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Appendix 2

The Annual C-HPP Report to HUPO Council (7/31/2017): Approved by C-HPP EC Members

The C-HPP Activity Report for 2017 HUPO Council

Date: August 1, 2017

1. Name of committee: Chromosome-Centric Human Proteome Project (C-HPP) Consortium
   
   
2. Name of committee chair: Chair: Young-Ki Paik, Co-chairs: Lydie Lane, Christopher M Overall
   
   
3. Names of committee members: including new members and members that rotated off this year
   C-HPP Executive Committee Members and Principal Investigators Council Members (see Appendix 1)
   
   
4. C-HPP Mission and Objectives (latest updated: August 1, 2017)
   The mission of the C-HPP is to map and annotate the entire human protein set encoded by each chromosome. The initial steps of the project are focused on the so called “missing proteins” (MPs), which lacked documented evidence for existence at protein level. At present, there remain 2,579 MPs (neXtProt 2017-01-23). Also targeted are alternative splice isoforms and post-translational modifications (phosphorylations, glycosylations, acetylations), small open reading frame ORF translation products (smORFs) and long non-coding (lnc) RNAs.
   
   
5. Summary of recent accomplishments, current activities, tasks (see C-HPP Newsletter No. 6, 2017)
   A. Major Accomplishment: Since the C-HPP was launched in 2012 with a 10-year perspective, it has made substantial progress during Phase I (2012 to 2018). As summarized in Fig. 1, the C-HPP group has established some milestones in six areas of cooperation with the bioinformatics teams and individual investigators. The areas of cooperation are: (i) the “Metrics” system for updating the yearly progress in protein annotation, (ii) the PDX data submission rule, which was a first step toward to community-wide data sharing, (iii) the MS data interpretation guidelines 2.1, (iv) data managing bioinformatics tools, (v) collaboration systems with the JPR special issue publications, and (vi) rare sample utilizations for MP detection. These accomplishments of the C-HPP would have been impossible without community-wide support and cooperation. They should have a full credit for this accomplishment.
   
   
   
   Fig. 1. Major accomplishments of C-HPP via an interactive cooperation of both HUPO HPP groups and non-HUPO proteomics community
   
   
   B. Summary of 15th C-HPP Workshop in Taipei and Sun Moon Lake, Taiwan
   
   Overview of HPP Activity: HPP’s Annual General Investigators Meeting was held on Sunday morning (September 18). C-HPP and B/D-HPP investigators gathered to discuss HPP progress and future. This overview was followed by presentations by chairs of the HUPO Technology Pillars: Eric Deutsch for Bioinformatics, Emma Lundberg for Antibodies, and Susan Weintraub for MS, who provided an update on the HPP guidelines for MS data handling and activity.
   
   Invited Talks: The highlights of the morning session were lectures by Mike Snyder (Chair, SSAB of HPP, Stanford University, USA) and Alan Saghatelian (Salk Institute, San Diego, USA). These two talks informed us about conceptual advances in the scientific direction of HPP research and also provided new guidance on how we can more completely achieve our C-HPP goals and human proteome annotations. First, Mike addressed the essential roles of RNA Seq for Proteogenomics-based HPP studies with respect to the identification of new isoforms (splice junction mapping, synthetic long reads). He also introduced the use of barcodes for sequence variants (e.g., PacBio System) and GTEx Project. Second, Alan addressed the incorporation of microproteins (or small ORF encoding proteins, SEPs) into ongoing C-HPP activities. This would involve seeking ways to incorporate microproteins (or short ORF-encoding peptides; SEPs, <150 AA) and adopting general strategies for identifying SEPs. Some examples were introduced (so-called “Nobody” proteins) with their cellular localization and functional aspect by using shRNA K.D.
   
   C-HPP Working Group Session: C-HPP consortium held a discussion session on three topics: recapturing the concept of HPP cluster grouping (by Paik), the direction of next-50 challenge (by Overall), and progress in the annotation of missing proteins at neXtProt portal (by Lane). In addition, several C-HPP PIs, including Chr 3 (T. Nishimura), 15 (G. Domont), 18 (Archakov), 22 (MS Kim), and Y (Salekdeh) showcased their progress on the missing protein hunt and related scientific work.
   
