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1.
Nucleic Acids Res ; 51(D1): D690-D699, 2023 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-36263822

RESUMO

The Comprehensive Antibiotic Resistance Database (CARD; card.mcmaster.ca) combines the Antibiotic Resistance Ontology (ARO) with curated AMR gene (ARG) sequences and resistance-conferring mutations to provide an informatics framework for annotation and interpretation of resistomes. As of version 3.2.4, CARD encompasses 6627 ontology terms, 5010 reference sequences, 1933 mutations, 3004 publications, and 5057 AMR detection models that can be used by the accompanying Resistance Gene Identifier (RGI) software to annotate genomic or metagenomic sequences. Focused curation enhancements since 2020 include expanded ß-lactamase curation, incorporation of likelihood-based AMR mutations for Mycobacterium tuberculosis, addition of disinfectants and antiseptics plus their associated ARGs, and systematic curation of resistance-modifying agents. This expanded curation includes 180 new AMR gene families, 15 new drug classes, 1 new resistance mechanism, and two new ontological relationships: evolutionary_variant_of and is_small_molecule_inhibitor. In silico prediction of resistomes and prevalence statistics of ARGs has been expanded to 377 pathogens, 21,079 chromosomes, 2,662 genomic islands, 41,828 plasmids and 155,606 whole-genome shotgun assemblies, resulting in collation of 322,710 unique ARG allele sequences. New features include the CARD:Live collection of community submitted isolate resistome data and the introduction of standardized 15 character CARD Short Names for ARGs to support machine learning efforts.


Assuntos
Curadoria de Dados , Bases de Dados Factuais , Resistência Microbiana a Medicamentos , Aprendizado de Máquina , Antibacterianos/farmacologia , Genes Bacterianos , Funções Verossimilhança , Software , Anotação de Sequência Molecular
2.
Nucleic Acids Res ; 48(D1): D517-D525, 2020 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-31665441

RESUMO

The Comprehensive Antibiotic Resistance Database (CARD; https://card.mcmaster.ca) is a curated resource providing reference DNA and protein sequences, detection models and bioinformatics tools on the molecular basis of bacterial antimicrobial resistance (AMR). CARD focuses on providing high-quality reference data and molecular sequences within a controlled vocabulary, the Antibiotic Resistance Ontology (ARO), designed by the CARD biocuration team to integrate with software development efforts for resistome analysis and prediction, such as CARD's Resistance Gene Identifier (RGI) software. Since 2017, CARD has expanded through extensive curation of reference sequences, revision of the ontological structure, curation of over 500 new AMR detection models, development of a new classification paradigm and expansion of analytical tools. Most notably, a new Resistomes & Variants module provides analysis and statistical summary of in silico predicted resistance variants from 82 pathogens and over 100 000 genomes. By adding these resistance variants to CARD, we are able to summarize predicted resistance using the information included in CARD, identify trends in AMR mobility and determine previously undescribed and novel resistance variants. Here, we describe updates and recent expansions to CARD and its biocuration process, including new resources for community biocuration of AMR molecular reference data.


Assuntos
Bases de Dados Genéticas , Farmacorresistência Bacteriana , Genes Bacterianos , Software , Bactérias/efeitos dos fármacos , Bactérias/genética , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo
3.
Aust J Rural Health ; 30(6): 860-869, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35802805

RESUMO

OBJECTIVE: Supporting Early Childhood Development (ECD) is an Australian national priority. Aboriginal children in Western Australia's Kimberley region have much higher rates of developmental concerns at school entry than non-Aboriginal children. We aimed to describe ECD practices in the participating service; document follow-up of identified developmental concerns; and identify barriers and enablers to incorporating ECD practices into clinic activity. DESIGN: Mixed-method design incorporating clinical audit and staff interviews. SETTING: An Aboriginal Community Controlled Health Service (ACCHS) in the Kimberley region. PARTICIPANTS: A total of 176 children receiving primary health care through the participating ACCHS; interviews with five ACCHS staff members. MAIN OUTCOME MEASURES: Frequency of developmental enquiry by age and domain; follow-up of identified developmental concerns; and barriers and enablers to ECD practices. RESULTS: Developmental enquiry was documented for 114 of 176 eligible children (65%), including in 80% of ACCHS child health assessments. Standardised ECD assessments were less common. Staff were aware of the importance of developmental enquiry, however, barriers to increasing ECD practices included a lack of resources and structured staff education, time pressures and a lack of role clarity between the ACCHS and government community health clinic. CONCLUSIONS: This study provides insight into ECD practices in an ACCHS setting, highlighting the potential of primary health care to have an enhanced role in ECD if appropriate systems, training and tools are provided. A lack of role clarity across services, combined with poor communication between services, creates a potential risk for missed opportunities to support ECD.


