Open Targets Platform: supporting systematic drug-target identification and prioritisation.
- Authors
- Ochoa, David; Hercules, Andrew; Carmona, Miguel; Suveges, Daniel; Gonzalez-Uriarte, Asier; Malangone, Cinzia; Miranda, Alfredo; Fumis, Luca; Carvalho-Silva, Denise; Spitzer, Michaela; Baker, Jarrod; Ferrer, Javier; Raies, Arwa; Razuvayevskaya, Olesya; Faulconbridge, Adam; Petsalaki, Eirini; Mutowo, Prudence; Machlitt-Northen, Sandra; Peat, Gareth; McAuley, Elaine; Ong, Chuang Kee; Mountjoy, Edward; Ghoussaini, Maya; Pierleoni, Andrea; Papa, Eliseo; Pignatelli, Miguel; Koscielny, Gautier; Karim, Mohd; Schwartzentruber, Jeremy; Hulcoop, David G; Dunham, Ian; McDonagh, Ellen M
- Year
- 2021
- Journal
- Nucleic acids research
- PMID
- 33196847
- DOI
- 10.1093/nar/gkaa1027
- PMCID
- PMC7779013
The Open Targets Platform (https://www.targetvalidation.org/) provides users with a queryable knowledgebase and user interface to aid systematic target identification and prioritisation for drug discovery based upon underlying evidence. It is publicly available and the underlying code is open source. Since our last update two years ago, we have had 10 releases to maintain and continuously improve evidence for target-disease relationships from 20 different data sources. In addition, we have integrated new evidence from key datasets, including prioritised targets identified from genome-wide CRISPR knockout screens in 300 cancer models (Project Score), and GWAS/UK BioBank statistical genetic analysis evidence from the Open Targets Genetics Portal. We have evolved our evidence scoring framework to improve target identification. To aid the prioritisation of targets and inform on the potential impact of modulating a given target, we have added evaluation of post-marketing adverse drug reactions and new curated information on target tractability and safety. We have also developed the user interface and backend technologies to improve performance and usability. In this article, we describe the latest enhancements to the Platform, to address the fundamental challenge that developing effective and safe drugs is difficult and expensive.
Overview of the Open Targets Platform. (A) The Platform data model includes the entities targets, diseases and drugs. The relationships between the three entities is shown. (B) Annotation of biomedical entities is provided from 26 underlying data sources. (C) The target identification and prioritisation framework is based on evidence from 20 evidence sources providing targetβdisease relationships. EFO expansion allows for capture of further associations between targets and diseases/phenotypes. For each targetβdisease association, the underlying data sources that provide evidence are scored, and an overall scoring ranks targets associated with the disease. Targets are further prioritised based on additional key attributes including tractability, safety and expression. (D) Platform data is accessible via a user interface or programmatically via the EMBL-EBI FTP server, API endpoints or as downloads via Google Cloud. Abbreviations: D, disease/phenotype; Dr, drug; EFO, Experimental factor ontology; T, target.
Post-marketing pharmacovigilance analysis for Pazopanib. Significant adverse events associated with Pazopanib (CHEMBL477772), based on systematic analysis of all available FDA Adverse Event Reporting System. Analysis is displayed in the Open Targets Platform for all drugs with available data.
Target - disease evidence in the Open Targets Platform. Data sources are grouped by data typeβleft. Unique validated evidence available in each of the platform releases since April 2016 (16.04)βmiddle. Relevant changes in the most recent period are annotated in further detailβright. A full list of the data sources with references is found in Supplementary Table S2.
Enhanced user interface and new functionality. Platform interface redesign for PTGS2 target profile page. (A) Identifiers and links to other resources are provided at the top of the page. Target information widgets outline the available data (in blue). By clicking on a widget, the user is taken to that section. Sections can be rearranged by the user, allowing them to personalise their experience. (B) The βKnown drugsβ widget takes the user to a sortable and filterable table including information on clinical candidates or approved drugs, sourced from ChEMBL (12). (C) The βTractabilityβ section provides a druggability assessment by small molecule, antibody or other modality.
