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Cora N. Betsinger and Ileana M. Cristea, Princeton University, Department of Molecular Biology, Princeton, New Jersey, USA
A mission of the HUPO Biology/Disease-driven Human Proteome Project (B/D-HPP) is to explore how the human proteome can provide a lens for understanding human disease. The Human Infectious Diseases team (HID-HPP) of the B/D-HPP, is specifically devoted to the study of human diseases caused by infectious pathogens (https://www.hupo.org/Infectious-Disease-Initiative). One objective of HID-HPP is to develop, make broadly available, and apply proteomic methods to understand the biology and pathogenicity of viruses. For example, members of the HID-HPP have applied a range of proteomic methods to define alterations in the cellular proteome, protein interactome, and protein posttranslational modifications during infection with diverse viral pathogens1, such as herpesviruses and influenza A2–6. Given the ongoing global pandemic derived from infection with the novel SARS-CoV-2 virus7, here we highlight the demonstrated and promised power of proteomics to provide urgently needed insight into the biology and pathogenicity of this coronavirus and to uncover therapeutic targets.
Upon the emergence of a new viral pathogen in the human population, some of the first steps undertaken are to isolate the virus from patient samples and sequence the viral genome. This is critical for the taxonomic classification of the virus, determination of its phylogenetic relationship to other viruses, and identification of zoonotic host species. However, genetic analysis cannot fully address many aspects of virus biology, including the identity and function of virus proteins, how the virus interacts with host cells during its entry and replication, and what changes infection elicits at the cell and system level. Over the past twenty years, three of the emergent viruses that have resulted in widespread human disease and fatality have been members of the Coronaviridae family. SARS-CoV was identified as the causative agent of the 2003 severe acute respiratory syndrome (SARS) outbreak, which had a fatality rate of 10%8. MERS-CoV emerged ten years later, in 2013, and had a case fatality rate of more than 30%8. The most recent emergent coronavirus is SARS-CoV-2, the agent responsible for the current global COVID-19 disease pandemic that has resulted in over 2.8 million infections and 193,710 deaths to date7.
The application of proteomic techniques to the study of these different types of coronaviruses has allowed for a more complete characterization of each virus and its pathogenesis. Proteomic methods were successfully applied to the study of SARS-CoV immediately following the 2003 SARS outbreak and contributed significantly to our understanding of SARS-CoV structure, replication, and pathology, as well as identified potential therapeutic targets. Mass spectrometry-based methods were initially used to characterize the structure and components of SARS infectious virus particles9–11. These studies confirmed virus protein sequences predicted by nucleotide sequencing, identified antigenic virus proteins, located glycosylation sites decorating the virus spike protein necessary for entry into host cells, and revealed host proteins which were incorporated into the virus particles during assembly. An affinity purification mass spectrometry analysis of the coronavirus spike protein led to the identification of angiotensin-converting enzyme 2 (ACE2) as the cell surface receptor for SARS-CoV12. As the same host receptor is also targeted by the novel SARS-CoV-2, these findings led to the recent testing of the clinically approved compound, camostat mesylate, as a mean to block CoV-2 infection13.
Other research teams applied proteomic methods to investigate changes in the cellular proteome during SARS-CoV infection14–16. These studies revealed host processes that are dysregulated during infection for the benefit of virus replication. For instance, the host protein BCL2-associated athanogene 3 (BAG3) was identified as upregulated during SARS-CoV replication16. Knockdown of BAG3 suppressed SARS-CoV replication and protein synthesis, demonstrating its pro-viral function during infection and identifying it as a potential therapeutic target. Another group used mass spectrometry to identify two phosphorylation sites on the virus nucleocapsid (N) protein, which regulates viral RNA transcription and replication17. As phosphorylation impacts the ability of N to bind RNA, this finding could aid in the development of antivirals regulating the phosphorylation status of N. Mass spectrometry was also used in the search for biomarkers of SARS-CoV infection in human plasma samples18–21. These studies provided insight into the pathogenesis of SARS and revealed diagnostic markers, as well as markers correlated with disease progression, prognosis, and viral load. The aim of these studies was to develop a SARS-specific fingerprint that could differentiate SARS patients from non-SARS patients early during infection and predict the expected progression and severity of disease for each individual, allowing for personalized treatment and appropriate resource allocation.