Assuntos
Serviços de Saúde do Indígena , Havaiano Nativo ou Outro Ilhéu do Pacífico , Criança , Humanos , Pré-Escolar , Austrália , Serviços de Saúde Comunitária , Desenvolvimento Infantil
4.
Med J Aust ; 211(1): 19-23, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30860606

RESUMO

OBJECTIVE: To describe the frequencies of acute kidney injury (AKI) and of associated diagnoses in Indigenous people in a remote Western Australian region. DESIGN: Retrospective population-based study of AKI events confirmed by changes in serum creatinine levels. SETTING, PARTICIPANTS: Aboriginal and Torres Strait Islander residents of the Kimberley region of Western Australia, aged 15 years or more and without end-stage kidney disease, for whom AKI between 1 June 2009 and 30 May 2016 was confirmed by an acute rise in serum creatinine levels. MAIN OUTCOME MEASURES: Age-specific AKI rates; principal and other diagnoses. RESULTS: 324 AKI events in 260 individuals were recorded; the median age of patients was 51.8 years (IQR, 43.9-61.0 years), and 176 events (54%) were in men. The overall AKI rate was 323 events (95% CI, 281-367) per 100 000 population; 92 events (28%) were in people aged 15-44 years. 52% of principal diagnoses were infectious in nature, including pneumonia (12% of events), infections of the skin and subcutaneous tissue (10%), and urinary tract infections (7.7%). 80 events (34%) were detected on or before the date of admission; fewer than one-third of discharge summaries (61 events, 28%) listed AKI as a primary or other diagnosis. CONCLUSION: The age distribution of AKI events among Indigenous Australians in the Kimberley was skewed to younger groups than in the national data on AKI. Infectious conditions were common in patients, underscoring the significance of environmental determinants of health. Primary care services can play an important role in preventing community-acquired AKI; applying pathology-based criteria could improve the detection of AKI.


Assuntos
Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etnologia , Havaiano Nativo ou Outro Ilhéu do Pacífico , Injúria Renal Aguda/fisiopatologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Creatinina/sangue , Feminino , Taxa de Filtração Glomerular , Humanos , Povos Indígenas , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Distribuição por Sexo , Austrália Ocidental/epidemiologia , Adulto Jovem
5.
BMC Public Health ; 19(1): 568, 2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-31088427

RESUMO

BACKGROUND: Unintended pregnancies are associated with poorer obstetric outcomes and are sometimes measured at a population level as a surrogate marker for reproductive autonomy and access to health services, including contraception. Aboriginal Australians face many disparities in health outcomes, including in reproductive health and antenatal care. We aimed to explore the formation and expression of pregnancy intentions in an Aboriginal population to inform health service improvements. METHODS: Semi-structured interviews were conducted with 27 remote-dwelling Aboriginal women, aged 18-49 years. Content analysis was conducted; key themes were discussed with groups of women from participating communities to refine interpretation. RESULTS: Most (19/27) participants expressed pregnancy intentions congruent with reported contraceptive behaviour while eight expressed ambivalent or uncertain intentions. Intentions were shaped by traditional kinship practices, reproductive autonomy and desired family formation. Younger women tended to aspire to smaller family sizes than older women and support was expressed for the postponement of first pregnancy to achieve other life goals. Women in these communities hold strong traditional beliefs, including regarding conception, but did not use traditional methods of contraception in place of modern methods. Reproductive coercion, in the form of pressure to fall pregnant, was recognised as an important issue by women in the community. CONCLUSION: Consultation strategies that promote rapport, allow space for uncertainty and are inclusive of important personal and cultural contexts are likely to improve shared understanding of pregnancy intention. Universal screening for reproductive coercion and broad counselling on contraceptive options (including discrete methods) may reduce unmet need for contraception. Community approaches supporting reproductive autonomy that is inclusive of men, and enhanced educational and occupational opportunities for young women are needed.


