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Checkout the latest HUPOST released today: February HUPOST 2021
Stephen Pennington, HUPO Past President, UCD Conway Institute, Ireland
It has been a genuine privilege and honour to have had the opportunity to serve as HUPO President for the past two years. The COVID-19 global pandemic has made the last 9-10 months very challenging for the HUPO community and leadership team (Executive Committee). Our thoughts go to those in our community who have been directly impacted and especially those who have lost loved ones.
I’m sure we are all conscious of the devastating negative health and social consequences of COVID-19. Amongst the very many negatives it is reassuring, and perhaps necessary, to hold onto some positive outcomes from the pandemic. The increase in public and professional awareness of the science of biology and virology, of diagnostic testing and vaccine development has been remarkable to witness. Proteomics has been at the front and centre of these efforts. Likewise, the importance of global collaboration and sharing of data has been in the spotlight. This is something that isn’t new to HUPO as global collaboration and data sharing has been at the heart of HUPO and its various initiatives for many years. We should all be proud of the contribution proteomics has made and continues to make to all aspects of COVID-19 research and clinical practice. It behoves us all to publicise these efforts and capitalise the increased public awareness and support for biological sciences to more generally promote the importance of the very real global impact of proteomics research. Raising the profile of proteomics and its “success stories” has been a consistent priority for the HPP and we should now be poised to progress this with renewed vigour.
HUPO is a global organisation that promotes equality and diversity. The dramatic events of 2020 highlighted the importance of making all aware of this. I am very grateful to Sue Weintraub not only for her steadfast support as Vice-President but also for carefully crafting HUPO’s diversity statement.
The HUPO Congresses are a highlight of the HUPO year and they have continued to showcase the very best of proteomics, presented by the very best of proteomics researchers at all stages of their scientific experience. In 2019, we had the opportunity to participate in a wonderful congress in Adelaide, Australia. Organising such a successful Congress takes a huge amount of effort so without naming names I’d like to thank the local organisers for hosting the superb science, the HPP day and allied events such as the ICPC and Immuno-peptidomics meetings and combining all this with a superbly enjoyable experience.
At the start of 2020 we were all excited by the prospect of another annual Congress – this time in Stockholm, Sweden. In a very timely manner and as the COVID pandemic was gripping the world the Stockholm local organising committee advised against a ‘face-to-face’ Congress. The decision was made to postpone the Stockholm meeting (to 2021) and hold a virtual Congress in 2020 – a first for HUPO. A virtual Organising Committee (vOC) was assembled and worked tirelessly with colleagues from ICS (our core professional conference organiser) to plan and deliver HUPO Connect 2020. In addition, to the regular repertoire of proteomics research, the Congress provided an opportunity to highlight the key role proteomics has played in COVID-19 research. At a personal level, the chance to participate in the vOC; witnessing the development of our early stage career researchers, and the Congress supporting the development of a library of the recorded presentations were highlights of 2020. There have been many other proteomics highlights including, but not limited to, the publication of the High-Stringency Blueprint of the Human Proteome, the publication of the annual HPP metrics paper and the celebration of 20 years of the Human Protein Atlas.
Of course, challenges (opportunities) remain for the continued development of proteomics and I’m very confident that HUPO under leadership of YuJu Chen will continue to catalyse the pace of proteomics successes. YuJu will be ably supported by the HUPO EC and, under the leadership of Rob Mortiz, the HPP EC.
Finally, I’d like to encourage all members and especially existing and newly elected HUPO Council members to get involved in HUPO’s activities. The old adage – the more you put in the more you get out – is as true now as it ever was.
Thank you all for giving me a wonderful opportunity and particularly to those who have guided and supported me in the last two years. It’s perhaps not wise to single out any individuals but here goes anyway….! I’d particularly like to thank Jenny van Eyk and Michelle Hill for their consistent and much valued wise counsel and support and Chelsea Prangnell for her support and willingness to share the benefit of her ‘HUPO experience’.