Considering the current SARS-CoV-2 pandemic, proteomic techniques will be highly beneficial for investigating the efficacy of antiviral therapies, identifying new therapeutic targets, and developing fast and effective early diagnostic tests for coronavirus infection. For instance, monitoring virus and host protein levels following treatment with trial antivirals would demonstrate drug efficacy and reveal off-target effects. Proteomics could also be used to identify candidates for the rational design of antivirals targeting pro-viral host processes, which are often more effective long-term treatment options due to the propensity of RNA viruses to mutate. Quantification of temporal changes in host protein levels throughout the time-course of coronavirus infection would illuminate proteins and cellular processes that are dysregulated by coronavirus as potential therapeutic targets. Furthermore, a range of proteomic methods are available for studying host-viral protein-protein and protein-nucleic acid interactions, promising to provide insight into interactions that could be disrupted to restore host defense and inhibit virus replication. Such methods include affinity purification, crosslinking, proximity labeling, and thermal proximity coaggregation. Proteomic techniques could also be used to overcome what has been a major challenge during the current pandemic, i.e., the development of a fast, effective, and reliable diagnostic test for early detection of coronavirus infection. Targeted mass spectrometry could be used to identify diagnostic and prognostic markers of SARS-CoV-2 infection in patient serum samples, similar to investigations done during the 2003 SARS-CoV outbreak18–21. This potential for the implementation of diverse proteomic methods for studying SARS-CoV-2 can already be seen in the impressive number of recent manuscripts either published or in prepublication format on bioRxiv.
The desire of the international scientific community to rapidly respond to the new SARS-CoV-2 pandemic has been evident on all fronts of science, including within the proteomics field. This is exemplified by efforts from the Human Infectious Diseases team (HID-HPP) of the B/D-HPP, as well as the timely organization of the COVID-19 Mass Spectrometry Coalition (covid19-msc.org), spearheaded by Dr. Perdita Barran (University of Manchester). This coalition now involves a continuously growing number of HUPO and HPP scientists, including Drs. Fernando Corrales, Edward Emmott, Andrea Sinz, Catherine Costello, Gilberto B Domont, Stephen Pennington, Yu-Ju Chen, John Yates, and our group to name just a few. Through the combined experience and expertise of scientists globally, we will continue to illuminate the underlying biology and pathogenicity of SARS-CoV-2 and contribute this knowledge toward the development of antiviral treatment options.
1. Greco, T. M., Diner, B. A. & Cristea, I. M. The Impact of Mass Spectrometry–Based Proteomics on Fundamental Discoveries in Virology. Annu. Rev. Virol. (2014) doi:10.1146/annurev-virology-031413-085527.
2. Emmott, E. et al. Quantitative proteomics using SILAC coupled to LC-MS/MS reveals changes in the nucleolar proteome in influenza A virus-infected cells. J. Proteome Res. 9, 5335–5345 (2010).
3. Dove, B. K. et al. A quantitative proteomic analysis of lung epithelial (A549) cells infected with 2009 pandemic influenza A virus using stable isotope labelling with amino acids in cell culture. Proteomics (2012) doi:10.1002/pmic.201100470.
4. Murray, L. A., Sheng, X. & Cristea, I. M. Orchestration of protein acetylation as a toggle for cellular defense and virus replication. Nat. Commun. (2018) doi:10.1038/s41467-018-07179-w.
5. Lum, K. K. et al. Interactome and Proteome Dynamics Uncover Immune Modulatory Associations of the Pathogen Sensing Factor cGAS. Cell Syst. (2018) doi:10.1016/j.cels.2018.10.010.
6. Hashimoto, Y., Sheng, X., Murray-Nerger, L. A. & Cristea, I. M. Temporal dynamics of protein complex formation and dissociation during human cytomegalovirus infection. Nat. Commun. (2020) doi:10.1038/s41467-020-14586-5.
7. Practice, B. B. Coronavirus disease 2019. World Heal. Organ. 2019, 2633 (2020).
8. Ng, L. F. P. & Hiscox, J. A. Coronaviruses in animals and humans. The BMJ (2020) doi:10.1136/bmj.m634.
9. Krokhin, O. et al. Mass spectrometric characterization of proteins from the SARS virus: a preliminary report. Mol. Cell. Proteomics (2003) doi:10.1074/mcp.M300048-MCP200.
