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1.
J Biomed Semantics ; 12(1): 18, 2021 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-34454610

RESUMO

BACKGROUND: With COVID-19 still in its pandemic stage, extensive research has generated increasing amounts of data and knowledge. As many studies are published within a short span of time, we often lose an integrative and comprehensive picture of host-coronavirus interaction (HCI) mechanisms. As of early April 2021, the ImmPort database has stored 7 studies (with 6 having details) that cover topics including molecular immune signatures, epitopes, and sex differences in terms of mortality in COVID-19 patients. The Coronavirus Infectious Disease Ontology (CIDO) represents basic HCI information. We hypothesize that the CIDO can be used as the platform to represent newly recorded information from ImmPort leading the reinforcement of CIDO. METHODS: The CIDO was used as the semantic platform for logically modeling and representing newly identified knowledge reported in the 6 ImmPort studies. A recursive eXtensible Ontology Development (XOD) strategy was established to support the CIDO representation and enhancement. Secondary data analysis was also performed to analyze different aspects of the HCI from these ImmPort studies and other related literature reports. RESULTS: The topics covered by the 6 ImmPort papers were identified to overlap with existing CIDO representation. SARS-CoV-2 viral S protein related HCI knowledge was emphasized for CIDO modeling, including its binding with ACE2, mutations causing different variants, and epitope homology by comparison with other coronavirus S proteins. Different types of cytokine signatures were also identified and added to CIDO. Our secondary analysis of two cohort COVID-19 studies with cytokine panel detection found that a total of 11 cytokines were up-regulated in female patients after infection and 8 cytokines in male patients. These sex-specific gene responses were newly modeled and represented in CIDO. A new DL query was generated to demonstrate the benefits of such integrative ontology representation. Furthermore, IL-10 signaling pathway was found to be statistically significant for both male patients and female patients. CONCLUSION: Using the recursive XOD strategy, six new ImmPort COVID-19 studies were systematically reviewed, the results were modeled and represented in CIDO, leading to the enhancement of CIDO. The enhanced ontology and further seconary analysis supported more comprehensive understanding of the molecular mechanism of host responses to COVID-19 infection.


Assuntos
Ontologias Biológicas , COVID-19 , Interações entre Hospedeiro e Microrganismos , Humanos , Semântica , Glicoproteína da Espícula de Coronavírus/metabolismo
2.
J Biomed Inform ; 120: 103861, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34224898

RESUMO

The current intensive research on potential remedies and vaccinations for COVID-19 would greatly benefit from an ontology of standardized COVID terms. The Coronavirus Infectious Disease Ontology (CIDO) is the largest among several COVID ontologies, and it keeps growing, but it is still a medium sized ontology. Sophisticated CIDO users, who need more than searching for a specific concept, require orientation and comprehension of CIDO. In previous research, we designed a summarization network called "partial-area taxonomy" to support comprehension of ontologies. The partial-area taxonomy for CIDO is of smaller magnitude than CIDO, but is still too large for comprehension. We present here the "weighted aggregate taxonomy" of CIDO, designed to provide compact views at various granularities of our partial-area taxonomy (and the CIDO ontology). Such a compact view provides a "big picture" of the content of an ontology. In previous work, in the visualization patterns used for partial-area taxonomies, the nodes were arranged in levels according to the numbers of relationships of their concepts. Applying this visualization pattern to CIDO's weighted aggregate taxonomy resulted in an overly long and narrow layout that does not support orientation and comprehension since the names of nodes are barely readable. Thus, we introduce in this paper an innovative visualization of the weighted aggregate taxonomy for better orientation and comprehension of CIDO (and other ontologies). A measure for the efficiency of a layout is introduced and is used to demonstrate the advantage of the new layout over the previous one. With this new visualization, the user can "see the forest for the trees" of the ontology. Benefits of this visualization in highlighting insights into CIDO's content are provided. Generality of the new layout is demonstrated.


