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Chris Overall, C-HPP Chair, Canada
The Human Proteome Project (HPP) 8th Special Issue in the Journal of Proteome Research was published on December 4, 2020, with more 15 articles and one editorial addressing different issues related to the human proteome. This is issue is celebrating progress on establishing the existence at the protein level of 90% of the human protein coding genes. The Guest Editorial team comprising Drs. Young-Ki Paik, Gil Omenn, Lydie Lane, Eric Deutsch, Fernando Corrales, and Chris Overall (Associate Editor) were responsible for this 8th Special Issue. The whole issue is available at the Journal of Proteome Research website.
New neXtProt release with new human protein features
The neXtProt team is happy to announce release 2020-11-26 and that features updated protein-protein interaction data from IntAct and updated expression data from Bgee. Bgee is a database to retrieve and compare gene expression patterns in multiple animal species ,which is also developed at the SIB Swiss Institute of Bioinformatics (Nucleic Acids Res. 2020 Oct 10:gkaa793. doi: 10.1093/nar/gkaa793).
For more information, please see: https://www.nextprot.org/news/new-release-with-updated-expression-and-interaction-data.
The next important release of neStProt with updated proteomics data is planned for February 2021 on which the C-HPP teams can measure their progress in completion of the human proteome.
Join us! Research teams for Chromosome 21 and 22!
C-HPP Consortium leadership is looking for partners to can join the C-HPP initiative to advance neXt-MP50 and neXt-CP50 projects by identifying missing proteins and identify function(s) to uPE1 proteins for chromosomes 21 and 22. Motivated PIs are encouraged to contact Chris Overall (Chair of C-HPP, email email@example.com) or other members of the C-HPP leadership.
We wish you and your family Happy New Year for 2021 and we hope that vaccination against SARS-CoV2 will allow our scientific community and others to meet each other again in person on international meetings, workshops and conferences.
Cristina Ruiz-Romero, Grupo de Investigación de Reumatología (GIR), Plataforma de Proteomica-PROTEORED-ISCIII, INIBIC - Complejo Hospitalario Universitario de A Coruña and Francisco J Blanco, Grupo de Investigación de Reumatología y Salud (GIR-S), Departamento de Fisioterapia, Medicina y Ciencias Biomedicas. Universidad de A Coruña
One of the priorities of translational proteomics is to facilitate the development of precision medicine strategies. These involve a deeper knowledge on the molecular profiles of diseases and patients, improving prediction and prevention and promoting a more personalized and participative medicine. In this field, the HPP initiative on Rheumatic and Autoimmune diseases (RAD-HPP) has focused on the application of proteomics for the development of predictive models for precision medicine. These models would enable the identification of disease phenotypes and the stratification of patients according to their future response to treatment.
In patients with osteoarthritis (OA), the Rheumatology Research Group in A Coruña (http://girblanco.com) has recently developed a kit, named DITOBA, for its diagnosis on the basis of the measurement of four proteins in serum. These proteins were identified in previous proteomic analyses performed by the group on samples from the Prospective Cohort of OA A Coruña (PROCOAC, Spain). A first LC-MS/MS analysis identified eleven peptides associated with OA and subsequently a targeted luminex-based assay was developed to quantify the corresponding proteins in 400 samples from PROCOAC. The inclusion of these proteins into a clinical model composed of demographic and clinical data has resulted in an algorithm for the diagnosis of OA without the need of XRay. Furthermore, a clinical validation of this model has been carried out in 1200 samples from the Osteoarthritis Initiative Cohort (OAI, USA) to qualify its use to monitor disease severity in OA positive cases, and predict the incidence of the disease before 8 years in the negative ones. This kit will facilitate the personalized management of patients suffering OA.
Regarding rheumatoid arthritis (RA), a collaboration between RAD-HPP members has identified a specific autoantibody (anti-CENPF) whose presence in serum is associated with a positive response of the patient to Infliximab (a TNF inhibitor). In this case, the screening was performed on a cohort from Santiago de Compostela (Spain) using planar antigen arrays from the Human Protein Atlas, which contain 42100 PrEST representing 19000 unique proteins. Further targeted validations were carried out on additional samples from A Coruña (Spain) and Sweden (SWEFOT cohort), in this case using in-house made suspension beads arrays. Finally, a statistical analysis was performed to assess the clinical relevance of the findings. The addition of anti-CENPF antibodies to demographic and clinical variables (age, sex and a disease activity score) resulted in the best model to predict responders to Infliximab, showing an area under the curve (AUC) of 0.756 (Lourido et al., Seminars Arthritis Rheum 2020). This study indicates the usefulness of anti-CENPF measurement to guide therapeutic interventions in RA.