   Joint Cluster Group meeting: The first Cancer Cluster Group Meeting involved more than 45 attendees. In this session, several guest speakers including Phil Robinson (ProCan), Jerry Lee (NCI Office), and Henry Rodriguez briefly introduced the “Moon Shot project” shared by Australia and the USA and its effect on international cancer proteomics research. Follow-up open discussions on the vision of cancer projects and related topics were held by those panels, especially Mark Baker, Hui Zhang, Chris Kinsinger (CPTAC), and Jacob Kagan (EDRN). Two additional cluster group meetings (the IVTT Cluster Group led by Gyorgy Marko-Varga and the Reproductive disease cluster led by Charles Pineau and Hosseini Salekdeh) were held separately. The next morning, the Membrane proteome (led by Daniel Figeys) and Neurodegenerative disease cluster groups held their own discussions. The latter meeting (led by Jong Shin Yoo and Andrea Urbani) was jointly held by HBPP (B/D-HPP) and the neuro-disease group (C-HPP), and the participants shared many views on resources, methods, and database construction.
   
   
   
   
   C-HPP PIC members at Sun Moon Lake, Sept 22, 2016
   
   
   C. Summary of 16th C-HPP Workshop in Rio de Janeiro, Brazil (December 10th – 12nd) Organized by Gilberto B. Domont, Brazil
   The 16^th C-HPP workshop was held in Rio de Janeiro, Brazil between 10 to 12 December 2016, in conjunction with the Centennial Anniversary of the Brazilian Academy of Sciences with message of “Translating the code of life into proteins and diseases”. The meeting was opened Saturday December 10 by Pedro Vasconcelos representing the Brazilian Academy of Sciences, Marcelo Valle de Sousa, President of the Brazilian Society of Proteomics, Marcos Eberlin, president of the Brazilian Society of Mass Spectrometry and Mark Baker, HUPO President and highlighted with Dr. Vasconcelos’s Keynote lecture on Zika virus epidemics. Sunday December 11, Catherine Costello presented the progress in the assignment of glycosylation which was followed by lectures of Manuel Fuentes, Fernando Corrales, Peter Horvatovich, Fabio Gozzo, Garry Corthals, Christoph Borchers, Daniel Martins de Souza and Peter Nilsson on various C-HPP and disease topics. The workshop followed with a common section with the 1st Ibero-American Conference on Mass Spectrometry where the keynote speaker was Alexander Makarov, the inventor or Orbitrap mass analyser. Monday 12th December, the workshop host Gilberto B. Domont, Organizer, led a debate on the assessment and evaluation of the publication of the first HUPO Human Proteome Map which was followed by discussion on the role of proteomics for personal and translational medicine by Gyorgy Marko-Varga and Johan Malm as summarized at C-HPP Wiki. (see C-HPP Newsletter No.6)
   
   
   
   
   Participants of 16^th C-HPP Workshop in Rio de Janeiro, Brazil
   
   
   D. Summary of 17th C-HPP Workshop in Tehran, Iran, April 27/28, 2017 Organized by Ghasem Hosseini Salekdeh, Iran
   
   17^th C-HPP symposium/workshop was held in Tehran, Iran, April 27th – 28th 2017 with the contribution of the leadership and well-known scientists from all over the globe. The participants shared their last findings on the progress of C-HPP concerning each individual chromosome and very recent approaches to overcome the challenges facing missing proteins discovery. More than 300 hundred Iranian scientists, researchers and students attended this symposium (Figure 1). In this meeting, in addition to ongoing efforts, the prospective programs to maintain collaborative works, share resources and information and formation of a newly organized working group termed TAMPA were discussed. Following the welcome words of Dr. Gourabi, Head of Royan Institute and Dr. Hosseini Salekdeh, Symposium Chairman, this was proceeded with several scientific sessions and open discussion: Introduction and Overview, Uncovering Missing Proteins, Functional Study of Missing Proteins with Disease Implication, Invited Special Lectures, Young Investigator Invitation Session, General Discussion on All Pending Issues, and Working Group Formation: Networking and Interaction through the C-HPP Clusters. We thank Ghasem Hosseini Salekdeh (PI of Chr Y) and his staffs for their excellent hospitality during and after the meeting. At the 2^nd day
   
   
   
   
   Participants of 17^th C-HPP Symposium/Workshop in Tehran, Iran (4/27-28, 2017)
   
   
   It should also be noted here that Dr. Gil Omenn joined this session through Skype from his home (at early 2-3 AM in Michigan Time) and gave us many constructive suggestions and simulative comments on every issue. A detailed report on his views and suggestions will be reported in the upcoming C-HPP Newsletter. All of the participants thanked him for his dedication to this productive discussion session, one of the most vibrant forums via tele-video mediation as HPP chair.
   