Assuntos
Ontologias Biológicas , COVID-19 , Doenças Transmissíveis , Compreensão , Humanos , SARS-CoV-2
3.
Database (Oxford) ; 20212021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244718

RESUMO

The Ontology for Biomedical Investigations (OBI) underwent a focused review of assay term annotations, logic and hierarchy with a goal to improve and standardize these terms. As a result, inconsistencies in W3C Web Ontology Language (OWL) expressions were identified and corrected, and additionally, standardized design patterns and a formalized template to maintain them were developed. We describe here this informative and productive process to describe the specific benefits and obstacles for OBI and the universal lessons for similar projects.

4.
Brief Funct Genomics ; 20(4): 235-248, 2021 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-34159360

RESUMO

Omics technologies are widely used in biomedical research. Precision medicine focuses on individual-level disease treatment and prevention. Here, we propose the usage of the term 'precision omics' to represent the combinatorial strategy that applies omics to translate large-scale molecular omics data for precision disease understanding and accurate disease diagnosis, treatment and prevention. Given the complexity of both omics and precision medicine, precision omics requires standardized representation and integration of heterogeneous data types. Ontology has emerged as an important artificial intelligence component to become critical for standard data and metadata representation, standardization and integration. To support precision omics, we propose a precision omics ontology hypothesis, which hypothesizes that the effectiveness of precision omics is positively correlated with the interoperability of ontologies used for data and knowledge integration. Therefore, to make effective precision omics studies, interoperable ontologies are required to standardize and incorporate heterogeneous data and knowledge in a human- and computer-interpretable manner. Methods for efficient development and application of interoperable ontologies are proposed and illustrated. With the interoperable omics data and knowledge, omics tools such as OmicsViz can also be evolved to process, integrate, visualize and analyze various omics data, leading to the identification of new knowledge and hypotheses of molecular mechanisms underlying the outcomes of diseases such as COVID-19. Given extensive COVID-19 omics research, we propose the strategy of precision omics supported by interoperable ontologies, accompanied with ontology-based semantic reasoning and machine learning, leading to systematic disease mechanism understanding and rational design of precision treatment and prevention. SHORT ABSTRACT: Precision medicine focuses on individual-level disease treatment and prevention. Precision omics is a new strategy that applies omics for precision medicine research, which requires standardized representation and integration of individual genetics and phenotypes, experimental conditions, and data analysis settings. Ontology has emerged as an important artificial intelligence component to become critical for standard data and metadata representation, standardization and integration. To support precision omics, interoperable ontologies are required in order to standardize and incorporate heterogeneous data and knowledge in a human- and computer-interpretable manner. With the interoperable omics data and knowledge, omics tools such as OmicsViz can also be evolved to process, integrate, visualize and analyze various omics data, leading to the identification of new knowledge and hypotheses of molecular mechanisms underlying disease outcomes. The precision COVID-19 omics study is provided as the primary use case to illustrate the rationale and implementation of the precision omics strategy.


Assuntos
COVID-19/metabolismo , Genômica , Proteômica , COVID-19/virologia , Humanos , Medicina de Precisão , SARS-CoV-2/isolamento & purificação
5.
Sci Rep ; 11(1): 10763, 2021 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-34031435