Yu-Ju Chen, HUPO President, Institute of Chemistry, Academia Sinica, Taiwan
It is truly a great honor and a big responsibility to serve as the HUPO president in the coming two years. Since the past January, I have joined the HUPO EC and witnessed the great efforts from the leadership team led by Past President Steve Pennington and Vice-President Susan Weintraub. Among the many impressive HUPO achievements, perhaps most notable and quite unique to everyone is the HUPO Connect 2020 – the very first virtual congress for HUPO. The HUPO leadership together with supports from HPP, committees, council members, speakers and sponsors have jointly turned the challenges of COVID-19 outbreak into a landmark congress in the history of HUPO. Big thank you to Steve and Sue for your contribution and congratulation to the achievements made in the past two years. From my personal view, this is the uniqueness of HUPO that we have devoted and passionate colleagues to create an inclusive and energetic infrastructure for promoting proteomics activities. I am looking forward to working with you all to enjoy proteomics activities and to translate it into knowledge in biology, health and disease as well as tools to impact our life.
Despite the unexpected and devastating economic and social disruption caused by the COVID-19 outbreak, it indeed created an opportunity to demonstrate the global proteomic exploration to enhance our molecular understanding for the emerging disease and to facilitate development of new diagnostic and therapeutic strategies. Exciting researches are exemplified in the power of multidimensional data integrating proteomics with clinical data and machine-learning-based models for risk stratification of patients, construction of SARS-CoV-2 protein interaction network to reveal the pathogenesis mechanism as well as to identify targets for drug repurposing, identification of biomarkers and rapid development of high throughput diagnosis tools for the clinical trajectory of patients. In addition to continue to promote the International collaboration in infectious diseases from the HUPO initiative, I look forward to facilitate efforts in standardization of protocols and diagnosis methods and multi-nation clinical trial within the HUPO community. The example of COVID19 may also apply to other diseases to promote precision medicine for sustainable health.
The Human Proteome Project (HPP) is well recognized as the signature for HUPO’s research activities. The release of “ A High-Stringency Blueprint of the Human Proteome” in 2020 established the legacy of the first decade of the HUPO HPP in defining the constitutions of the complex proteome with 90% coverage based on stringent criteria. I would like to express my great appreciation to the HPP leadership led by Gil Omenn, Mark Baker and Robert Moritz, advisory board and many colleagues who have contributed to HPP in the past years. Looking ahead, the human proteome blueprint is definitely the foundation of future proteomics research.
Despite our many successes, there remains much to be done to demonstrate the utility of proteomics. To date, advancements of genomics have changed the face of biology and medicine. Despite the fact that proteins are the molecules to be targeted for many therapies, however, gene testing is gold standard and protein-based diagnosis is not well accepted as clinical assay yet. Stepping into the next 10 years of HPP, I believe that proteomics will take a similar path like genomics to create benefits of our life. To speed up the process, we can jointly define focused themes, reachable milestones and strategies to transform proteomics into utilizes in many aspects of life, such as clinical care, prevention medicine, precision agriculture, and food safety.
“If you want to go fast, go alone. If you want to go far, go together”- African proverb.
This is my firm belief that joint wisdoms and collaborative efforts always inspire new ideas with success beyond the expectation of a single mind. After 20 years since the launch of HUPO in 2001, we are now stepping into the next phase of proteomics. It is time to redefine the forward-looking goals and strategic planning for HUPO to create impact to biology, health and society. I will continue the inclusive culture of HUPO and sincerely encourage our members and everyone who loves proteomics from different part of the world to work together and demonstrate the power of proteomics to impact our life in the future.
Catchup on the latest HUPO updates in the December HUPOST: https://conta.cc/3oip1Wz.
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.
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.
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.