Assuntos
Comportamento Contraceptivo/psicologia , Características da Família , Havaiano Nativo ou Outro Ilhéu do Pacífico/psicologia , Gravidez não Planejada/psicologia , População Rural , Adolescente , Adulto , Austrália , Coerção , Anticoncepção/métodos , Anticoncepção/psicologia , Serviços de Planejamento Familiar , Feminino , Humanos , Intenção , Pessoa de Meia-Idade , Gravidez , Pesquisa Qualitativa , Adulto Jovem
6.
Nucleic Acids Res ; 44(D1): D646-53, 2016 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-26578582

RESUMO

The Pseudomonas Genome Database (http://www.pseudomonas.com) is well known for the application of community-based annotation approaches for producing a high-quality Pseudomonas aeruginosa PAO1 genome annotation, and facilitating whole-genome comparative analyses with other Pseudomonas strains. To aid analysis of potentially thousands of complete and draft genome assemblies, this database and analysis platform was upgraded to integrate curated genome annotations and isolate metadata with enhanced tools for larger scale comparative analysis and visualization. Manually curated gene annotations are supplemented with improved computational analyses that help identify putative drug targets and vaccine candidates or assist with evolutionary studies by identifying orthologs, pathogen-associated genes and genomic islands. The database schema has been updated to integrate isolate metadata that will facilitate more powerful analysis of genomes across datasets in the future. We continue to place an emphasis on providing high-quality updates to gene annotations through regular review of the scientific literature and using community-based approaches including a major new Pseudomonas community initiative for the assignment of high-quality gene ontology terms to genes. As we further expand from thousands of genomes, we plan to provide enhancements that will aid data visualization and analysis arising from whole-genome comparative studies including more pan-genome and population-based approaches.


Assuntos
Bases de Dados Genéticas , Genoma Bacteriano , Anotação de Sequência Molecular , Pseudomonas/genética , Proteínas de Bactérias/análise , Proteínas de Bactérias/química , Farmacorresistência Bacteriana/genética , Ontologia Genética , Ilhas Genômicas , Internet , Pseudomonas/efeitos dos fármacos , Pseudomonas/patogenicidade , Fatores de Virulência
8.
Med J Aust ; 205(1): 21-5, 2016 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-27362683

RESUMO

OBJECTIVE: To assess the use, effectiveness and acceptance of prescribed contraception in three remote Western Australian Aboriginal communities. PARTICIPANTS AND DESIGN: Mixed method study, including retrospective file review of contraception methods for 566 regular female Aboriginal patients, 1 November 2010 - 1 September 2014, and semi-structured interviews with 20 Aboriginal women. SETTING: Primary care clinics in three remote Aboriginal communities. MAIN OUTCOME MEASURES: Number of episodes of contraceptive use, effectiveness and continuation rates of prescribed contraceptive use; personal experiences, attitudes towards and beliefs about contraception options. RESULTS: 34% of women had used contraception, ranging from 15% of women aged younger than 15 years to 55% of women aged 15-19 years. The most common forms of contraception at the census date were long-acting reversible contraceptives (LARCs): 77% of women using contraception had an etonogestrel implant and 7% had depot medroxyprogesterone. Etonogestrel continuation rates at 1, 2 and 3 years were 87% (95% CI, 81-92%), 72% (95% CI, 64-78%) and 51% (95% CI, 41-60%) respectively. Medroxyprogesterone depot continuation at one year was only 14% (95% CI, 8-22%). Social acceptance of the etonogestrel implant was high; no concerns were raised about stigma or unwanted attention related to implant use. CONCLUSION: The high uptake of LARCs in these communities is consistent with international recommendations about contraception use. High acceptability was reflected in excellent continuation rates. Service delivery models that use community engagement and capacity building are recommended for broadening the focus of sexual health beyond sexually transmitted disease detection and management, giving priority to the reproductive rights and unmet needs of Aboriginal women.


Assuntos
Anticoncepcionais Femininos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Adolescente , Adulto , Austrália/epidemiologia , Criança , Implantes de Medicamento , Feminino , Humanos , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Estudos Retrospectivos , Adulto Jovem
9.
Antonie Van Leeuwenhoek ; 108(3): 765-81, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26179278