RESUMO

Research on drugs against SARS-CoV-2 (cause of COVID-19) has been one of the major world concerns at present. There have been abundant research data and findings in this field. The interference of drugs on gene expression in cell lines, drug-target, protein-virus receptor networks, and immune cell infiltration of the host may provide useful information for anti-SARS-CoV-2 drug research. To simplify the complex bioinformatics analysis and facilitate the evaluation of the latest research data, we developed OmiczViz ( http://medcode.link/omicsviz ), a web tool that has integrated drug-cell line interference data, virus-host protein-protein interactions, and drug-target interactions. To demonstrate the usages of OmiczViz, we analyzed the gene expression data from cell lines treated with chloroquine and ruxolitinib, the drug-target protein networks of 48 anti-coronavirus drugs and drugs bound with ACE2, and the profiles of immune cell infiltration between different COVID-19 patient groups. Our research shows that chloroquine had a regulatory role of the immune response in renal cell line but not in lung cell line. The anti-coronavirus drug-target network analysis suggested that antihistamine of promethaziney and dietary supplement of Zinc might be beneficial when used jointly with antiviral drugs. The immune infiltration analysis indicated that both the COVID-19 patients admitted to the ICU and the elderly with infection showed immune exhaustion status, yet with different molecular mechanisms. The interactive graphic interface of OmiczViz also makes it easier to analyze newly discovered and user-uploaded data, leading to an in-depth understanding of existing findings and an expansion of existing knowledge of SARS-CoV-2. Collectively, OmicsViz is web program that promotes the research on medical agents against SARS-CoV-2 and supports the evaluation of the latest research findings.


Assuntos
Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Interface Usuário-Computador , Enzima de Conversão de Angiotensina 2/química , Enzima de Conversão de Angiotensina 2/metabolismo , Antivirais/química , Antivirais/metabolismo , Antivirais/farmacologia , COVID-19/metabolismo , COVID-19/patologia , COVID-19/virologia , Linhagem Celular , Cloroquina/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Internet , Ligação Proteica , Pirazóis/farmacologia , Índice de Gravidade de Doença
7.
Nucleic Acids Res ; 49(W1): W671-W678, 2021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-34009334

RESUMO

Vaccination is one of the most significant inventions in medicine. Reverse vaccinology (RV) is a state-of-the-art technique to predict vaccine candidates from pathogen's genome(s). To promote vaccine development, we updated Vaxign2, the first web-based vaccine design program using reverse vaccinology with machine learning. Vaxign2 is a comprehensive web server for rational vaccine design, consisting of predictive and computational workflow components. The predictive part includes the original Vaxign filtering-based method and a new machine learning-based method, Vaxign-ML. The benchmarking results using a validation dataset showed that Vaxign-ML had superior prediction performance compared to other RV tools. Besides the prediction component, Vaxign2 implemented various post-prediction analyses to significantly enhance users' capability to refine the prediction results based on different vaccine design rationales and considerably reduce user time to analyze the Vaxign/Vaxign-ML prediction results. Users provide proteome sequences as input data, select candidates based on Vaxign outputs and Vaxign-ML scores, and perform post-prediction analysis. Vaxign2 also includes precomputed results from approximately 1 million proteins in 398 proteomes of 36 pathogens. As a demonstration, Vaxign2 was used to effectively analyse SARS-CoV-2, the coronavirus causing COVID-19. The comprehensive framework of Vaxign2 can support better and more rational vaccine design. Vaxign2 is publicly accessible at http://www.violinet.org/vaxign2.


Assuntos
Desenho de Fármacos , Internet , Aprendizado de Máquina , Software , Vacinas , Vacinologia/métodos , Antígenos Virais/química , Antígenos Virais/imunologia , COVID-19/virologia , Vacinas contra COVID-19/química , Vacinas contra COVID-19/imunologia , Epitopos/química , Epitopos/imunologia , Humanos , Proteoma , SARS-CoV-2/química , SARS-CoV-2/imunologia , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas/química , Vacinas/imunologia , Fluxo de Trabalho
8.
Environ Microbiol ; 23(9): 5222-5238, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33893759