   E. Information sharing through C-HPP Wiki
   C-HPP Wiki is an online platform to share information on individual and collaborative activities of C-HPP Chromosome teams and associated groups. C-HPP Wiki specifies C-HPP community guidelines and resources available within collaborative groups, and has a sections to inform members and followers on important news and events. The scientific program of all C-HPP related workshops and meetings is listed (http://c-hpp.web.rug.nl/tiki-index.php?page=General%20meeting) including slides of many presentations offered by presenters making accessible the content of presentations to outside world. This Wiki has been a key archive for all C-HPP activity since 2012.
   
   
6. List of activities in progress, milestones, upcoming events:
   
   A. Journal of Proteome Research SI (to be published on Nov or Dec 2017)
   
   Continuing our scientific endeavors toward missing proteins annotation, we now have received more than two dozen of manuscripts as of July 31st. The contents in this JPR SI (Associate Editor, Chris Overall) will include more in-depth studies of missing proteins, biology, diseases, and technology developments. At present, >20 manuscripts have been reviewed and revised, mostly focusing on the C-HPP subjects, and currently finalizing the review process toward publication around the end of 2017. As papers are accepted they will go online and so most will be available in time for HUPO-2017 in Dublin. Due to the publication schedule, only papers that are accepted by September 1, 2017 will be published in this December 2017 HPP Special Issue. Papers requiring more time for revision will be considered for later regular issues. We may be able to generate a JPR Virtual Issue early 2018 in consultation with the EIC for all HPP related papers that appeared since the last SI that were not in a SI.
   
   B. Working Group Formation of C-HPP
   As the HUPO and HPP leadership have suggested that annotation work on the missing proteins (MPs) should be expedited, the C-HPP leadership has been working on a major reorganization of the current C-HPP Consortium focus and so designated the active working group modules in three teams. The current C-HPP consortium will continue to run, and the working groups are more focused on special missions as key players in the neXT-50 campaign (e.g., MP search, annotation, and functional study). Details on this move will be discussed in Dublin HUPO Congress.
   
   
   
   
   
   In this structure, the MP annotation team mainly comprises those involved in the neXt-50 challenge campaign led by Dr. Chris Overall, whereas the MP bioinformatics team mainly comprises those involved in the public DB maintenance or related bioinformatics services in each Red and Blue team. This MP bioinformatics team is led by Dr. Lydie Lane. Lastly, the MP functional study team would focus more on the characterization of the MPs using various cell lines, rare tissues (e.g., nasal epithelium over the cribriform plate for ORs, IVTT tech, membranes and model organisms. This MP functional study team is led by Young-Ki Paik. The reorganized teamwork should be an ideal working model to shorten the time from discovery, annotation and functional characterization to translational proteome biology. The shortened research time will move molecular dynamics from genome to proteome and comprehensive approaches to disease mechanisms from cancers to preeclampsia and neural disease.
   
   
7. Future goals, vision of committee
   Given that the highest priority was initially placed on MP annotation in the newly structured teams, the neXt-50 challenge campaign led by Dr. Chris Overall, the MP bioinformatics team led by Dr. Lydie Lane and the MP functional study team led by Dr. Young-Ki Paik will put their efforts to shorten the time from discovery, annotation and functional characterization to translational proteome biology. This restructured C-HPP teams will move molecular dynamics from genome to proteome and comprehensive approaches to disease mechanisms from cancers to preeclampsia and neural disease in the future. It is also necessary to find a better way of enhancing our research capability and the deliverables of the C-HPP teams. For example, studies of families of proteins, PTMs and protein proteoforms will be good targets for the project which shall be useful for discovery of diagnostic biomarkers or molecular therapeutic targets in the future.
   
   
8. Financial impacts and/or requests (if appropriate)
   
   
9. Recommendations to the HUPO Council and Executive Committee
   
   As the central activity of C-HPP for the past 5 years has been supported by the Korean Government funds (to YKP), it becomes now important that HUPO HQ and EC may write a letter of support for C-HPP activity including each national team’s efforts and send it to the corresponding national Granting Agency in their host countries. This will greatly help each Chr team to promote its scientific activity on own chromosome.

Click here to go the overview of C-HPP activities in HUPO 2017, Dublin.