RESUMO

The phylum Chlamydiae contains nine ecologically and genetically diverse families all placed within a single order. In this work, we have completed a comprehensive comparative analysis of 36 sequenced Chlamydiae genomes in order to identify shared molecular characteristics, namely conserved signature insertions/deletions (CSIs) and conserved signature proteins (CSPs), which can serve as distinguishing characteristics of supra-familial clusters within the phylum Chlamydiae. Our analysis has led to the identification of 32 CSIs which are specific to clusters within the phylum Chlamydiae at various phylogenetic depths. Importantly, 17 CSIs and 98 CSPs were found to be specific for the family Chlamydiaceae while another 3 CSI variants and 15 CSPs were specific for a grouping of the families Criblamydiaceae, Parachlamydiaceae, Simkaniaceae and Waddliaceae. These two clusters were also found to be distinguishable in 16S rRNA based phylogenetic trees, concatenated protein based phylogenetic trees, character compatibility based phylogenetic analyses, and on the basis of 16S rRNA gene sequence identity and average amino acid identity values. On the basis of the identified molecular characteristics, branching in phylogenetic trees, and the genetic distance between the two clusters within the phylum Chlamydiae we propose a division of the class Chlamydiia into two orders: an emended order Chlamydiales, containing the family Chlamydiaceae and the closely related Candidatus family Clavichlamydiaceae, and the novel order Parachlamydiales ord. nov. containing the families Parachlamydiaceae, Simkaniaceae and Waddliaceae and the Candidatus families Criblamydiaceae, Parilichlamydiaceae, Piscichlamydiaceae, and Rhabdochlamydiaceae. We also include a brief discussion of the reunification of the genera Chlamydia and Chlamydophila.


Assuntos
Chlamydiales/classificação , Chlamydiales/genética , Variação Genética , Proteínas de Bactérias/genética , Análise por Conglomerados , Biologia Computacional , Sequência Conservada , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Genoma Bacteriano , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
10.
Med J Aust ; 201(6): 343-6, 2014 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-25222459

RESUMO

OBJECTIVES: To identify cases of hepatitis B infection after vaccination in Kimberley residents and determine maternal serostatus as a potential indicator of mode of transmission. DESIGN AND PARTICIPANTS: Retrospective review of Kimberley residents with notified hepatitis B infection using records of vaccination history and child and maternal serology. MAIN OUTCOME MEASURES: Confirmed cases of hepatitis B infection after vaccination; chronic infection in cases of hepatitis B infection after vaccination; maternal serostatus in confirmed cases of hepatitis B infection after vaccination. RESULTS: From 1 January 1984 to 31 March 2011, we identified 17 cases of Aboriginal residents with hepatitis B infection after vaccination (10 chronic infections, five not defined and two cleared). In six patients, maternal chronic infection had been identified at some stage, raising the possibility of vertical transmission. In seven patients, maternal serology or evidence of subsequent acquisition suggested that horizontal transmission and therefore vaccination failure was likely. For four patients, there was inadequate information to assess possible mode of transmission. CONCLUSIONS: Hepatitis B infection after full vaccination is not limited to children of mothers with active infection. Further undiagnosed infections in the Kimberley are likely, and active monitoring to detect the extent and likely cause of hepatitis B infection in vaccinated children is needed. In children where vertical transmission is a risk, prospective follow-up is warranted.


Assuntos
Vacinas contra Hepatite B , Hepatite B/prevenção & controle , Hepatite B/transmissão , Transmissão Vertical de Doenças Infecciosas , Havaiano Nativo ou Outro Ilhéu do Pacífico , Adolescente , Criança , Estudos de Coortes , Hepatite B/sangue , Anticorpos Anti-Hepatite B/sangue , Antígenos da Hepatite B/sangue , Humanos , Mães , Estudos Retrospectivos , Austrália Ocidental , Adulto Jovem
11.
Biomech Model Mechanobiol ; 23(3): 793-808, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38361082

RESUMO

Finite element (FE) simulations of the brain undergoing neurosurgical procedures present us with the great opportunity to better investigate, understand, and optimize surgical techniques and equipment. FE models provide access to data such as the stress levels within the brain that would otherwise be inaccessible with the current medical technology. Brain retraction is often a dangerous but necessary part of neurosurgery, and current research focuses on minimizing trauma during the procedure. In this work, we present a simulation-based comparison of different types of retraction mechanisms. We focus on traditional spatulas and tubular retractors. Our results show that tubular retractors result in lower average predicted stresses, especially in the subcortical structures and corpus callosum. Additionally, we show that changing the location of retraction can greatly affect the predicted stress results. As the model predictions highly depend on the material model and parameters used for simulations, we also investigate the importance of using region-specific hyperelastic and viscoelastic material parameters when modelling a three-dimensional human brain during retraction. Our investigations demonstrate how FE simulations in neurosurgical techniques can provide insight to surgeons and medical device manufacturers. They emphasize how further work into this direction could greatly improve the management and prevention of injury during surgery. Additionally, we show the importance of modelling the human brain with region-dependent parameters in order to provide useful predictions for neurosurgical procedures.