RESUMO

Clostridioides difficile is a Gram-positive, spore-forming, toxin-producing anaerobe that can cause nosocomial antibiotic-associated intestinal disease. Although the production of toxin A (TcdA) and toxin B (TcdB) contribute to the main pathogenesis of C. difficile, the mechanism of TcdA and TcdB release from cell remains unclear. In this study, we identified and characterized a new cell wall hydrolase Cwl0971 (CDR20291_0971) from C. difficile R20291, which is involved in bacterial autolysis. The gene 0971 deletion mutant (R20291Δ0971) generated with CRISPR-AsCpfI exhibited significantly delayed cell autolysis and increased cell viability compared to R20291, and the purified Cwl0971 exhibited hydrolase activity for Bacillus subtilis cell wall. Meanwhile, 0971 gene deletion impaired TcdA and TcdB release due to the decreased cell autolysis in the stationary/late phase of cell growth. Moreover, sporulation of the mutant strain decreased significantly compared to the wild type strain. In vivo, the defect of Cwl0971 decreased fitness over the parent strain in a mouse infection model. Collectively, Cwl0971 is involved in cell wall lysis and cell viability, which affects toxin release, sporulation, germination, and pathogenicity of R20291, indicating that Cwl0971 could be an attractive target for C. difficile infection therapeutics and prophylactics.

9.
Virulence ; 12(1): 1258-1270, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33904371

RESUMO

Severe Helicobacter pylori-linked gastric disorders are especially prevalent in the East Asia region. The ability of H. pylori to cause different clinical outcomes is thought to be associated with unique sets of its genetic features. However, only few genetic features have been definitively linked to specific gastrointestinal pathologies. Genome heterogeneity of clinical H. pylori strains from patients with four different gastric disorders was studied to explore the population structure and molecular genomic features and their association with pathogenicity. Population analysis showed that 92.9% of the Shanghai H. pylori isolates were clustered in the East Asia group. Among 2,866 genes detected in all genomes, 1,146 genes formed the core genome, whereas 209 unique genes were detected in individual disease groups. The unique genes of peptic ulcer and gastric cancer groups represented the inorganic ion transport and metabolism function gene clusters. Sixteen virulence genes were detected with statistically different detection rates among the four disease groups. Furthermore, 127 clustered regularly interspaced short palindromic repeats were found with significantly different rates in the four disease groups. A total of 337 putative genomic islands were identified, and three genomic islands were individually found in more than 10% of strains. The genomic islands included several metabolism-associated genes and many genes with unknown function. In total, 88 sequence types were detected among the 112 Shanghai H. pylori isolates. Our study provides an essential milestone in the mapping of specific genomic features and their functions to identify factors needed to induce specific gastric disorders in H. pylori.

10.
Front Immunol ; 12: 639491, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33777032

RESUMO

Vaccines stimulate various immune factors critical to protective immune responses. However, a comprehensive picture of vaccine-induced immune factors and pathways have not been systematically collected and analyzed. To address this issue, we developed VaximmutorDB, a web-based database system of vaccine immune factors (abbreviated as "vaximmutors") manually curated from peer-reviewed articles. VaximmutorDB currently stores 1,740 vaccine immune factors from 13 host species (e.g., human, mouse, and pig). These vaximmutors were induced by 154 vaccines for 46 pathogens. Top 10 vaximmutors include three antibodies (IgG, IgG2a and IgG1), Th1 immune factors (IFN-γ and IL-2), Th2 immune factors (IL-4 and IL-6), TNF-α, CASP-1, and TLR8. Many enriched host processes (e.g., stimulatory C-type lectin receptor signaling pathway, SRP-dependent cotranslational protein targeting to membrane) and cellular components (e.g., extracellular exosome, nucleoplasm) by all the vaximmutors were identified. Using influenza as a model, live attenuated and killed inactivated influenza vaccines stimulate many shared pathways such as signaling of many interleukins (including IL-1, IL-4, IL-6, IL-13, IL-20, and IL-27), interferon signaling, MARK1 activation, and neutrophil degranulation. However, they also present their unique response patterns. While live attenuated influenza vaccine FluMist induced significant signal transduction responses, killed inactivated influenza vaccine Fluarix induced significant metabolism of protein responses. Two different Yellow Fever vaccine (YF-Vax) studies resulted in overlapping gene lists; however, they shared more portions of pathways than gene lists. Interestingly, live attenuated YF-Vax simulates significant metabolism of protein responses, which was similar to the pattern induced by killed inactivated Fluarix. A user-friendly web interface was generated to access, browse and search the VaximmutorDB database information. As the first web-based database of vaccine immune factors, VaximmutorDB provides systematical collection, standardization, storage, and analysis of experimentally verified vaccine immune factors, supporting better understanding of protective vaccine immunity.