10. Ying, W. et al. Proteomic analysis on structural proteins of Severe Acute Respiratory Syndrome coronavirus. in Proteomics (2004). doi:10.1002/pmic.200300676.
11. Neuman, B. W. et al. Proteomics Analysis Unravels the Functional Repertoire of Coronavirus Nonstructural Protein 3. J. Virol. (2008) doi:10.1128/jvi.02631-07.
12. Li, W. et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature (2003) doi:10.1038/nature02145.
13. Hoffmann, M. et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell (2020) doi:10.1016/j.cell.2020.02.052.
14. Zeng, R. et al. Proteomic analysis of SARS associated coronavirus using two-dimensional liquid chromatography mass spectrometry and one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by mass spectroemtric analysis. J. Proteome Res. (2004) doi:10.1021/pr034111j.
15. Jiang, X. S. et al. Quantitative analysis of Severe Acute Respiratory Syndrome (SARS)-associated coronavirus-infected cells using proteomic approaches: Implications for cellular responses to virus infection. Mol. Cell. Proteomics 4, 902–913 (2005) doi: 10.1074/mcp.M400112-MCP200
16. Zhang, L., Zhang, Z. P., Zhang, X. E., Lin, F. S. & Ge, F. Quantitative Proteomics Analysis Reveals BAG3 as a Potential Target To Suppress Severe Acute Respiratory Syndrome Coronavirus Replication. J. Virol. (2010) doi:10.1128/jvi.00213-10.
17. Lin, L. et al. Identification of phosphorylation sites in the nucleocapsid protein (N protein) of SARS-coronavirus. Int. J. Mass Spectrom. (2007) doi:10.1016/j.ijms.2007.05.009.
18. Chen, J. H. et al. Plasma proteome of severe acute respiratory syndrome analyzed by two-dimensional gel electrophoresis and mass spectrometry. Proc. Natl. Acad. Sci. U. S. A. (2004) doi:10.1073/pnas.0407992101.
19. Poon, T. C. W. et al. Serial analysis of plasma proteomic signatures in pediatric patients with severe acute respiratory syndrome and correlation with viral load. Clin. Chem. (2004) doi:10.1373/clinchem.2004.035352.
20. Kang, X. et al. Proteomic fingerprints for potential application to early diagnosis of severe acute respiratory syndrome. Clin. Chem. (2005) doi:10.1373/clinchem.2004.032458.
21. Pang, R. T. K. et al. Serum proteomic fingerprints of adult patients with severe acute respiratory syndrome. Clin. Chem. (2006) doi:10.1373/clinchem.2005.061689.
The Journal of Proteome Research will publish its eighth annual Special Issue dedicated to highlight the progress made on the HUPO Human Proteome Project (HPP). The Special Issue considers research papers encompassing both the Chromosome-Centric Human Proteome Project (C-HPP) and the Biology and Disease Human Proteome Project (B/D-HPP), as well from the Resource Pillars (Antibody, MS, Pathology, and Knowledgebase), and short definitive reports, submitted in the Letters format, on the discovery of a Missing Protein(s). To be considered, the missing protein(s) must meet the Guidelines v 3.0 and be cast in the context of the HPP and biological setting in which they were discovered.
Manuscripts must be submitted by 31st May, 2020 to be considered for this Special Issue. Manuscripts must be submitted electronically through the ACS Paragon Plus Environment online submission system. Specify in the authors’ cover letter that the manuscript is intended for the HPP Special Issue. Editorial triage will determine whether manuscripts are appropriate for the HPP Special Issue, fulfil the HPP Guidelines 3.0 (2019-10-15) checklist and protein evidence based on the 2020-01-17 neXtprot release to be considered for publication. The completed checklist must be included with the cover letter. The full MS data submission to ProteomeXchange must also be completed prior to initial submission, and the PXD number provided in the abstract. As papers are accepted they will go online and be available in time for HUPO-2020. Due to the publication schedule, only papers that are accepted by September 31, 2020 will be published in the December 2020 HPP Special Issue.