Finally, RAD-HPP members have also focused interest on the analysis of the RA citrullinome and its link to clinical phenotypes (Fert-Bober et al., Immunol Rev 2020), and others have participated through the Accelerating Medicines Partnership in RA/SLE Consortium in a ground-breaking work providing a molecular basis by which stromal cells can be therapeutically targeted in RA (Wei et al., Nature 2020). Altogether, these studies show the latest activity of RAD-HPP in the development of initiatives for the application of proteomics strategies to improve the management of patients suffering RAD.
The Human Proteome Project (HPP) Special Issue in Journal of Proteome Research will be published on December 4, 2020, with more 15 articles and one editorial addressing different issues related to the human proteome. The Guest Editorial team comprising Drs. Young-Ki Paik, Gil Omenn, Lydie Lane, Eric Deutsch, Fernando Corrales, and Chris Overall (Associate Editor) were responsible for this 8th Special Issue.
- The Special Issue commences with the Annual HPP Metrics paper by Omenn et al 2020 (https://doi.org/10.1021/acs.jproteome.0c00485). The HPP metrics paper provides fine grain detail of progress and challenges in credibly identifying the human proteome over the past year.
- Two papers addressing the use of pluripotent stem cells (PSCs) to study function of uPE1 proteins, which proteins are well detected, but they have no single known molecular function by Frederik Edfors and Ghasem Salekdeh and colleagues (https://dx.doi.org/10.1021/acs.jproteome.0c00689).
- Kotol et al (https://dx.doi.org/10.1021/acs.jproteome.0c00194) used information derived from the Human Protein Atlas to devise a series of isotopically labelled peptides with corresponding PRM assays for the detection of 21 drug targets and biomarkers in human plasma.
- Insight into the First Phosphoproteomics challenge of the MS Resource Pillar by Rob Moritz and Sue Weintraub in Hoopmann et al (https://dx.doi.org/10.1021/acs.jproteome.0c00648). Standardised sets of 94 phosphopeptides were analysed by 22 laboratories using different approaches, MS instrumentation and bioinformatics. The data were reanalysed in a consistent manner that pointed out the challenges of correct phosphopeptide site identification.
- Bioinformatics approaches were developed as described in this special issue to tackle the uPE1 challenge include a guilt-by-association bioinformatics approach from the Spanish team in Gonzalez-Gomariz et al 2020 (https://dx.doi.org/10.1021/acs.jproteome.0c00364). In an innovative approach, the authors employed web search tools, such as the Google page rank algorithm, to develop UPEFinder. The Korean Chromosome 11 team used the successful I-TASSER/COFACTOR approach to predict 2,413 GO terms for 22 uPE1 chromosome 11 proteins (https://dx.doi.org/10.1021/acs.jproteome.0c00482).
- Ping Xu team used Open-pFind tool, which is an open modification search tool, which improves identification of peptide and proteins, and with this tool the authors identified peptides candidates for 103 missing proteins, from which 4 were validated in the study (https://doi.org/10.1021/acs.jproteome.0c00370) (China).
- From the Human Protein Atlas and the Antibody Resource Pillar comes the achievement of “enhanced validation” of nearly 6,000 antibodies directed towards 3,775 proteins in many tissues detailed by Sivertsson et al (https://dx.doi.org/10.1021/acs.jproteome.0c00486) (Sweden). This led to the localization of 56 candidate MPs and 171 uncharacterised PE1 proteins (uPE1) lacking any known function.