Assuntos
Anticorpos Antivirais/imunologia , Imunidade/imunologia , Fatores Imunológicos/imunologia , Vacinas/imunologia , Animais , Bases de Dados Factuais , Humanos , Internet , Transdução de Sinais/imunologia , Vacinação/métodos
11.
Kidney Int ; 99(3): 498-510, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33637194

RESUMO

Chronic kidney disease (CKD) and acute kidney injury (AKI) are common, heterogeneous, and morbid diseases. Mechanistic characterization of CKD and AKI in patients may facilitate a precision-medicine approach to prevention, diagnosis, and treatment. The Kidney Precision Medicine Project aims to ethically and safely obtain kidney biopsies from participants with CKD or AKI, create a reference kidney atlas, and characterize disease subgroups to stratify patients based on molecular features of disease, clinical characteristics, and associated outcomes. An additional aim is to identify critical cells, pathways, and targets for novel therapies and preventive strategies. This project is a multicenter prospective cohort study of adults with CKD or AKI who undergo a protocol kidney biopsy for research purposes. This investigation focuses on kidney diseases that are most prevalent and therefore substantially burden the public health, including CKD attributed to diabetes or hypertension and AKI attributed to ischemic and toxic injuries. Reference kidney tissues (for example, living-donor kidney biopsies) will also be evaluated. Traditional and digital pathology will be combined with transcriptomic, proteomic, and metabolomic analysis of the kidney tissue as well as deep clinical phenotyping for supervised and unsupervised subgroup analysis and systems biology analysis. Participants will be followed prospectively for 10 years to ascertain clinical outcomes. Cell types, locations, and functions will be characterized in health and disease in an open, searchable, online kidney tissue atlas. All data from the Kidney Precision Medicine Project will be made readily available for broad use by scientists, clinicians, and patients.


Assuntos
Injúria Renal Aguda , Insuficiência Renal Crônica , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/terapia , Adulto , Humanos , Rim , Medicina de Precisão , Estudos Prospectivos , Proteômica , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/terapia
12.
Sci Data ; 8(1): 16, 2021 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-33441564

RESUMO

Our systematic literature collection and annotation identified 106 chemical drugs and 31 antibodies effective against the infection of at least one human coronavirus (including SARS-CoV, SAR-CoV-2, and MERS-CoV) in vitro or in vivo in an experimental or clinical setting. A total of 163 drug protein targets were identified, and 125 biological processes involving the drug targets were significantly enriched based on a Gene Ontology (GO) enrichment analysis. The Coronavirus Infectious Disease Ontology (CIDO) was used as an ontological platform to represent the anti-coronaviral drugs, chemical compounds, drug targets, biological processes, viruses, and the relations among these entities. In addition to new term generation, CIDO also adopted various terms from existing ontologies and developed new relations and axioms to semantically represent our annotated knowledge. The CIDO knowledgebase was systematically analyzed for scientific insights. To support rational drug design, a "Host-coronavirus interaction (HCI) checkpoint cocktail" strategy was proposed to interrupt the important checkpoints in the dynamic HCI network, and ontologies would greatly support the design process with interoperable knowledge representation and reasoning.