Submit your manuscript to Journal of Proteome Research for the 2020 HUPO Human Proteome Project Special Issue. Submission deadline is June 30th, 2020. The Special Issue considers papers encompassing both the Chromosome-Centric Human Proteome Project (C-HPP) and the Biology and Disease Human Proteome Project (B/D-HPP). In addition, we will now consider short definitive reports, submitted in the Letters format, on the discovery of a Missing Protein(s). Click here for more information.
The Annual HUPO Congress in 2019 in Adelaide, Australia is approaching and will again host a rich C-HPP and HPP program and activities to share progress and results of the international chromosome teams and the whole C-HPP. Status reports will be presented on the status of missing protein identification (neXt-MP50) and the identification of functions of uPE1 proteins in the neXt-CP50 projects, to seek new joint projects with B/D-HPP teams, and to discuss the future directions of C-HPP.
HPP Workshop Days
The various activities of the C-HPP are listed and continuously updated on the C-HPP Wiki. Especially relevant are the pre- and post-congress HPP Workshops. On Sunday September 15th is the HPP Investigators Program, Hall A, Adelaide Convention Centre jointly coordinated by Chris Overall and Fernando Corrales. The Post-Congress HPP workshop, organized by Mark Baker, is being held 9 – 5pm, Thursday Sept 19th, Bradley Forum, Level 5 Hawke Building, City West Campus, UniSA, 50 – 55 Nth Terrace, Adelaide, about 500 m west on North Terrace towards the new Hospital. Again, the program is posted on the C-HPP Wiki and the C-HPP Portal.
C-HPP Poster Session
Outside the submitted abstracts stream for HUPO, again we will have a separate C-HPP poster session running the entire meeting. Please bring extra posters relevant to the C-HPP that you wish to present, especially unpublished recent data. Note, abstracts do not have to be uploaded to the HUPO-Adelaide web site, just bring your research along to present. We encourage you to bring additional extra posters for this section to translate your research, highlight your trainees, and accelerate C-HPP discussions. The C-HPP Poster Discussion, led by Gil Omenn will be at morning coffee/tea Tuesday 10:00-10:40 and possibly in the afternoon tea break also. Lightning 2-minute talks at each poster will be followed by Q & A. This will be a key part in deciding Poster Awards!
Please put up the posters Sunday afternoon or Monday morning at the latest to ensure ample viewing and discussion time. We have a great location, posters numbers 1 – 20, just as you enter the main exhibit hall on the left and en route to the Bioinformatics Hub. These posters will be displayed for the entire length of the congress. Protifi (https://www.protifi.com/) is sponsoring 3 @ USD200 C-HPP Poster Awards, which along with Certificates, will be presented at the Awards Ceremony on Wednesday at the close of the congress.
Again, Eric Deutsch has mastered a wide ranging and practical program on bioinformatics challenges (click for the program) in MP hunting, data analysis and implementing the new Human Proteome Project Data Interpretation Guidelines (Version 3.0) in a friendly atmosphere that encourages Q & A and for attendees to come away truly knowing the answer to their questions. The Hub is perfectly located at the main entrance of the exhibit hall to the left, incidentally with the C-HPP posters on one of its outside walls.
The new HPP Data Guidelines v 3.0
A key take home message from the HPP workshop days in Adelaide and the bioinformatics hub will be presentation and discussion on implementation of the new guidelines for MP discovery and promotion to PE1. Please read the preprint here Human Proteome Project Data Interpretation Guidelines (Version 3.0).
C-HPP Annual Report
The C-HPP Annual report can be found here.
The C-HPP Wiki
The C-HPP wiki is updated, but we require your input for the individual chromosome teams. Please refer to Peter Horvatovich for log in info to post and edit entries. Peter will be presenting how to edit the wiki in the bioinformatics hub on Monday, September 16, 2019 at 10:30-11:00 and is available during the meeting to help members work with the wiki. Each chromosome group is also requested to send their respective neXt-MP50 and neXt-CP50 reports and update their chromosome C-HPP Wiki page.
We look forward to seeing you at (C)-HPP events of the HUPO 2019 Congress in Adelaide. Let’s go!