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| An integrated approach to identifying sex-specific genes, transcription factors, and pathways relevant to Alzheimer's disease. | LΓ³pez-CerdΓ‘n A et al. | β | 2024 | β |
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| Autoencoder-based phenotyping of ophthalmic images highlights genetic loci influencing retinal morphology and provides informative biomarkers. | Sergouniotis PI et al. | β | 2024 | β |
| CardiOmics signatures reveal therapeutically actionable targets and drugs for cardiovascular diseases. | Ramos-Medina MJ et al. | β | 2024 | β |
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| Comparison of B-Cell Lupus and Lymphoma Using a Novel Immune Imbalance Transcriptomics Algorithm Reveals Potential Therapeutic Targets. | Rapier-Sharman N et al. | β | 2024 | β |
| Contextual AI models for single-cell protein biology. | Li MM et al. | β | 2024 | β |
| CoPheScan: phenome-wide association studies accounting for linkage disequilibrium. | Manipur I et al. | β | 2024 | β |
| Deciphering the molecular landscape of rheumatoid arthritis offers new insights into the stratified treatment for the condition. | Chang MJ et al. | β | 2024 | β |
| Deep learning-based design and experimental validation of a medicine-like human antibody library. | Rajagopal N et al. | β | 2024 | β |
| Development of a human genetics-guided priority score for 19,365 genes and 399 drug indications. | Duffy Γ et al. | β | 2024 | β |
| Diagnostic utility of exome sequencing followed by research reanalysis in human brain malformations. | Kooshavar D et al. | β | 2024 | β |
| DiPPI: A Curated Data Set for Drug-like Molecules in Protein-Protein Interfaces. | Cankara F et al. | β | 2024 | β |
| Drugging the entire human proteome: Are we there yet? | Smith MD et al. | β | 2024 | β |
| Drug Repurposing Approach to Identify Candidate Drug Molecules for Hepatocellular Carcinoma. | Baser T et al. | β | 2024 | β |
| Gastric cancer actionable genomic alterations across diverse populations worldwide and pharmacogenomics strategies based on precision oncology. | EcheverrΓa-GarcΓ©s G et al. | β | 2024 | β |
| Genetic and Epigenetic Landscape for Drug Development in Polycystic Ovary Syndrome. | Chen Y et al. | β | 2024 | β |
| Genetic and multi-omic risk assessment of Alzheimer's disease implicates core associated biological domains. | Cary GA et al. | β | 2024 | β |
| Genome-wide association neural networks identify genes linked to family history of Alzheimer's disease. | Ghose U et al. | β | 2024 | β |
| Genome-Wide Association Study of Treatment-Resistant Depression: Shared Biology With Metabolic Traits. | Kang J et al. | β | 2024 | β |
| Human Genetics and Genomics for Drug Target Identification and Prioritization: Open Targets' Perspective. | McDonagh EM et al. | β | 2024 | β |
| Identification of Circulating Plasma Proteins as a Mediator of Hypertension-Driven Cardiac Remodeling: A Mediation Mendelian Randomization Study. | Hu Y et al. | β | 2024 | β |
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| Integrative functional genomic analyses identify genetic variants influencing skin pigmentation in Africans. | Feng Y et al. | β | 2024 | β |
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| Mining patents with large language models elucidates the chemical function landscape. | Kosonocky CW et al. | β | 2024 | β |
| Pan-cancer analysis of PLAU indicates its potential prognostic value and correlation with neutrophil infiltration in BLCA. | Shi K et al. | β | 2024 | β |
| Partial correlation network analysis identifies coordinated gene expression within a regional cluster of COPD genome-wide association signals. | Gentili M et al. | β | 2024 | β |
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| Plasma Glutaminyl-Peptide Cyclotransferase Mediates Glucosamine-Metabolism-Driven Protection Against Hypertension: A Mendelian Randomization Study. | Ge F et al. | β | 2024 | β |
| Potential candidates from a functional food <i>Zanthoxyli Pericarpium</i> (Sichuan pepper) for the management of hyperuricemia: high-through virtual screening, network pharmacology and dynamics simulations. | Chen M et al. | β | 2024 | β |
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| ProtVar: mapping and contextualizing human missense variation. | Stephenson JD et al. | β | 2024 | β |
| Raynaud phenomenon: from GWAS to drug repurposing. | Herrick AL et al. | β | 2024 | β |
| Secondary Analysis of Human Bulk RNA-Seq Dataset Suggests Potential Mechanisms for Letrozole Resistance in Estrogen-Positive (ER+) Breast Cancer. | Sutherland L et al. | β | 2024 | β |
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| Significance of chitinase-3-like protein 1 in the pathogenesis of inflammatory diseases and cancer. | Yu JE et al. | β | 2024 | β |