Assuntos
Antivirais/farmacologia , Infecções por Coronavirus/tratamento farmacológico , Conjuntos de Dados como Assunto , Desenho de Fármacos , Humanos , Bases de Conhecimento , Coronavírus da Síndrome Respiratória do Oriente Médio , Vírus da SARS , SARS-CoV-2
13.
Nucleic Acids Res ; 49(D1): D1207-D1217, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33264411

RESUMO

The Human Phenotype Ontology (HPO, https://hpo.jax.org) was launched in 2008 to provide a comprehensive logical standard to describe and computationally analyze phenotypic abnormalities found in human disease. The HPO is now a worldwide standard for phenotype exchange. The HPO has grown steadily since its inception due to considerable contributions from clinical experts and researchers from a diverse range of disciplines. Here, we present recent major extensions of the HPO for neurology, nephrology, immunology, pulmonology, newborn screening, and other areas. For example, the seizure subontology now reflects the International League Against Epilepsy (ILAE) guidelines and these enhancements have already shown clinical validity. We present new efforts to harmonize computational definitions of phenotypic abnormalities across the HPO and multiple phenotype ontologies used for animal models of disease. These efforts will benefit software such as Exomiser by improving the accuracy and scope of cross-species phenotype matching. The computational modeling strategy used by the HPO to define disease entities and phenotypic features and distinguish between them is explained in detail.We also report on recent efforts to translate the HPO into indigenous languages. Finally, we summarize recent advances in the use of HPO in electronic health record systems.


Assuntos
Ontologias Biológicas , Biologia Computacional/métodos , Bases de Dados Factuais , Doença/genética , Genoma , Fenótipo , Software , Animais , Modelos Animais de Doenças , Genótipo , Humanos , Recém-Nascido , Cooperação Internacional , Internet , Triagem Neonatal/métodos , Farmacogenética/métodos , Terminologia como Assunto
14.
Curr Pharm Des ; 27(7): 900-910, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33238868

RESUMO

Vaccination is one of the most important innovations in human history. It has also become a hot research area in a new application - the development of new vaccines against non-infectious diseases such as cancers. However, effective and safe vaccines still do not exist for many diseases, and where vaccines exist, their protective immune mechanisms are often unclear. Although licensed vaccines are generally safe, various adverse events, and sometimes severe adverse events, still exist for a small population. Precision medicine tailors medical intervention to the personal characteristics of individual patients or sub-populations of individuals with similar immunity-related characteristics. Precision vaccinology is a new strategy that applies precision medicine to the development, administration, and post-administration analysis of vaccines. Several conditions contribute to make this the right time to embark on the development of precision vaccinology. First, the increased level of research in vaccinology has generated voluminous "big data" repositories of vaccinology data. Secondly, new technologies such as multi-omics and immunoinformatics bring new methods for investigating vaccines and immunology. Finally, the advent of AI and machine learning software now makes possible the marriage of Big Data to the development of new vaccines in ways not possible before. However, something is missing in this marriage, and that is a common language that facilitates the correlation, analysis, and reporting nomenclature for the field of vaccinology. Solving this bioinformatics problem is the domain of applied biomedical ontology. Ontology in the informatics field is human- and machine-interpretable representation of entities and the relations among entities in a specific domain. The Vaccine Ontology (VO) and Ontology of Vaccine Adverse Events (OVAE) have been developed to support the standard representation of vaccines, vaccine components, vaccinations, host responses, and vaccine adverse events. Many other biomedical ontologies have also been developed and can be applied in vaccine research. Here, we review the current status of precision vaccinology and how ontological development will enhance this field, and propose an ontology-based precision vaccinology strategy to support precision vaccine research and development.


Assuntos
Vacinas , Vacinologia , Biologia Computacional , Humanos , Software , Vacinação
15.
Physiol Genomics ; 53(1): 1-11, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33197228