Assuntos
Encéfalo , Análise de Elementos Finitos , Estresse Mecânico , Humanos , Encéfalo/fisiologia , Simulação por Computador , Elasticidade , Procedimentos Neurocirúrgicos , Modelos Biológicos
12.
Science ; 384(6703): eadl0370, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38935708

RESUMO

Innate lymphoid cells (ILCs) and adaptive T lymphocytes promote tissue homeostasis and protective immune responses. Their production depends on the transcription factor GATA3, which is further elevated specifically in ILC2s and T helper 2 cells to drive type-2 immunity during tissue repair, allergic disorders, and anti-helminth immunity. The control of this crucial up-regulation is poorly understood. Using CRISPR screens in ILCs we identified previously unappreciated myocyte-specific enhancer factor 2d (Mef2d)-mediated regulation of GATA3-dependent type-2 lymphocyte differentiation. Mef2d-deletion from ILC2s and/or T cells specifically protected against an allergen lung challenge. Mef2d repressed Regnase-1 endonuclease expression to enhance IL-33 receptor production and IL-33 signaling and acted downstream of calcium-mediated signaling to translocate NFAT1 to the nucleus to promote type-2 cytokine-mediated immunity.


Assuntos
Fator de Transcrição GATA3 , Imunidade Inata , Interleucina-33 , Fatores de Transcrição MEF2 , Fatores de Transcrição NFATC , Pneumonia , Células Th2 , Animais , Camundongos , Fatores de Transcrição MEF2/metabolismo , Fatores de Transcrição MEF2/genética , Células Th2/imunologia , Interleucina-33/metabolismo , Fatores de Transcrição NFATC/metabolismo , Pneumonia/imunologia , Fator de Transcrição GATA3/metabolismo , Fator de Transcrição GATA3/genética , Camundongos Endogâmicos C57BL , Diferenciação Celular , Sinalização do Cálcio , Hipersensibilidade/imunologia , Pulmão/imunologia , Alérgenos/imunologia , Linfócitos/imunologia , Proteína 1 Semelhante a Receptor de Interleucina-1
13.
Microb Genom ; 10(6)2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38860884

RESUMO

As public health laboratories expand their genomic sequencing and bioinformatics capacity for the surveillance of different pathogens, labs must carry out robust validation, training, and optimization of wet- and dry-lab procedures. Achieving these goals for algorithms, pipelines and instruments often requires that lower quality datasets be made available for analysis and comparison alongside those of higher quality. This range of data quality in reference sets can complicate the sharing of sub-optimal datasets that are vital for the community and for the reproducibility of assays. Sharing of useful, but sub-optimal datasets requires careful annotation and documentation of known issues to enable appropriate interpretation, avoid being mistaken for better quality information, and for these data (and their derivatives) to be easily identifiable in repositories. Unfortunately, there are currently no standardized attributes or mechanisms for tagging poor-quality datasets, or datasets generated for a specific purpose, to maximize their utility, searchability, accessibility and reuse. The Public Health Alliance for Genomic Epidemiology (PHA4GE) is an international community of scientists from public health, industry and academia focused on improving the reproducibility, interoperability, portability, and openness of public health bioinformatic software, skills, tools and data. To address the challenges of sharing lower quality datasets, PHA4GE has developed a set of standardized contextual data tags, namely fields and terms, that can be included in public repository submissions as a means of flagging pathogen sequence data with known quality issues, increasing their discoverability. The contextual data tags were developed through consultations with the community including input from the International Nucleotide Sequence Data Collaboration (INSDC), and have been standardized using ontologies - community-based resources for defining the tag properties and the relationships between them. The standardized tags are agnostic to the organism and the sequencing technique used and thus can be applied to data generated from any pathogen using an array of sequencing techniques. The tags can also be applied to synthetic (lab created) data. The list of standardized tags is maintained by PHA4GE and can be found at https://github.com/pha4ge/contextual_data_QC_tags. Definitions, ontology IDs, examples of use, as well as a JSON representation, are provided. The PHA4GE QC tags were tested, and are now implemented, by the FDA's GenomeTrakr laboratory network as part of its routine submission process for SARS-CoV-2 wastewater surveillance. We hope that these simple, standardized tags will help improve communication regarding quality control in public repositories, in addition to making datasets of variable quality more easily identifiable. Suggestions for additional tags can be submitted to PHA4GE via the New Term Request Form in the GitHub repository. By providing a mechanism for feedback and suggestions, we also expect that the tags will evolve with the needs of the community.