- Vandenbrouck et al 2020 (https://dx.doi.org/10.1021/acs.jproteome.0c00516) tackled the uPE1 neXt-CP50 Challenge in a cohort of 421 uPE1 proteins found in higher abundance in the male reproductive tract by compilation of diverse evidence. To functionally annotate such proteins, contextual information from the literature, protein-protein interactions, expression levels and cellular localization were employed in a knowledge-driven approach to suggest rational, knowledge-founded hypotheses that can be experimentally tested in a targeted manner with higher probability of incise results and less false starts.
- The Journal welcomes the new Chair of the HPP, Dr. Rob Moritz, Institute for Systems Biology, Seattle as a new Guest Editor for the 9th Annual Special Issue of the Journal of Proteome Research on the HPP in 2021.
C-HPP Consortium leadership is looking for partners, which can join C-HPP initiative to advance MP50 and CP50 projects by identifying missing proteins and identify function(s) to uPE1 proteins for chromosomes 21 and 22. Motivated PIs are encouraged to contact Chris Overall (Chair of C-HPP, email firstname.lastname@example.org) or other members of the C-HPP leadership.
23rd C-HPP Workshop in Busan (South-Korea), June 28-30, 2021
Due to COVID-19 pandemic and related health risk and world-wide travel restrictions we had many meetings and workshops cancelled, amongst others the 23rd C-HPP Workshop originally planned in May 15-18, 2020 in Saint Petersburg, Russia. We hope that vaccine against SARS-CoV-2 viral infection will be available in early next year and our onsite meeting will be held in Summer 2021 as planned. Therefore, we would like to encourage you to plan on joining the 23rd C-HPP Workshop on June 28-30, 2021, in Busan, South Korea. This meeting is being organized in conjunction with Commemoration of the 20th Anniversary of AOHUPO (www.aohupo.org). The C-HPP EC will make you update on the preparation of this meeting with scientific programs through the websites of HUPO, C-HPP and C-HPP Wiki in addition to our routine email communications.
We wish you and your family to stay safe and healthy.
Bruno Tilocca and Paola Roncada, HUPO B/D-HPP Food and Nutrition Team, University Magna Græcia of Catanzaro, Catanzaro, Italy
The animal gastrointestinal tract provides the perfect milieu for hosting the heterogeneous ensemble of microorganisms (bacteria, virus, fungi and protozoa) that are commonly harbored in the intestine. Here, microbiota members establish a complex and intricate network of interconnections among each other and the hosting organism. Recent investigations unveiled the importance of understanding the synergistic interactions between the host and its microbiota, enlightening how the fine orchestration of the gut microbiota composition and activity impact a variety of biochemical and physiological processes that are, in turn, responsible for both beneficial and detrimental health conditions in humans and animals. In this context, Dr. Bruno Tilocca along with the other researchers of the “Feed-gut-microbiota” group of the University of Hohenheim employed a microbial community fingerprint through 16S rRNA gene sequencing and metaproteomics to study the active bacterial fraction inhabiting the diverse sections of the chicken and pig gastrointestinal tract. Investigating the microbiota by the sole genome-targeting approaches enables a comprehensive depiction of the microbial consortia architecture and its potential functions as assessed through the functional prediction of the sequenced genetic elements. Nevertheless, structural composition assessed by microbial community fingerprint has been leveraged by Dr. Tilocca and colleagues while optimizing a metaproteomic workflow aimed at the effective functional featuring of the microbial community harbouring the diverse intestine sections. Specifically, the bacterial families identified by the 16S rRNA gene sequencing are employed for the construction of a single non-redundant in-house database. The database dependent searches performed by the custom databases resulted in a higher protein identification rate as compared with the conventional metaproteomics workflow expecting bioinformatic searches against publicly available databases. Also, the use of DNA-driven custom database enabled a statistically confident identification of the protein dataset and its successive functional classification. Through metaproteomics Dr. Tilocca and colleagues gained a fair depiction of the metabolically active bacterial fraction, allowing for the elucidation of the core microbiota composition along with the major biochemical pathways the gut microbiota members of the diverse gastrointestinal tract sections are involved in. Marked differences were observed in the microbial communities of the diverse gastrointestinal tract sections in both structural and functional terms. Both chicken and porcine animal model reported increased microbial diversity when moving toward the caudal direction. Interestingly, discrepancies were observed when comparing the microbiota architecture assessed by the DNA-based method and the