RESUMO

Comprehensive and spatially mapped molecular atlases of organs at a cellular level are a critical resource to gain insights into pathogenic mechanisms and personalized therapies for diseases. The Kidney Precision Medicine Project (KPMP) is an endeavor to generate three-dimensional (3-D) molecular atlases of healthy and diseased kidney biopsies by using multiple state-of-the-art omics and imaging technologies across several institutions. Obtaining rigorous and reproducible results from disparate methods and at different sites to interrogate biomolecules at a single-cell level or in 3-D space is a significant challenge that can be a futile exercise if not well controlled. We describe a "follow the tissue" pipeline for generating a reliable and authentic single-cell/region 3-D molecular atlas of human adult kidney. Our approach emphasizes quality assurance, quality control, validation, and harmonization across different omics and imaging technologies from sample procurement, processing, storage, shipping to data generation, analysis, and sharing. We established benchmarks for quality control, rigor, reproducibility, and feasibility across multiple technologies through a pilot experiment using common source tissue that was processed and analyzed at different institutions and different technologies. A peer review system was established to critically review quality control measures and the reproducibility of data generated by each technology before their being approved to interrogate clinical biopsy specimens. The process established economizes the use of valuable biopsy tissue for multiomics and imaging analysis with stringent quality control to ensure rigor and reproducibility of results and serves as a model for precision medicine projects across laboratories, institutions and consortia.

16.
Nat Rev Nephrol ; 16(11): 686-696, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32939051

RESUMO

An important need exists to better understand and stratify kidney disease according to its underlying pathophysiology in order to develop more precise and effective therapeutic agents. National collaborative efforts such as the Kidney Precision Medicine Project are working towards this goal through the collection and integration of large, disparate clinical, biological and imaging data from patients with kidney disease. Ontologies are powerful tools that facilitate these efforts by enabling researchers to organize and make sense of different data elements and the relationships between them. Ontologies are critical to support the types of big data analysis necessary for kidney precision medicine, where heterogeneous clinical, imaging and biopsy data from diverse sources must be combined to define a patient's phenotype. The development of two new ontologies - the Kidney Tissue Atlas Ontology and the Ontology of Precision Medicine and Investigation - will support the creation of the Kidney Tissue Atlas, which aims to provide a comprehensive molecular, cellular and anatomical map of the kidney. These ontologies will improve the annotation of kidney-relevant data, and eventually lead to new definitions of kidney disease in support of precision medicine.


Assuntos
Atlas como Assunto , Ontologias Biológicas , Nefropatias/classificação , Medicina de Precisão , Big Data , Humanos , Fenótipo
17.
bioRxiv ; 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32817949

RESUMO

The current COVID-19 pandemic caused by SARS-CoV-2 has resulted in millions of confirmed cases and thousands of deaths globally. Extensive efforts and progress have been made to develop effective and safe vaccines against COVID-19. A primary target of these vaccines is the SARS-CoV-2 spike (S) protein, and many studies utilized structural vaccinology techniques to either stabilize the protein or fix the receptor-binding domain at certain states. In this study, we extended an evolutionary protein design algorithm, EvoDesign, to create thousands of stable S protein variants without perturbing the surface conformation and B cell epitopes of the S protein. We then evaluated the mutated S protein candidates based on predicted MHC-II T cell promiscuous epitopes as well as the epitopes' similarity to human peptides. The presented strategy aims to improve the S protein's immunogenicity and antigenicity by inducing stronger CD4 T cell response while maintaining the protein's native structure and function. The top EvoDesign S protein candidate (Design-10705) recovered 31 out of 32 MHC-II T cell promiscuous epitopes in the native S protein, in which two epitopes were present in all seven human coronaviruses. This newly designed S protein also introduced nine new MHC-II T cell promiscuous epitopes and showed high structural similarity to its native conformation. The proposed structural vaccinology method provides an avenue to rationally design the antigen's structure with increased immunogenicity, which could be applied to the rational design of new COVID-19 vaccine candidates.