The Human Proteome Project (HPP) releases the first Human Proteome Organization (HUPO)-endorsed, high-stringency Human Proteome Blueprint in Nature Communications (see https://www.nature.com/articles/s41467-020-19045-9). Like the draft “shotgun” Human Genome Project of the Human Genome Organization (HUGO), the HPP has now reached a significant decadal milestone of >90% completion of the Human Proteome that is referred to as the human proteome “parts-list”. This effort recognizes significant community efforts that enabled data inspection and re-analysis, culminating in a high stringency (i.e., rigorous, exacting standards for post-acquisition data processing and protein inferences made from MS spectral data) HPP knowledge base (KB). Additionally, to illustrate the many parallel historical innovations made by the scientific community that have driven proteomics advances, HUPO has created a publicly available interactive historical timeline to be released coincident with publication of this article (hupo.org/Proteomics-Timeline).
The HPP’s mission is to reanalyze and integrate community proteomics data with high-stringency processes, bringing increased granularity to our molecular understanding of the dynamic nature of the proteome, including all its modifications, and their relation to human biology and disease. This mission aligns closely with HUPO’s motto “translating the code of life”, providing crucial information that genomics per se cannot deliver. Completion of the HPP will enhance our understanding of human molecular and cellular biology, laying better foundations for diagnostic, prognostic, therapeutic and precision medicine applications.
In 2010, the Human Proteome Organization launched the Human Proteome Project (HPP), as an international endeavor to create a framework for global collaboration, data sharing and quality assurance, enhancing accurate annotation of the genome-encoded proteome. Over the last decade, the key resources of the HPP (the Human Protein Atlas, PeptideAtlas, MassIVE and neXtProt knowledge bases) have driven the development and refinement of guidelines and metrics to understand the definitive identification of any protein of the human proteome. Their high-stringency reanalysis of community data led to the current status of >90% identification completion rate of the Human Proteome. This knowledge is essential to discern the proteome’s role in health and disease. Here, on behalf of the proteomics community, we report the inaugural high-stringency human proteome project blueprint, illustrating roles in the diagnosis and treatment of cancers, cardiovascular and infectious disease pathologies.
By Erika Hunting, Stanford University, USA
Researchers demonstrate how understanding protein levels can provide insights into regulation, secretome, metabolism, and human disease.
Unraveling the genetic basis of many human diseases is a daunting task. However, understanding where the products of disease-related genes act can provide clues into disease formation. Presently, scientists examine the RNA -- the first product of a gene -- to infer the tissue where genes act. Unfortunately, there is a downfall to this method: the level of protein -- the active end product of a gene -- often correlates poorly with RNA levels. Thus, generating a map of proteins may be a more revealing approach to understanding the cardinal foundation of disease development.
In a paper published on Sept. 11 in Cell, researchers in the lab of Michael Snyder, Stanford B. Ascherman Professor and Chair of Genetics and Director of Genomics and Personalized Medicine at Stanford University School of Medicine, generated the most comprehensive protein map to date. The map shows where proteins are expressed throughout the human body,providing new insights into regulation, secretome, metabolism, and human diseases. The researchers measured relative protein levels from over 12,000 genes across 32 normal human tissues. Tissue-specific proteins were identified and compared to RNA data. Information from tissue-specific proteins could lead to novel explanations of disease phenotype that could not have been deduced by RNA information alone.
"The tissue-specific distribution of proteins can provide an in-depth view of complex biological processes that require the interplay of multiple organs,” said lead author Lihua Jiang, a proteomics expert in the Snyder Laboratory responsible for proteomics profiling of host samples of the project. “Analysis of enzymes involved in amino acid metabolism revealed different roles of each organ as well as novel organs (heart, stomach, pancreas) that are important for metabolic control. We envision this kind of analysis can shed light on the understanding of many biological processes.”
Correlation between RNA and Protein Levels
Previous studies of protein levels have already been performed. However, most of these studies focused on in-depth protein identification and analysis, and the protein measurements were either less accurate or less precise. Moreover, most samples in these studies did not have the corresponding RNA information from the same tissue, making the comparison of RNA and protein levels difficult. Although recent studies have greatly advanced tissue-protein identification, a broader study with accurate measurements for both protein and RNA levels within the same tissues is needed to understand protein level differences from RNA. Additionally, no previous studies have used tissue-specific protein data to systematically examine human biological processes and diseases.