| The effects of methylphenidate and atomoxetine on Drosophila brain at single-cell resolution and potential drug repurposing for ADHD treatment. | Qu S et al. | β | 2024 | β |
| The impact of exercise on gene regulation in association with complex trait genetics. | Vetr NG et al. | β | 2024 | β |
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| The pharmacoepigenetic paradigm in cancer treatment. | OcaΓ±a-Paredes B et al. | β | 2024 | β |
| The text2term tool to map free-text descriptions of biomedical terms to ontologies. | GonΓ§alves RS et al. | β | 2024 | β |
| THOC6 is a novel biomarker of glioma and a target of anti-glioma drugs: An analysis based on bioinformatics and molecular docking. | Wei C et al. | β | 2024 | β |
| Triangulating evidence in health sciences with Annotated Semantic Queries. | Liu Y et al. | β | 2024 | β |
| Unraveling druggable cancer-driving proteins and targeted drugs using artificial intelligence and multi-omics analyses. | LΓ³pez-CortΓ©s A et al. | β | 2024 | β |
| Unveiling new genetic insights in rheumatoid arthritis for drug discovery through Taxonomy3 analysis. | Kozlowska J et al. | β | 2024 | β |
| Worldwide analysis of actionable genomic alterations in lung cancer and targeted pharmacogenomic strategies. | EcheverrΓa-GarcΓ©s G et al. | β | 2024 | β |
| A community Biased Signaling Atlas. | Caroli J et al. | β | 2023 | β |
| A deep transcriptome meta-analysis reveals sex differences in multiple sclerosis. | CatalΓ -Senent JF et al. | β | 2023 | β |
| ADRA2A and IRX1 are putative risk genes for Raynaud's phenomenon. | Hartmann S et al. | β | 2023 | β |
| A Drug Repurposing Pipeline Based on Bladder Cancer Integrated Proteotranscriptomics Signatures. | Mokou M et al. | β | 2023 | β |
| An in vitro approach to understand contribution of kidney cells to human urinary extracellular vesicles. | Barreiro K et al. | β | 2023 | β |
| A publication-wide association study (PWAS), historical language models to prioritise novel therapeutic drug targets. | Narganes-CarlΓ³n D et al. | β | 2023 | β |
| A review of genetic risk in systemic lupus erythematosus. | Guga S et al. | β | 2023 | β |
| Artificial intelligence for neurodegenerative experimental models. | Marzi SJ et al. | β | 2023 | β |
| Brain transcriptome-wide association study implicates novel risk genes underlying schizophrenia risk. | Zhang C et al. | β | 2023 | β |
| Comprehensive epigenomic profiling reveals the extent of disease-specific chromatin states and informs target discovery in ankylosing spondylitis. | Brown AC et al. | β | 2023 | β |
| Cross-disorder genetic analysis of immune diseases reveals distinct gene associations that converge on common pathways. | Demela P et al. | β | 2023 | β |
| Developing a cluster-based approach for deciphering complexity in individuals with neurodevelopmental differences. | Cuppens T et al. | β | 2023 | β |
| Effectively utilizing publicly available databases for cancer target evaluation. | Croft D et al. | β | 2023 | β |
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| Evidence of shared genetic factors in the etiology of gastrointestinal disorders and endometriosis and clinical implications for disease management. | Yang F et al. | β | 2023 | β |
| Exploiting the Stemness and Chemoresistance Transcriptome of Ewing Sarcoma to Identify Candidate Therapeutic Targets and Drug-Repurposing Candidates. | Roundhill EA et al. | β | 2023 | β |
| Fathers' preconception smoking and offspring DNA methylation. | Kitaba NT et al. | β | 2023 | β |
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| FinnGen provides genetic insights from a well-phenotyped isolated population. | Kurki MI et al. | β | 2023 | β |
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| Genome-wide association analyses define pathogenic signaling pathways and prioritize drug targets for IgA nephropathy. | Kiryluk K et al. | β | 2023 | β |
| Genome-wide association analysis and Mendelian randomization proteomics identify drug targets for heart failure. | Rasooly D et al. | β | 2023 | β |
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| High throughput sequencing revealed enhanced cell cycle signaling in SLE patients. | Yang M et al. | β | 2023 | β |
| Identification of asthma-related genes using asthmatic blood eQTLs of Korean patients. | Kim DJ et al. | β | 2023 | β |
| Identification of Potential Therapeutic Targets on the Level of DNA/mRNAs, Proteins and Metabolites: A Systematic Mapping Review of Scientific Texts' Fragments from Open Targets. | Pogodin PV et al. | β | 2023 | β |
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| Integrated multi-omics approach to distinct molecular characterization and classification of early-onset colorectal cancer. | Du M et al. | β | 2023 | β |