Chris Overall (chair), Young-Ki Paik (co-chair), Lydie Lane (co-chair), Gilberto B. Domont (MAL), Fernando Corrales (MAL), Pengyuan Yang (MAL) and Peter Horvatovich (secretary general).
Vera Ignjatovic,University of Melbourne, Australia
Q: Can you please tell us about when did you first become involved in HUPO activities?Ruedi Aebersold: I got involved with HUPO pretty early. One of the early activities was the formation of what is today the PSI working group. Around 2000 it was pretty clear to us that as proteomics researchers we would run into problems if the computational analysis of MS and MS/MS data could not become more transparent and better benchmarked. We developed in our group at ISB in Seattle some tools that we presented at HUPO meetings, I believe first in Montreal. These included a data representation scheme in xml format (mzXML) developed by Patrick Pedrioli and statistical models developed by Alexey Nesvizhskii and Andy Keller to assign probabilities to peptide identifications (PeptideProphet) and inferred protein identifications (ProteinProphet). Out of these developments and the perceived need to discuss and benchmark these and other tools came the PSI.With Albert Heck and Anne-Claude Gavin I was a co-organizer of the Amsterdam meeting and was subsequently heavily involved in the HPP, specifically the B/D part of the project.
Q: What major achievements over the past 10 years have contributed to the success of HUPO?Ruedi Aebersold: I think the major success of HUPO overall is that it provides a worldwide forum for proteomic scientists and a face of proteomics to the other fields of science. As specific achievements I would name the successful annual congresses, the initiatives which have had a large effect on how proteomic experiments are planned, carried out and reported and the support of young scientists. All these have contributed to increasing the visibility of proteomics.
Q: What made you interested in becoming the HPP-SAB Chair?Ruedi Aebersold:I was for a while chair of the B/D-HPP project before I had to step down due to obligations at my home institution. It is therefore very interesting for me to become involved in the project again in another role. I look forward to catching up on what has happened and to work with the SAB members and the project leaders to further develop the project.
Q: Where do you see the HPP heading both in the short and the long-term?Ruedi Aebersold: I think in the short term and long term the HPP should continue to help making proteomics a mainstream technology for the life sciences including clinical research. The HPP has already accomplished a lot in that direction with providing results, techniques, resources and knowledge towards the exploration of the (human) proteome. Importantly, this has been accomplished in the spirit of international cooperation. I would like to see a convergence of the two HPP directions towards that goal.
Q: What do you think that the SAB can/may deliver in the short and long term?Ruedi Aebersold: I hope that that the SAB can be an effective sounding board, provide feedback on the HPP plans and activities developed by the project leaders and provide suggestions as to how the project could develop. In my opinion, it is important that the roles of the project leadership and the SAB are clearly defined and separate. SAB’s in general should be advisory and not become operationally active or intrusive.
Q: Could you please list three practical steps that all proteomics researchers can take in improving the visibility of proteomics globally?Ruedi Aebersold: Unfortunately, in many circles proteomics still has the reputation of being complicated, slow, expensive and to only work in few places. This is distinctively not the case anymore (if it was ever the case). I think proteomics researchers could and should take steps to counter these wrong impressions. They could do this by: i) conveying the capabilities of the field and the excitement to colleagues in different fields, ii) by collaborating on interesting projects, iii) by focusing the conversations and communication on what is possible as opposed to what is not (yet) possible, i.e. focus communication on solutions and not problems.
Q: What are the major hurdles that proteomics faces on the way to it's integration into daily clinical practice?Ruedi Aebersold: There are of course technical hurdles that need to be overcome. However, I think the main hurdles that hamper integration of proteomics into daily clinical practice (and for that matter into basic life science as well) are access and perception (as explained above).
Q: Last but not least....What advice would you give to Early Career "proteomics practitioners" to best set up themselves for a long and prosperous career?Ruedi Aebersold: The amazing advances in instrumentation and techniques realized over the past few years make the measurement of proteomes routine compared to the situation some years ago and provide data of high quality. To best set themselves up for a successful career in proteomics I would recommend to young scientists to learn as much as possible about experimental design and computational analysis of large datasets, and to learn about the important biological and clinical questions where proteomics can make a unique contribution and then to go for it.