Assuntos
Biologia Computacional , Saúde Pública , Controle de Qualidade , Humanos , Biologia Computacional/métodos , Disseminação de Informação/métodos , Reprodutibilidade dos Testes , Anotação de Sequência Molecular/métodos , Genômica/métodos , Software
14.
ArXiv ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38764594

RESUMO

The COVID-19 pandemic led to a large global effort to sequence SARS-CoV-2 genomes from patient samples to track viral evolution and inform public health response. Millions of SARS-CoV-2 genome sequences have been deposited in global public repositories. The Canadian COVID-19 Genomics Network (CanCOGeN - VirusSeq), a consortium tasked with coordinating expanded sequencing of SARS-CoV-2 genomes across Canada early in the pandemic, created the Canadian VirusSeq Data Portal, with associated data pipelines and procedures, to support these efforts. The goal of VirusSeq was to allow open access to Canadian SARS-CoV-2 genomic sequences and enhanced, standardized contextual data that were unavailable in other repositories and that meet FAIR standards (Findable, Accessible, Interoperable and Reusable). In addition, the Portal data submission pipeline contains data quality checking procedures and appropriate acknowledgement of data generators that encourages collaboration. From inception to execution, the portal was developed with a conscientious focus on strong data governance principles and practices. Extensive efforts ensured a commitment to Canadian privacy laws, data security standards, and organizational processes. This Portal has been coupled with other resources like Viral AI and was further leveraged by the Coronavirus Variants Rapid Response Network (CoVaRR-Net) to produce a suite of continually updated analytical tools and notebooks. Here we highlight this Portal, including its contextual data not available elsewhere, and the 'Duotang', a web platform that presents key genomic epidemiology and modeling analyses on circulating and emerging SARS-CoV-2 variants in Canada. Duotang presents dynamic changes in variant composition of SARS-CoV-2 in Canada and by province, estimates variant growth, and displays complementary interactive visualizations, with a text overview of the current situation. The VirusSeq Data Portal and Duotang resources, alongside additional analyses and resources computed from the Portal (COVID-MVP, CoVizu), are all open-source and freely available. Together, they provide an updated picture of SARS-CoV-2 evolution to spur scientific discussions, inform public discourse, and support communication with and within public health authorities. They also serve as a framework for other jurisdictions interested in open, collaborative sequence data sharing and analyses.

15.
Mol Microbiol ; 86(6): 1404-23, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23078142

RESUMO

The interaction of Cryptococcus neoformans with phagocytic cells of the innate immune system is a key step in disseminated disease leading to meningoencephalitis in immunocompromised individuals. Transcriptional profiling of cryptococcal cells harvested from cell culture medium or from macrophages found differential expression of metabolic and other functions during fungal adaptation to the intracellular environment. We focused on the ACL1 gene for ATP-citrate lyase, which converts citrate to acetyl-CoA, because this gene showed elevated transcript levels in macrophages and because of the importance of acetyl-CoA as a central metabolite. Mutants lacking ACL1 showed delayed growth on medium containing glucose, reduced cellular levels of acetyl-CoA, defective production of virulence factors, increased susceptibility to the antifungal drug fluconazole and decreased survival within macrophages. Importantly, acl1 mutants were unable to cause disease in a murine inhalation model, a phenotype that was more extreme than other mutants with defects in acetyl-CoA production (e.g. an acetyl-CoA synthetase mutant). Loss of virulence is likely due to perturbation of critical physiological interconnections between virulence factor expression and metabolism in C. neoformans. Phylogenetic analysis and structural modelling of cryptococcal Acl1 identified three indels unique to fungal protein sequences; these differences may provide opportunities for the development of pathogen-specific inhibitors.


Assuntos
ATP Citrato (pro-S)-Liase/deficiência , Acetilcoenzima A/metabolismo , Cryptococcus neoformans/metabolismo , Cryptococcus neoformans/patogenicidade , Fatores de Virulência/metabolismo , ATP Citrato (pro-S)-Liase/metabolismo , Sequência de Aminoácidos , Animais , Linhagem Celular , Ácido Cítrico/metabolismo , Criptococose/microbiologia , Criptococose/patologia , Cryptococcus neoformans/enzimologia , Cryptococcus neoformans/genética , Meios de Cultura/química , Modelos Animais de Doenças , Glucose/metabolismo , Mutação INDEL , Macrófagos/imunologia , Macrófagos/microbiologia , Camundongos , Viabilidade Microbiana , Modelos Moleculares , Dados de Sequência Molecular , Filogenia , Homologia de Sequência de Aminoácidos , Virulência
16.
Eukaryot Cell ; 11(2): 109-18, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22140231