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| Liver-Specific Polygenic Risk Score Is Associated with Alzheimer's Disease Diagnosis. | Panyard DJ et al. | β | 2023 | β |
| Modern drug discovery for inflammatory bowel disease: The role of computational methods. | Johnson TO et al. | β | 2023 | β |
| Molecular characterization of Richter syndrome identifies de novo diffuse large B-cell lymphomas with poor prognosis. | BrosΓ©us J et al. | β | 2023 | β |
| Mpox Knowledge Graph: a comprehensive representation embedding chemical entities and associated biology of Mpox. | Karki R et al. | β | 2023 | β |
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| Multiomic prediction of therapeutic targets for human diseases associated with protein phase separation. | Lim CM et al. | β | 2023 | β |
| Multiplatform-Integrated Identification of Melatonin Targets for a Triad of Psychosocial-Sleep/Circadian-Cardiometabolic Disorders. | Campos LA et al. | β | 2023 | β |
| OncoRTT: Predicting novel oncology-related therapeutic targets using BERT embeddings and omics features. | Thafar MA et al. | β | 2023 | β |
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| Pan-cancer analysis revealing that PTPN2 is an indicator of risk stratification for acute myeloid leukemia. | Wang X et al. | β | 2023 | β |
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| Sex-Specific Silica Nanoparticle Protein Corona Compositions Exposed to Male and Female BALB/c Mice Plasmas. | Ashkarran AA et al. | β | 2023 | β |
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| Single-cell-led drug repurposing for Alzheimer's disease. | Parolo S et al. | β | 2023 | β |
| Somatic mutations alter the differentiation outcomes of iPSC-derived neurons. | Puigdevall P et al. | β | 2023 | β |
| Synthetic lethality prediction in DNA damage repair, chromatin remodeling and the cell cycle using multi-omics data from cell lines and patients. | Markowska M et al. | β | 2023 | β |
| Systematic comparison of Mendelian randomisation studies and randomised controlled trials using electronic databases. | Sobczyk MK et al. | β | 2023 | β |
| Targeting synthetic lethal paralogs in cancer. | Ryan CJ et al. | β | 2023 | β |
| The benefits and pitfalls of machine learning for biomarker discovery. | Ng S et al. | β | 2023 | β |
| The impact of AlphaFold Protein Structure Database on the fields of life sciences. | Varadi M et al. | β | 2023 | β |
| The International Mouse Phenotyping Consortium: comprehensive knockout phenotyping underpinning the study of human disease. | Groza T et al. | β | 2023 | β |
| The next-generation Open Targets Platform: reimagined, redesigned, rebuilt. | Ochoa D et al. | β | 2023 | β |
| Transcriptome- and proteome-wide association studies nominate determinants of kidney function and damage. | Schlosser P et al. | β | 2023 | β |
| Transforming drug discovery with a high-throughput AI-powered platform: A 5-year experience with Patrimony. | Blaudin de ThΓ© FX et al. | β | 2023 | β |
| Uncovering the complex relationship between balding, testosterone and skin cancers in men. | Ong JS et al. | β | 2023 | β |
| Using a Network-Based Analysis Approach to Investigate the Involvement of <i>S. aureus</i> in the Pathogenesis of Granulomatosis with Polyangiitis. | Rowland G et al. | β | 2023 | β |
| Using chemical and biological data to predict drug toxicity. | Liu A et al. | β | 2023 | β |
| 3D-Beacons: decreasing the gap between protein sequences and structures through a federated network of protein structure data resources. | Varadi M et al. | β | 2022 | β |
| Advancing drug safety science by integrating molecular knowledge with post-marketing adverse event reports. | Soldatos TG et al. | β | 2022 | β |
| A Knowledge Graph-Enhanced Tensor Factorisation Model for Discovering Drug Targets. | Ye C et al. | β | 2022 | β |
| AlphaFold illuminates half of the dark human proteins. | Binder JL et al. | β | 2022 | β |
| Applications of Artificial Intelligence in Drug Design: Opportunities and Challenges. | Thomas M et al. | β | 2022 | β |
| A practical guideline of genomics-driven drug discovery in the era of global biobank meta-analysis. | Namba S et al. | β | 2022 | β |
| ARN25068, a versatile starting point towards triple GSK-3Ξ²/FYN/DYRK1A inhibitors to tackle tau-related neurological disorders. | Demuro S et al. | β | 2022 | β |
| Artificial intelligence-enhanced drug design and development: Toward a computational precision medicine. | Moingeon P et al. | β | 2022 | β |
| A single-cell based precision medicine approach using glioblastoma patient-specific models. | Park JH et al. | β | 2022 | β |