metaproteomics. The higher bacteria heterogeneity highlighted by the metaproteomics has been attributed to the changing microbiota dynamics and the fact that changes in protein abundance occur earlier than changes of DNA copy numbers. This observation provides support in the identification of metaproteomics as a suitable discipline for the investigation of the microbial community composition in dynamic contexts, representing a valuable tool to highlight the microbial specimens driving the changes required to the achievement of a novel homeostatic balance. Besides, functional featuring of the microbiota in the diverse gastrointestinal sections through metaproteomics enabled deciphering biochemical involvement of the bacterial families in the diverse sections other than clarify the contribution of the microbiota in the animal physiological processes and the response to external stimuli such as the reaction to environmental stressors
More recently, research interests of the Dr. Tilocca are extended to the study of the microbial communities inhabiting “abiotic” ecological niches such as the milk and its by-product. In this view, Dr. Tilocca along with the Prof. Paola Roncada, at the Department of Health Science of the University “Magna Graecia” of Catanzaro, are running an articulated research project aimed at featuring the Nicastrese raw milk, and cheese. Here, metaproteomics is the method of choice as it enables the demonstration the microbiological signature (i.e. the active bacterial fraction) of the raw milk of this typical Calabrian goat bred and describes the structural and functional shaping of the microbiota throughout the diverse cheese-making steps. Besides, metaproteomics allows for detailing the biochemical role of the microbiota in ensuring both biosafety and the development of the unique gustatory and olfactory essences of this traditional product. In this view, researchers are confident that employing such innovative approach might open new avenues for the fair valorization of this and other ancient and typical products with unevaluable benefits for the social and economic reality at a local level other than delighting the palate of the consumers, worldwide.
Dr. Bruno Tilocca is currently Assistant Professor at the University “Magna Graecia” of Catanzaro in the field of proteomics, microbiology applied on animal infectious disease in prof. Paola Roncada’ s group. He gained a PhD at the University of Hohenheim (Germany) in animal science. His research activities concern the animal infectious disease and the study of the animal microbiota through omics sciences. His research works are summarized in over 20 peer-reviewed articles and two contributes to books.
With the expanding goals of the HPP and aggressive timelines to drive the numerous initiatives under the HPP umbrella of activities, the HPP seek to engage a vibrant, well-organized, and goal-oriented proteomics researcher to the HPP Co-Chair position to support and assist the HPP Chair.
The HPP Co-Chair position is a 2-year term and will commence January 2021.
To apply, please submit a brief (<1 page) vision statement outlining why you are a suitable candidate for this position. Email vision statement to email@example.com before November 30, 2020.
Since the COVID-19 pandemic and related health risk world-wide poised travel restrictions, the C-HPP 23rd C-HPP Workshop in Russia was canceled. We hope that vaccine against SARS-CoV-2 viral infection will be available, which would ease travel restrictions by summer 2021. If so we hope our PIC members and all interested C-HPP members will join the next C-HPP Workshop to be held on June 28 – 30, 2021 in Busan, South Korea. The C-HPP EC will announce in due time the program on the HUPO, C-HPP Portal and C-HPP Wiki websites.
(C-)HPP achievement on completion of 90% of the Human Proteome with high stringency
C-HPP related program and highlights are available at C-HPP Wiki. The C-HPP EC wish you and for all your family to stay safe and healthy.
The C-HPP PIC meeting at HUPO Connect 2020 was held on Monday, October 19, 17:15 – 18:10 EST time where the following topics were discussed and some important decisions were made:
In the midst of a pandemic, in the midst of the global effort to develop effective vaccines and anti-virals for SARS-CoV-2—yet, paradoxically, also in the midst of a surreal moment in history where the very science that can save millions is assailed if the facts and truth conflict with political mantra—we nonetheless can celebrate. Reminding us all of the importance and relevance of science, today, October 19, 2020, we celebrate the announcement of the draft human proteome in the opening talk at HUPO CONNECT by the First Chair of the Human Proteome Project (HPP), Dr Gil Omenn, with a virtual issue of the Journal of Proteome Research (https://pubs.acs.org/page/jprobs/vi/humanproteome). In the virtual issue the editors have compiled 60 of the most significant papers published in the Journal over the past decade on the human proteome project reflecting the diversity of the C-HPP and B/D-HPP teams, regions, approaches, impact and achievement.