This Snyder Lab study offered a good opportunity to characterize the correlation between protein and RNA, as data were generated from the same tissue specimens. For many genes, the Stanford team found that only the RNA (not their corresponding proteins) were present at a significant level, while for other genes, it was the opposite -- the protein was detected and not the RNA. These results indicate that tissue-specific functions cannot be distinguished on the basis of RNA levels alone.
Insights into Disease and Drug Targets
“Lastly, for genetic diseases caused by mutations in protein-coding regions, the protein information across tissues can suggest the affected organs and explain specific disease symptoms that cannot be explained by genomic studies. As such, the protein data generated in this study is expected to provide valuable insights into human biology and disease," said Dr. Michael Snyder.
Importantly, for many genes, enrichment only occurs at the protein level and not at the RNA level, so protein expression information may provide insights into the underlying disease mechanisms that cannot be identified using RNA information alone. This demonstrates the importance of collecting protein expression information for the understanding of disease phenotype. Thus, the researchers systematically investigated the protein expression patterns of genetic diseases and found many cases where disease-associated proteins are present in tissues that manifest disease-related pathophysiology; many of these would not be evident from RNA analysis.
For example, Bardet-Biedl syndrome (BBS) is a genetic disorder caused by mutations in at least 14 different genes and affects many parts of the body. BBS-affiliated vision loss, polydactyly, obesity, and other abnormalities can be explained by specific gene mutations but many are still largely unknown; tissue-specific protein expression information might explain some of the clinical symptoms. The researchers detected proteins from 11/14 BBS genes, among which seven are enriched in the pituitary and five are in the brain, muscle, heart, or liver. Abnormality of proteins in the pituitary can broadly affect developmental processes and perhaps cause obesity, diabetes, or hypogonadism observed in BBS patients. The abnormalities in proteins in the brain, muscle, heart, and liver might also contribute to defects such as intellectual disability, delayed motor skills, and conditions that involve the heart, liver, and digestive systems.
Leigh syndrome is another genetic disease that is associated with mutations in as many as 75 genes. Most of the affected proteins are involved in energy production in the mitochondria. Of the 67/75 proteins observed, 52 showed-up in metabolically active tissues, such as the heart, muscle, brain, and stomach. Some of these proteins were present in all affected tissues and some were only in one or several tissues; their different distributions might cause different tissue-related clinical symptoms. For example, the characteristic progressive loss of mental and movement abilities of Leigh syndrome is most likely related to protein abnormalities in the brain and muscle. Some individuals develop hypertrophic cardiomyopathy which could be caused by mutations in proteins present in the heart. The first signs of Leigh syndrome are vomiting, diarrhea, and difficulty swallowing -- which could be explained by the abnormality of proteins found in the stomach.
Finally, the team identified 1,329 potential drug-targeted proteins, about half of which are FDA approved drug targets. These drug-targeted proteins span 742 different tissues, and 368 are present in more than one tissue. For drug-targeted proteins present outside of the target organ, the drug may have unintended side effects in the off-target tissue. For example, valproic acid is an anticonvulsant drug that works through the inhibition of a protein in the brain. Snyder’s team showed that this drug-targeted protein is also enriched in the liver and pancreas, suggesting the underlying cause of reported liver and pancreas toxicity side effects.
“This study provides a valuable resource for us to understand human biology and diseases from proteins which are closer to phenotype. We envision some tissue specific proteins can be used as better biomarkers for diagnosis as well.” said Dr. Michael Snyder.
Find A Quantitative Proteome Map of the Human Body article here....
Prof. Michael Snyder's Lab
Prof. Michael Snyder and Lihua Jiang
The Human Protein Atlas (HPA) team plans to release a series of "Movie of the month" during 2020 and 2021. The scientific movies allow for taking a journey into the body through 3D videos that transport you deep inside various organs. The imaging is based on antibody-based profiling of tissues and light sheet microscopy.
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