Robert Moritz, Institute for Systems Biology , USA
The Human Proteome Project (HPP) MS-Pillar Phosphopeptide challenge (HPC) resource will present its first findings at the HUPO Congress Adelaide this month. The HPC continues to collect new data and invites new participants to also contribute to this knowledgebase. Participants are again invited to contribute to both phases of phosphopeptide identification methods development by analyzing a set of phosphopeptides by their favorite method and follow up with a method of affinity purification step using the popular ReSyn HUPO affinity kit to see improvements in their methods. Together with our partners, SynPeptide Co. Ltd in Shanghai (www.synpeptide.com) and Resyn Biosciences Pty Ltd in South Africa (www.resynbio.com), the HPP MS-Pillar will provide the SynPeptide-HUPO phosphopeptide mixtures as well as a comprehensive ReSyn phosphopeptide purification kit to use as the affinity method for the HUPO phosphopeptide mixtures. The SynPeptide phospho peptides and the Resyn MagReSyn® kit including the magnet separator are valued at over US$1000 each are provided free to all interested HUPO members. Come by the SynPeptide Booth at the Adelaide Congress to pick up your free set of HUPO phosphopeptide sets and request the ReSyn iMac kits.
Dear HUPO Members,
The Human Proteome Project (HPP) was launched in 2010 under the aegis of HUPO. The HPP was built upon a matrix structure, incorporating existing HUPO scientific initiatives (e.g., plasma, brain, liver proteome, etc), the gene/chromosomal-centric (started 2012 and abbreviated as C-HPP) and protein-biology-disease-centric approaches (also started 2012 and called B/D-HPP). These are now underpinned by 4 resource pillars (affinity/antibody reagents, mass spectrometry, knowledgebase and pathology). The vision of HUPO is that HPP activities will collectively and ultimately lead to breakthroughs in medicine, biotechnology and the life sciences, thereby leaving a legacy of human proteome research.
The HPP continues to make progress, addressing two specific challenges;
In January 2019, Mark Baker (previous HUPO President), took over as Chair of the HPP to carry on the mantle from Gil Omenn (HUPO co-Founder and Chair of the HPP since its inception) in driving the current and future initiatives of the Human Proteome Project. With the expanding goals of the HPP and aggressive timelines to drive the numerous initiatives under the HPP umbrella of activities, we seek to engage a vibrant, well-organized, and goal-oriented proteomics researcher to the newly created 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 2020. Responsibilities of the HPP Co-Chair include:
The HPP is seeking a strong, strategic, vibrant, enthusiastic and collegial leader who would be a suitable candidate to support and represent the HPP. HUPO is keen to ensure regional, gender and early career scientist equity across its management structures. This position is honorary and in line with the many organizational positions within the HUPO executive committee.
Applications will be reviewed and voted on by the HUPO and HPP Executive Committees, and the successful candidate will need to be ratified by HUPO Council at their HUPO2019 Meeting in Adelaide.
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 August 23, 2019.
Marta del Campo Milan, Charlotte Teunissen
We are glad to announce the 29th HUPO Brain Proteome Project (HBPP) Workshop will be held on 27th and 28th of May 2019 in Amsterdam, The Netherlands.
HBPP Spring Workshops cover a wide range of topics relevant to neuroproteomics research. The program is highly dynamic and interactive, and all participants are given the opportunity to give an oral presentation on their research or updates of novel techniques and analytical approaches used in their labs. Workshops have included, for example, sessions on myelin proteomics, autoimmunity, and bioinformatics.
HBPP is committed to a strong clinical and translational focus. Hence, sessions in last meetings were dedicated to proteomics of psychiatric disorders, movement disorders, spinal cord injury & trauma, dementia, and cancers of the CNS. On top of that, there will be a very nice evening program that will allow all the delegates to have relax interactions with a unique local atmosphere.We encourage every researcher interested in brain proteomics, including junior scientists to get in contact and join this event. For more information about the workshop and abstract submission please visit https://www.hbpp2019.com/.
We would like to ask you to extent and share this information between all the researchers and/or in your mailing list. It would be also very helpful if you could include our flyer in your main webpage, which is attached within this email.
Thank you in advance for your collaboration!