The neXtProt database posted the landmark human proteome data release covering 90% of the human proteome on 17th January, 20201, which is now reported by the HPP Consortium in Nature Communications by Adhikari et al 20202. In the companion annual human proteome metrics paper by Gil Omenn et al 20203 reporting this year’s progress of the HPP, the underlying data is presented in depth. The metrics paper will be published in the 8th Special Issue of the Journal of Proteome Research dedicated to the HPP in December 2020, with the ASAP preprint online today leading this HPP Virtual Issue and with a commentary editorial by Chris Overall4.
The human proteome was identified by HPP global research teams and scientists from the wider scientific community and assembled by the Chromosome Centric-HPP (C-HPP) and the HPP Knowledgebase Pillar data curators from neXtProt PeptideAtlas, and MassIVE. The C-HPP was established in 2010 as the major initiative of the HPP to identify at least one protein form (proteoform) from each of the protein-encoding genes in the human genome. For the next high-fidelity compendium of the full human proteome and to develop a broader understanding of life, human conscience, and disease, proteomics needs more data, more patients, more scientists, and more doctors to understand life, individuality, personality and disease—science needs us all, but now, more than ever, humanity needs more science
2. Subash Adhikari, Edouard Nice, Eric Deutsch, Lydie Lane, Gilbert Omenn, Steve Pennington, Young-ki Paik, Christopher Overall, Fernando Corrales, Ileana Cristea, Jennifer Van Eyk, Mathias Uhlen, Cecilia Lindskog, Daniel Chan, Amos Bairoch, James Waddington, Joshua Justice, Joshua LaBaer, Henry Rodriguez, Fuchu He, Markus Kostrzewa, Peipei Ping, Rebekah Gundry, Peter Stewart, Sanjeeva Srivastava, Sudhir Srivastava, Fabio Nogueira, Gilberto Domont, Yves Vandenbrouck, Maggie Lam, Sara Wennersten, Juan Antonio Vizcaino, Marc Wilkins, Jochen Schwenk, Emma Lundberg, Nuno Bandeira, György Marko-Varga, Susan Weintraub, Charles Pineau, Ulrike Kusebauch, Robert Moritz, Seong Beom Ahn, Magnas Palmblad, Michael Snyder, Ruedi Aebersold, and Mark Baker. A High-Stringency Blueprint of the Human Proteome, Nat. Communications, 2020, doi.org/10.1038/s41467-020-19045-9.
3. Omenn G. S.; Lane L.; Overall C. M.; Cristea I. M.; Corrales F. J.; Lindskog C.; Paik Y-K.; Van Eyk J. E.; Liu S.; Pennington S.; Snyder M.P.; Baker M.; Bandeira N.; Aebersold, R.; Moritz, R.L.; Deutsch EW. Research on The Human Proteome Reaches a Major Milestone: >90% of Predicted Human Proteins Now Credibly Detected, According to the HUPO Human Proteome Project. J Proteome Res. 2020, Sep 15. doi: 10.1021/acs.jproteome.0c00485.
4. Overall, C.M. J Proteome Res. 2020, October 19. The HUPO High-Stringency Inventory of Humanity’s Shared Human Proteome Revealed. https://pubs.acs.org/doi/full/10.1021/acs.jproteome.0c00794.
In June 2020, the inaugural Chair of the HUPO Pathology Pillar, Prof. Dan Chan (Johns Hopkins University) decided to step down because of his large additional workload due to the Covid-19 pandemic. A new appointment protocol was established in order to find a suitable replacement. Applications were sought by advertising through HUPO and reaching out to possible candidates. Applicants were required to apply in writing addressing the following key points:
i) Proteomics track record
ii) HUPO/HPP track record
iii) Evidence of national and International visibility
iv) Vision for the future development of the Pathology Platform
v) A one page CV
vi) The names of high-profile scientific/clinical referees
A committee consisting of 5 senior HUPO scientists was established to review the applications and a recommendation made to the chair of the HPP to take to the HUPO EC and Council for endorsement.