RESUMO

The basidiomycete fungus Cryptococcus neoformans infects humans via inhalation of desiccated yeast cells or spores from the environment. In the absence of effective immune containment, the initial pulmonary infection often spreads to the central nervous system to result in meningoencephalitis. The fungus must therefore make the transition from the environment to different mammalian niches that include the intracellular locale of phagocytic cells and extracellular sites in the lung, bloodstream, and central nervous system. Recent studies provide insights into mechanisms of adaptation during this transition that include the expression of antiphagocytic functions, the remodeling of central carbon metabolism, the expression of specific nutrient acquisition systems, and the response to hypoxia. Specific transcription factors regulate these functions as well as the expression of one or more of the major known virulence factors of C. neoformans. Therefore, virulence factor expression is to a large extent embedded in the regulation of a variety of functions needed for growth in mammalian hosts. In this regard, the complex integration of these processes is reminiscent of the master regulators of virulence in bacterial pathogens.


Assuntos
Cryptococcus neoformans/fisiologia , Cryptococcus neoformans/patogenicidade , Regulação Fúngica da Expressão Gênica , Interações Hospedeiro-Patógeno , Adaptação Fisiológica , Animais , Humanos , Ferro/metabolismo , Mamíferos , Virulência , Fatores de Virulência/genética , Fatores de Virulência/metabolismo
17.
mSystems ; 8(2): e0128422, 2023 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-36847566

RESUMO

Large, open-source DNA sequence databases have been generated, in part, through the collection of microbial pathogens by swabbing surfaces in built environments. Analyzing these data in aggregate through public health surveillance requires digitization of the complex, domain-specific metadata that are associated with the swab site locations. However, the swab site location information is currently collected in a single, free-text, "isolation source", field-promoting generation of poorly detailed descriptions with various word order, granularity, and linguistic errors, making automation difficult and reducing machine-actionability. We assessed 1,498 free-text swab site descriptions that were generated during routine foodborne pathogen surveillance. The lexicon of free-text metadata was evaluated to determine the informational facets and the quantity of unique terms used by data collectors. Open Biological Ontologies (OBO) Foundry libraries were used to develop hierarchical vocabularies that are connected with logical relationships to describe swab site locations. 5 informational facets that were described by 338 unique terms were identified via content analysis. Term hierarchy facets were developed, as were statements (called axioms) about how the entities within these five domains are related. The schema developed through this study has been integrated into a publicly available pathogen metadata standard, facilitating ongoing surveillance and investigations. The One Health Enteric Package was available at NCBI BioSample, beginning in 2022. The collective use of metadata standards increases the interoperability of DNA sequence databases and enables large-scale approaches to data sharing and artificial intelligence as well as big-data solutions to food safety. IMPORTANCE The regular analysis of whole-genome sequence data in collections such as NCBI's Pathogen Detection Database is used by many public health organizations to detect outbreaks of infectious disease. However, isolate metadata in these databases are often incomplete and of poor quality. These complex, raw metadata must often be reorganized and manually formatted for use in aggregate analyses. These processes are inefficient and time-consuming, increasing the interpretative labor needed by public health groups to extract actionable information. The future use of open genomic epidemiology networks will be supported through the development of an internationally applicable vocabulary system with which swab site locations can be described.


Assuntos
Doenças Transmissíveis , Bases de Dados de Ácidos Nucleicos , Humanos , Metadados , Inteligência Artificial , Genômica
18.
BMJ Open ; 13(2): e066418, 2023 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-36750286