| Causal reasoning over knowledge graphs leveraging drug-perturbed and disease-specific transcriptomic signatures for drug discovery. | Domingo-FernΓ‘ndez D et al. | β | 2022 | β |
| Complex Portal 2022: new curation frontiers. | Meldal BHM et al. | β | 2022 | β |
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| Comprehensive and integrative analyses identify TYW5 as a schizophrenia risk gene. | Zhang C et al. | β | 2022 | β |
| Computationally prioritized drugs inhibit SARS-CoV-2 infection and syncytia formation. | Serra A et al. | β | 2022 | β |
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| Diseases 2.0: a weekly updated database of disease-gene associations from text mining and data integration. | Grissa D et al. | β | 2022 | β |
| Disentangling Signatures of Selection Before and After European Colonization in Latin Americans. | Mendoza-Revilla J et al. | β | 2022 | β |
| DrugnomeAI is an ensemble machine-learning framework for predicting druggability of candidate drug targets. | Raies A et al. | β | 2022 | β |
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| ELF5 is a potential respiratory epithelial cell-specific risk gene for severe COVID-19. | Pietzner M et al. | β | 2022 | β |
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| Genomic Evidence Supports the Recognition of Endometriosis as an Inflammatory Systemic Disease and Reveals Disease-Specific Therapeutic Potentials of Targeting Neutrophil Degranulation. | Bao C et al. | β | 2022 | β |
| GOing Forward With the Cardiac Conduction System Using Gene Ontology. | Chloe Li KY et al. | β | 2022 | β |
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| Investigation of the mechanism of Shen Qi Wan prescription in the treatment of T2DM via network pharmacology and molecular docking. | Zhao P et al. | β | 2022 | β |
| Joint Secondary Transcriptomic Analysis of Non-Hodgkin's B-Cell Lymphomas Predicts Reliance on Pathways Associated with the Extracellular Matrix and Robust Diagnostic Biomarkers. | Rapier-Sharman N et al. | β | 2022 | β |
| Knowledge graph analytics platform with LINCS and IDG for Parkinson's disease target illumination. | Yang JJ et al. | β | 2022 | β |
| Knowledge Graphs for Indication Expansion: An Explainable Target-Disease Prediction Method. | Gurbuz O et al. | β | 2022 | β |
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| Mendelian randomization of circulating proteome identifies actionable targets in heart failure. | Moncla LM et al. | β | 2022 | β |
| Meta-Analysis of Two Human RNA-seq Datasets to Determine Periodontitis Diagnostic Biomarkers and Drug Target Candidates. | Moreno C et al. | β | 2022 | β |
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| Network Pharmacology and Molecular Docking Study on the Multi-Target Mechanisms of <i>Aloe vera</i> for Non-Alcoholic Steatohepatitis Treatment. | Nguyen TK et al. | β | 2022 | β |
| New Drug Design Avenues Targeting Alzheimer's Disease by Pharmacoinformatics-Aided Tools. | ArruΓ© L et al. | β | 2022 | β |
| PiER: web-based facilities tailored for genetic target prioritisation harnessing human disease genetics, functional genomics and protein interactions. | Fang H | β | 2022 | β |
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| Proteomics of Aqueous Humor as a Source of Disease Biomarkers in Retinoblastoma. | Galardi A et al. | β | 2022 | β |
| Reply to Zhu etΒ al.: Implications of <i>CHRNB1</i> and <i>ERBB2</i> in the pathobiology of myasthenia gravis. | Chia R et al. | β | 2022 | β |
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| StarGazer: A Hybrid Intelligence Platform for Drug Target Prioritization and Digital Drug Repositioning Using Streamlit. | Lee C et al. | β | 2022 | β |
| Stroke genetics informs drug discovery and risk prediction across ancestries. | Mishra A et al. | β | 2022 | β |
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| Text Mining Protocol to Retrieve Significant Drug-Gene Interactions from PubMed Abstracts. | Anand S et al. | β | 2022 | β |
| The genetic backbone of ankylosing spondylitis: how knowledge of genetic susceptibility informs our understanding and management of disease. | Kenyon M et al. | β | 2022 | β |
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| Identification of Potential Genetic Biomarkers and Target Genes of Peri-Implantitis Using Bioinformatics Tools. | Zhang X et al. | β | 2021 | β |
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| The 2021 Nucleic Acids Research database issue and the online molecular biology database collection. | Rigden DJ et al. | β | 2021 | β |
| The COVID-19 Data Portal: accelerating SARS-CoV-2 and COVID-19 research through rapid open access data sharing. | Harrison PW et al. | β | 2021 | β |
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