We are pleased to announce Prof. Michael Roehrl (Memorial Sloan Kettering Cancer Center, New York (MSKCC)) as the new Chair of the HUPO Pathology Pillar. Michael is a practicing physician-scientist who holds an MD from Munich, Germany, and a PhD from Harvard in Biological Chemistry. He trained at Harvard Medical School and Massachusetts General Hospital and is US board-certified in both Anatomic Pathology and Laboratory Medicine. He directs the Center for Precision Pathology at MSKCC, and his clinical practice is focused on gastrointestinal oncologic pathology. Michael runs a research lab that studies the biology of solid tumors, and his group uses proteomics and protein-based biomarkers extensively with the goal of creating next generation diagnostics and theranostics for the benefit of cancer patients.
The Pathology Pillar was launched at the 17th HUPO World Congress in Orlando in 2018 based on the realization that pathology (and clinical patient-focused applications) will play a key role in the clinical translation of proteomics methods and data and its use in precision medicine. The goals of the Pathology Pillar are to coordinate the identification of key unmet needs in clinical medicine, stimulate guidelines and standards for the development of fit-for-purpose validated clinical assays, promote awareness of best practice and coordinate access to high quality clinical samples and their associated data. The Pillar also aims to promote partnerships with key international pathology organizations, diagnostic industries, and regulatory agencies, develop educational programs and support early career researchers.
With Michael at the helm, the HPP Pathology Pillar has a bright future and is requesting members to get involved and help drive this initiative. The integration of the other HPP Pillars to provide information and resources to the pathology Pillar will ultimately propel proteomics efforts further into the clinic and benefit health and wellbeing of all.
Michael is honored to have been elected new Chair and, together with Co-Chair Ed Nice, is very much looking forward to engaging the entire HUPO community!
Please contact Michael at firstname.lastname@example.org and find his lab on Twitter @Roehrl_Lab
The 2020 Metrics of the HUPO Human Proteome Project (HPP) effort to credibly detect every protein of the human proteome has been released (see https://pubs.acs.org/doi/10.1021/acs.jproteome.0c00485). This report now provides evidence for detected expression for >90% of the 19,773 predicted proteins coded in the human genome. The HPP annually reports on the progress made throughout the world toward credibly identifying and characterizing the complete human protein parts list and promoting proteomics as an integral part of multiomics studies in medicine and the life sciences. The 2020 metrics paper describes the credibly detected proteins (PE1 level) as well as the 4 other PE levels of protein evidence in a central repository for community sharing of these results. With the neXtProt release of 2020−01, 17,874 genes encoding proteins are classified as PE1 and having strong protein-level evidence. This PE1 level is up 180 proteins from 17,694 one year earlier and represent 90.4% of the 19,773 predicted coding genes (all PE1,2,3,4 proteins in neXtProt). Conversely, the number of neXtProt PE2,3,4 proteins, termed the “missing proteins” (MPs), was reduced by 230 from 2129 to 1899 since the previous year’s release neXtProt 2019−01. PeptideAtlas is the primary source of uniform reanalysis of raw mass spectrometry (MS) data for neXtProt, supplemented this year with extensive data from the MS repository MassIVE. The mass spectrometry data knowledge bases promoted 362 and 84 canonical proteins (PeptideAtlas and MassIVE respectively) in the last year to increase the credibly identified proteins. The Human Protein Atlas also released new protein detection repositories (based on antibody binding data to human proteins) for Blood, Brain, and Metabolic Atlases. The Biology and Disease-driven (B/D)-HPP teams continue to pursue the identification of driver proteins that underlie disease states, the characterization of regulatory mechanisms controlling the functions of these proteins, their proteoforms, and their interactions.
Of the remaining “missing proteins”, hydrophobic proteins account for about 40% of these and are compounded by protein sequence structures that are difficult to extract credible peptides for high-stringency identification. These missing proteins include large families or groups including GPCR, zinc finger, homeobox, keratin-associated, and coiled-coil domain proteins. We expect novel strategies for finding missing proteins, characterizing the functions of already-detected “dark” proteins, and utilizing proteogenomics in precision medicine to be fruitful in the coming years.
In addition, the Journal of Proteome Research will produce a year-end virtual Issue with dozens of high-impact papers from the 7 annual special issues of JPR from the Human Proteome Project.
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