid RU5g-Dr. Manuel Morente (considered for inclusion in the consortium) Spanish National BioBanking Network CNIO, Madrid WG4-Bioinformatics Team RU4a-Dr. Juan P Albar National Center for Biotechnology-CSIC (CNB-CSIC), ProteoRed, Madrid RU4b-Dr. Fernando Corrales CIMA-University of Navarra ProteoRed, Pamplona RU4c-Dr. Joaquin Abian IIBB, CSIC, ProteoRed, Barcelona RU4d-Dr. Concha Gil PCM-Computensis University (PCM-UCM), ProteoRed, Madrid RU4e-Dr. Jesus M. Arizmendi Basque Country University, ProteoRed, Bilbao

  34. Aims to achieve in the 1st Chr-16 Consortium Meeting • Evaluation of the strategy defined in the April 2nd S_HPP Meeting: S/MRM, AIMS, Shotgun, cell culture, protein expression, data base, bioinformatics platform, data workflow • Preparation of JPR manuscript, HUPO-Boston Posters… • 2012 Working plan (short and medium term)

  35. HUPO CONGRESS POSTERS (I) • RE:  Abstract log #322 Your abstract entitled Chromosome 16 Consortium: Current Developments on the Characterization of the Proteins Encoded by the Chromosome 16" (log #322) is formally accepted for poster presentation at the HUPO 11th Annual World Congress, September 9-13, 2012 in Boston, MA (USA). • RE:  Abstract log #146 Your abstract entitled Chromosome 16. Transcriptomic profiling of lymphocyte B Ramos cells, MCF-7 epithelial cells and CCD18 fibroblasts (log #146) is formally accepted for poster presentation at the HUPO 11th Annual World Congress, September 9-13, 2012 in Boston, MA (USA). • RE:  Abstract log #368  Your abstract entitled Profiling the Chromosome 16 by high-resolution data-dependent Mass Spectrometry (log #368) is formally accepted for poster presentation at the HUPO 11th Annual World Congress, September 9-13, 2012 in Boston, MA (USA). 

  36. HUPO CONGRESS POSTERS (II) • RE: Your abstract log# 758 for the HUPO2012 conference was submitted on 6/30/2012.The log number for your abstract is 758. Chromosome 16 Consortium: The Spanish B/D-C-HPP Initiative Juan P Albar; Jesus Fortun; Jesus Mari Arizmendi; Cristobal Belda; Ignacio Casal; Fernando Corrales; Concha Gil; Adolfo Lopez-Munain; Jesus Prieto; Jesus Rodriguez-Padial; Fernando Vivanco; Francisco J Blanco . Spanish B/D-HPP Consortium, A Coruña, Spain. • RE:  Abstract log #217 Your abstract entitled  Automatic reporting and reproducibility analysis of ProteoRed participants in the multi-laboratory studies using  the “MIAPE extractor” tool (log #217) is formally accepted for poster presentation at the HUPO 11th Annual World Congress, September 9-13, 2012 in Boston, MA (USA).  • RE: Abstract log# 785 Your abstract entitledReporting and connecting experimental information through proteomics data standards.J. Alberto Medina-Aunon; Salvador Martínez de Bartolomé; Miguel A. López; Juan P. Albar Centro Nacional de Biotecnología - CSIC, Madrid, Spainfor the HUPO2012 conference was submitted on 7/11/2012.

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