18.
J Am Med Inform Assoc ; 27(7): 1046-1056, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32626903

RESUMO

OBJECTIVE: The goal of this study is to develop a robust Time Event Ontology (TEO), which can formally represent and reason both structured and unstructured temporal information. MATERIALS AND METHODS: Using our previous Clinical Narrative Temporal Relation Ontology 1.0 and 2.0 as a starting point, we redesigned concept primitives (clinical events and temporal expressions) and enriched temporal relations. Specifically, 2 sets of temporal relations (Allen's interval algebra and a novel suite of basic time relations) were used to specify qualitative temporal order relations, and a Temporal Relation Statement was designed to formalize quantitative temporal relations. Moreover, a variety of data properties were defined to represent diversified temporal expressions in clinical narratives. RESULTS: TEO has a rich set of classes and properties (object, data, and annotation). When evaluated with real electronic health record data from the Mayo Clinic, it could faithfully represent more than 95% of the temporal expressions. Its reasoning ability was further demonstrated on a sample drug adverse event report annotated with respect to TEO. The results showed that our Java-based TEO reasoner could answer a set of frequently asked time-related queries, demonstrating that TEO has a strong capability of reasoning complex temporal relations. CONCLUSION: TEO can support flexible temporal relation representation and reasoning. Our next step will be to apply TEO to the natural language processing field to facilitate automated temporal information annotation, extraction, and timeline reasoning to better support time-based clinical decision-making.


Assuntos
Ontologias Biológicas , Registros Eletrônicos de Saúde , Tempo , Sistemas de Apoio a Decisões Clínicas , Humanos , Processamento de Linguagem Natural , Web Semântica
19.
Front Immunol ; 11: 1581, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32719684

RESUMO

To ultimately combat the emerging COVID-19 pandemic, it is desired to develop an effective and safe vaccine against this highly contagious disease caused by the SARS-CoV-2 coronavirus. Our literature and clinical trial survey showed that the whole virus, as well as the spike (S) protein, nucleocapsid (N) protein, and membrane (M) protein, have been tested for vaccine development against SARS and MERS. However, these vaccine candidates might lack the induction of complete protection and have safety concerns. We then applied the Vaxign and the newly developed machine learning-based Vaxign-ML reverse vaccinology tools to predict COVID-19 vaccine candidates. Our Vaxign analysis found that the SARS-CoV-2 N protein sequence is conserved with SARS-CoV and MERS-CoV but not from the other four human coronaviruses causing mild symptoms. By investigating the entire proteome of SARS-CoV-2, six proteins, including the S protein and five non-structural proteins (nsp3, 3CL-pro, and nsp8-10), were predicted to be adhesins, which are crucial to the viral adhering and host invasion. The S, nsp3, and nsp8 proteins were also predicted by Vaxign-ML to induce high protective antigenicity. Besides the commonly used S protein, the nsp3 protein has not been tested in any coronavirus vaccine studies and was selected for further investigation. The nsp3 was found to be more conserved among SARS-CoV-2, SARS-CoV, and MERS-CoV than among 15 coronaviruses infecting human and other animals. The protein was also predicted to contain promiscuous MHC-I and MHC-II T-cell epitopes, and the predicted linear B-cell epitopes were found to be localized on the surface of the protein. Our predicted vaccine targets have the potential for effective and safe COVID-19 vaccine development. We also propose that an "Sp/Nsp cocktail vaccine" containing a structural protein(s) (Sp) and a non-structural protein(s) (Nsp) would stimulate effective complementary immune responses.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Aprendizado de Máquina , Pandemias , Pneumonia Viral , Vacinas Virais , Animais , Betacoronavirus/genética , Betacoronavirus/imunologia , COVID-19 , Vacinas contra COVID-19 , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/genética , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Epitopos de Linfócito B/genética , Epitopos de Linfócito B/imunologia , Humanos , Imunogenicidade da Vacina , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Pandemias/prevenção & controle , Pneumonia Viral/epidemiologia , Pneumonia Viral/genética , Pneumonia Viral/imunologia , Pneumonia Viral/prevenção & controle , SARS-CoV-2 , Proteínas Virais/genética , Proteínas Virais/imunologia , Vacinas Virais/genética , Vacinas Virais/imunologia
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