Péter Horvatovich, University of Groningen, The Netherlands
The Journal of Proteome Research Special Issue 2018 (Associate Editor: Christopher M. Overall, Guest Editors: Paik, YK, Eric Deutsch, Fernando Corrales, Lydie Lane and Gil Omenn) was published on December 7, 2018 (Volume 17, Issue 12). In this issue, a total of 32 papers covered 4 major research topics: (i) missing proteins (MPs), (ii) uPE1 proteins, (iii) bioinformatics tool development and (iv) biology/disease proteomes. According to the article summarising the progress on identification status and metrics of the Human Proteome Project, the number of missing proteins (PE1+2+3+4) decreased from 2579 to 2186 and the number of proteins with sufficient evidence at proteome level (PE1) reached 17470, which represents 89% of the human proteome, while the number of dubious proteins is 574. From the 17470 PE1 proteins there are mass spectrometry evidence in the Peptide Atlas for 15798 proteins. The launch of the neXt-CP50 pilot project to find at least one function of well identified 1260 PE1 proteins with unknown function (uPE1 proteins) using state-of-the-art gene editing technologies such as CRISPCas or gene silence with miRNA is discussed in Young-Ki Paik et al. Deutsch et al discusses all aspects of the use of spectral libraries and spectral library search in proteomics workflows including quality at library, spectra and peak (fragment ion) levels the used spectral similarity methods, construction of consensus spectra and merging different spectral library following the discussion at the 2017 Dagstuhl Seminar on Computational Proteomics. The work of Macron et al. describe identification of missing proteins in human cerebrospinal fluid following immunodepletion and TMT labeling. This work identified 12 missing proteins candidates from which 8 proteins were identified based on 2 to 6 uniquely mapping peptides and 4 matched a new peptide with a complementary “stranded” single peptide in PeptideAtlas from previous CSF studies. Sun et al. presents a study on human testis, using multiple proteases and high and low pH deep proteomics analysis and identified 14 PE2 MPs after spectrum quality analysis, isobaric post-translational modification, and single amino acid variant filtering, and synthesized peptide matching, from which 3 was testis specific. The study by He et al. used LysargiNase, the trypsin “mirror protease” that cuts before lysine and arginine equally as efficiently as trypsin that cuts after the basic residues, to identify low molecular weight missing proteins and validated 2 MPs from 7MPs candidates. Pullman et al. presented the tool ProteinExplorer, which allows to explore the large amount of reanalysed public proteomics data available in MASSIVE, which allowed to build a spectral library containing 2.1 million precursors matching to 1 million unique peptides and 19000 proteins. The use of ProteinExplorer allowed to validate HPP-compliant evidence for 107 MPs (PE2, PE3, and PE4) and 23 dubious (PE5) proteins.
Michelle Hill, QIMR Berghofer Medical Research Institute, and The University of Queensland, Australia
The 2018 post-HUPO congress HPP workshop kicked off with a new interactive session moderated by Rob Moritz, where selected senior and young investigators each had <5 minutes to share what they found most exciting during the entire HUPO congress. All speakers strove to beat Rob’s musical interlude, most were successful. The floor was then opened to all participants, with great diversity of inputs and interests. This new format was a refreshing and productive start to the workshop.
The HPP Town Hall Meeting session led by Fernando Corrales and Young-Ki Paik outlined the activities and goals for the B/D- and C- HPP, respectively. Mark Baker then presented his vision and strategic plan for the NextGen HPP, with input and discussions from the senior Scientific Advisory Board (SAB) members, Cathy Costello, John Yates and Naoyuki Taniguchi. Although the B/D- and C- HPP branches were organised for logistics in the first phase of HPP, synergistic efforts are being established between various B/D- and C- HPP teams. The SAB further challenged the NextGen HPP leadership team to aim for HPP integration in the coming years.
With the establishment of the Pathology pillar, HPP is inviting external interdisciplinary partners towards clinical translation. Steve Pennington and Henry Rodriguez shared their views and experiences on the strategies for successful international translational research. Finally, Mike Synder delivered insightful grand challenges for the entire field of proteomics.
The post-congress workshop ended on a high note with celebration of Gil Omenn’s leadership of HPP, with refreshments. The well-researched presentation by Mark Baker provided a rare insight to the talents and achievements of Gil.
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