The availability of human genome sequence has transformed biomedical research over the past decade. However, an equivalent map for the human proteome with direct measurements of proteins and peptides does not exist yet. Here, we present a draft map of the human proteome using high resolution Fourier transform mass spectrometry. In-depth proteomic profiling of 30 histologically normal human samples including 17 adult tissues, 7 fetal tissues and 6 purified primary hematopoietic cells resulted in identification of proteins encoded by 17,294 genes accounting for ~84% of the total annotated protein-coding genes in humans. A unique and comprehensive strategy for proteogenomic analysis enabled us to discover a number of novel protein-coding regions, which includes translated pseudogenes, non-coding RNAs and upstream ORFs. This large human proteome catalog (available as an interactive web-based resource at http://www.humanproteomemap.org) will complement available human genome and transcriptome data to accelerate biomedical research in health and disease.

What started as a cluster of patients with a mysterious respiratory illness in Wuhan, China, in December 2019, was later determined to be coronavirus disease 2019 (COVID-19). The pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel Betacoronavirus , was subsequently isolated as the causative agent. SARS-CoV-2 is transmitted by respiratory droplets and fomites and presents clinically with fever, fatigue, myalgias, conjunctivitis, anosmia, dysgeusia, sore throat, nasal congestion, cough, dyspnea, nausea, vomiting, and/or diarrhea. In most critical cases, symptoms can escalate into acute respiratory distress syndrome accompanied by a runaway inflammatory cytokine response and multiorgan failure. As of this article's publication date, COVID-19 has spread to approximately 200 countries and territories, with over 4.3 million infections and more than 290,000 deaths as it has escalated into a global pandemic. Public health concerns mount as the situation evolves with an increasing number of infection hotspots around the globe. New information about the virus is emerging just as rapidly. This has led to the prompt development of clinical patient risk stratification tools to aid in determining the need for testing, isolation, monitoring, ventilator support, and disposition. COVID-19 spread is rapid, including imported cases in travelers, cases among close contacts of known infected individuals, and community-acquired cases without a readily identifiable source of infection. Critical shortages of personal protective equipment and ventilators are compounding the stress on overburdened healthcare systems. The continued challenges of social distancing, containment, isolation, and surge capacity in already stressed hospitals, clinics, and emergency departments have led to a swell in technologically-assisted care delivery strategies, such as telemedicine and web-based triage. As the race to develop an effective vaccine intensifies, several clinical trials of antivirals and immune modulators are underway, though no reliable COVID-19-specific therapeutics (inclusive of some potentially effective single and multi-drug regimens) have been identified as of yet. With many nations and regions declaring a state of emergency, unprecedented quarantine, social distancing, and border closing efforts are underway. Implementation of social and physical isolation measures has caused sudden and profound economic hardship, with marked decreases in global trade and local small business activity alike, and full ramifications likely yet to be felt. Current state-of-science, mitigation strategies, possible therapies, ethical considerations for healthcare workers and policymakers, as well as lessons learned for this evolving global threat and the eventual return to a “new normal” are discussed in this article.

The study of the human urinary proteome has the potential to offer significant insights into normal physiology as well as disease pathology. The information obtained from such studies could be applied to the diagnosis of various diseases. The high sensitivity, resolution, and mass accuracy of the latest generation of mass spectrometers provides an opportunity to accurately catalog the proteins present in human urine, including those present at low levels. To this end, we carried out a comprehensive analysis of human urinary proteome from healthy individuals using high-resolution Fourier transform mass spectrometry. Importantly, we used the Orbitrap for detecting ions in both MS (resolution 60 000) and MS/MS (resolution 15 000) modes. To increase the depth of our analysis, we characterized both unfractionated as well as lectin-enriched proteins in our experiments. In all, we identified 1823 proteins with less than 1% false discovery rate, of which 671 proteins have not previously been reported as constituents of human urine. This data set should serve as a comprehensive reference list for future studies aimed at identification and characterization of urinary biomarkers for various diseases.

BackgroundOsteoarthritis is a chronic musculoskeletal disorder characterized mainly by progressive degradation of the hyaline cartilage. Patients with osteoarthritis often postpone seeking medical help, which results in the diagnosis being made at an advanced stage of cartilage destruction. Sustained efforts are needed to identify specific markers that might help in early diagnosis, monitoring disease progression and in improving therapeutic outcomes. We employed a multipronged proteomic approach, which included multiple fractionation strategies followed by high resolution mass spectrometry analysis to explore the proteome of synovial fluid obtained from osteoarthritis patients. In addition to the total proteome, we also enriched glycoproteins from synovial fluid using lectin affinity chromatography.ResultsWe identified 677 proteins from synovial fluid of patients with osteoarthritis of which 545 proteins have not been previously reported. These novel proteins included ADAM-like decysin 1 (ADAMDEC1), alanyl (membrane) aminopeptidase (ANPEP), CD84, fibulin 1 (FBLN1), matrix remodelling associated 5 (MXRA5), secreted phosphoprotein 2 (SPP2) and spondin 2 (SPON2). We identified 300 proteins using lectin affinity chromatography, including the glycoproteins afamin (AFM), attractin (ATRN), fibrillin 1 (FBN1), transferrin (TF), tissue inhibitor of metalloproteinase 1 (TIMP1) and vasorin (VSN). Gene ontology analysis confirmed that a majority of the identified proteins were extracellular and are mostly involved in cell communication and signaling. We also confirmed the expression of ANPEP, dickkopf WNT signaling pathway inhibitor 3 (DKK3) and osteoglycin (OGN) by multiple reaction monitoring (MRM) analysis of osteoarthritis synovial fluid samples.ConclusionsWe present an in-depth analysis of the synovial fluid proteome from patients with osteoarthritis. We believe that the catalog of proteins generated in this study will further enhance our knowledge regarding the pathophysiology of osteoarthritis and should assist in identifying better biomarkers for early diagnosis.