RESUMO

OBJECTIVES: COVID-19 research has significantly contributed to pandemic response and the enhancement of public health capacity. COVID-19 data collected by provincial/territorial health authorities in Canada are valuable for research advancement yet not readily available to the public, including researchers. To inform developments in public health data-sharing in Canada, we explored Canadians' opinions of public health authorities sharing deidentified individual-level COVID-19 data publicly. DESIGN/SETTING/INTERVENTIONS/OUTCOMES: A national cross-sectional survey was administered in Canada in March 2022, assessing Canadians' opinions on publicly sharing COVID-19 datatypes. Market research firm Léger was employed for recruitment and data collection. PARTICIPANTS: Anyone greater than or equal to 18 years and currently living in Canada. RESULTS: 4981 participants completed the survey with a 92.3% response rate. 79.7% were supportive of provincial/territorial authorities publicly sharing deidentified COVID-19 data, while 20.3% were hesitant/averse/unsure. Datatypes most supported for being shared publicly were symptoms (83.0% in support), geographical region (82.6%) and COVID-19 vaccination status (81.7%). Datatypes with the most aversion were employment sector (27.4% averse), postal area (26.7%) and international travel history (19.7%). Generally supportive Canadians were characterised as being ≥50 years, with higher education, and being vaccinated against COVID-19 at least once. Vaccination status was the most influential predictor of data-sharing opinion, with respondents who were ever vaccinated being 4.20 times more likely (95% CI 3.21 to 5.48, p=0.000) to be generally supportive of data-sharing than those unvaccinated. CONCLUSIONS: These findings suggest that the Canadian public is generally favourable to deidentified data-sharing. Identifying factors that are likely to improve attitudes towards data-sharing are useful to stakeholders involved in data-sharing initiatives, such as public health agencies, in informing the development of public health communication and data-sharing policies. As Canada progresses through the COVID-19 pandemic, and with limited testing and reporting of COVID-19 data, it is essential to improve deidentified data-sharing given the public's general support for these efforts.


Assuntos
COVID-19 , Humanos , Estudos Transversais , Opinião Pública , Pandemias , Vacinas contra COVID-19 , Canadá
19.
Microb Genom ; 9(12)2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38085797

RESUMO

Fast, efficient public health actions require well-organized and coordinated systems that can supply timely and accurate knowledge. Public databases of pathogen genomic data, such as the International Nucleotide Sequence Database Collaboration (INSDC), have become essential tools for efficient public health decisions. However, these international resources began primarily for academic purposes, rather than for surveillance or interventions. Now, queries need to access not only the whole genomes of multiple pathogens but also make connections using robust contextual metadata to identify issues of public health relevance. Databases that over time developed a patchwork of submission formats and requirements need to be consistently organized and coordinated internationally to allow effective searches.To help resolve these issues, we propose a common pathogen data structure called the Pathogen Data Object Model (DOM) that will formalize the minimum pieces of sequence data and contextual data necessary for general public health uses, while recognizing that submitters will likely withhold a wide range of non-public contextual data. Further, we propose contributors use the Pathogen DOM for all pathogen submissions (bacterial, viral, fungal, and parasites), which will simplify data submissions and provide a consistent and transparent data structure for downstream data analyses. We also highlight how improved submission tools can support the Pathogen DOM, offering users additional easy-to-use methods to ensure this structure is followed.


Assuntos
Nucleotídeos , Saúde Pública , Sequência de Bases , Genômica/métodos , Bases de Dados de Ácidos Nucleicos
20.
Microb Genom ; 9(1)2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36748616

RESUMO

Pathogen genomics is a critical tool for public health surveillance, infection control, outbreak investigations as well as research. In order to make use of pathogen genomics data, they must be interpreted using contextual data (metadata). Contextual data include sample metadata, laboratory methods, patient demographics, clinical outcomes and epidemiological information. However, the variability in how contextual information is captured by different authorities and how it is encoded in different databases poses challenges for data interpretation, integration and their use/re-use. The DataHarmonizer is a template-driven spreadsheet application for harmonizing, validating and transforming genomics contextual data into submission-ready formats for public or private repositories. The tool's web browser-based JavaScript environment enables validation and its offline functionality and local installation increases data security. The DataHarmonizer was developed to address the data sharing needs that arose during the COVID-19 pandemic, and was used by members of the Canadian COVID Genomics Network (CanCOGeN) to harmonize SARS-CoV-2 contextual data for national surveillance and for public repository submission. In order to support coordination of international surveillance efforts, we have partnered with the Public Health Alliance for Genomic Epidemiology to also provide a template conforming to its SARS-CoV-2 contextual data specification for use worldwide. Templates are also being developed for One Health and foodborne pathogens. Overall, the DataHarmonizer tool improves the effectiveness and fidelity of contextual data capture as well as its subsequent usability. Harmonization of contextual information across authorities, platforms and systems globally improves interoperability and reusability of data for concerted public health and research initiatives to fight the current pandemic and future public health emergencies. While initially developed for the COVID-19 pandemic, its expansion to other data management applications and pathogens is already underway.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , Pandemias , SARS-CoV-2/genética , Canadá , Genômica/métodos
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