Specialized or secondary metabolites are small molecules of biological origin, often showing potent biological activities with applications in agriculture, engineering and medicine. Usually, the biosynthesis of these natural products is governed by sets of co-regulated and physically clustered genes known as biosynthetic gene clusters (BGCs). To share information about BGCs in a standardized and machine-readable way, the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard and repository was initiated in 2015. Since its conception, MIBiG has been regularly updated to expand data coverage and remain up to date with innovations in natural product research. Here, we describe MIBiG version 4.0, an extensive update to the data repository and the underlying data standard. In a massive community annotation effort, 267 contributors performed 8304 edits, creating 557 new entries and modifying 590 existing entries, resulting in a new total of 3059 curated entries in MIBiG. Particular attention was paid to ensuring high data quality, with automated data validation using a newly developed custom submission portal prototype, paired with a novel peer-reviewing model. MIBiG 4.0 also takes steps towards a rolling release model and a broader involvement of the scientific community. MIBiG 4.0 is accessible online at https://mibig.secondarymetabolites.org/.
- Klíčová slova
- penetrační testování,
- MeSH
- důvěrnost informací trendy MeSH
- informační systémy organizace a řízení MeSH
- laboratorní medicína přístrojové vybavení MeSH
- lékařská počítačová informatika * trendy MeSH
- lidé MeSH
- počítačová simulace * trendy MeSH
- přístup k informacím MeSH
- zabezpečení počítačových systémů přístrojové vybavení trendy zákonodárství a právo MeSH
- Check Tag
- lidé MeSH
Genetic variation occurring within conserved functional protein domains warrants special attention when examining DNA variation in the context of disease causation. Here we introduce a resource, freely available at www.prot2hg.com, that addresses the question of whether a particular variant falls onto an annotated protein domain and directly translates chromosomal coordinates onto protein residues. The tool can perform a multiple-site query in a simple way, and the whole dataset is available for download as well as incorporated into our own accessible pipeline. To create this resource, National Center for Biotechnology Information protein data were retrieved using the Entrez Programming Utilities. After processing all human protein domains, residue positions were reverse translated and mapped to the reference genome hg19 and stored in a MySQL database. In total, 760 487 protein domains from 42 371 protein models were mapped to hg19 coordinates and made publicly available for search or download (www.prot2hg.com). In addition, this annotation was implemented into the genomics research platform GENESIS in order to query nearly 8000 exomes and genomes of families with rare Mendelian disorders (tgp-foundation.org). When applied to patient genetic data, we found that rare (<1%) variants in the Genome Aggregation Database were significantly more annotated onto a protein domain in comparison to common (>1%) variants. Similarly, variants described as pathogenic or likely pathogenic in ClinVar were more likely to be annotated onto a domain. In addition, we tested a dataset consisting of 60 causal variants in a cohort of patients with epileptic encephalopathy and found that 71% of them (43 variants) were propagated onto protein domains. In summary, we developed a resource that annotates variants in the coding part of the genome onto conserved protein domains in order to increase variant prioritization efficiency.Database URL: www.prot2hg.com.
- MeSH
- anotace sekvence metody MeSH
- data mining metody MeSH
- databáze genetické * MeSH
- datové kurátorství metody MeSH
- genetická variace * MeSH
- genom lidský genetika MeSH
- genomika metody MeSH
- internet MeSH
- lidé MeSH
- proteinové domény genetika MeSH
- proteiny chemie genetika metabolismus MeSH
- výpočetní biologie metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
With the advent of precision and genomic medicine, a critical issue is whether a disease gene variant is pathogenic or benign. Such is the case for the three autosomal dominant acute hepatic porphyrias (AHPs), including acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria, each resulting from the half-normal enzymatic activities of hydroxymethylbilane synthase, coproporphyrinogen oxidase, and protoporphyrinogen oxidase, respectively. To date, there is no public database that documents the likely pathogenicity of variants causing the porphyrias, and more specifically, the AHPs with biochemically and clinically verified information. Therefore, an international collaborative with the European Porphyria Network and the National Institutes of Health/National Center for Advancing Translational Sciences/National Institute of Diabetes and Digestive and Kidney Diseases (NIH/NCATS/NIDDK)-sponsored Porphyrias Consortium of porphyria diagnostic experts is establishing an online database that will collate biochemical and clinical evidence verifying the pathogenicity of the published and newly identified variants in the AHP-causing genes. The overall goal of the International Porphyria Molecular Diagnostic Collaborative is to determine the pathogenic and benign variants for all eight porphyrias. Here we describe the overall objectives and the initial efforts to validate pathogenic and benign variants in the respective heme biosynthetic genes causing the AHPs.
- MeSH
- akutní intermitentní porfyrie genetika patofyziologie MeSH
- databáze faktografické MeSH
- datové kurátorství metody MeSH
- jaterní porfyrie genetika patofyziologie MeSH
- lidé MeSH
- molekulární patologie MeSH
- porfobilinogensynthasa nedostatek genetika MeSH
- porfyrie genetika patofyziologie MeSH
- virulence genetika MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Spojené státy americké MeSH
Background: The driving force for information and communication technology in healthcare has been directed towards better-coordinated care but high cost and time consumption in addition to difficulties with cooperation with resident practitioners has hampered progress. Therefore, due to the underestimation of difficulties to manage national eHealth activities, the potential of eHealth in Europe is still to be realized. Methods: An evaluation of the national eHealth in Slovenia grounded on open platform theory based organizational design principles for eHealth platforms has been conducted. We used a running use case of an eDiabetes digital health intervention as a potential new central service of the national eHealth platform. We discussed all the design principles and also constructed a questionnaire during the process to additionally help with the evaluation. Results: We have identified a gap that needs to be bridged in order for Slovenia to achieve all the benefits of an open eHealth platform that could become a strategic direction for the future. We constructed a questionnaire that is based on the open platform theory grounded design principles for open eHealth platforms which we used as a helping tool to perform the analysis. Conclusion: By evaluating the national eHealth in Slovenia against the open eHealth platform organizational design principles, we identified a gap that needs to be bridged to benefit from the positive effects of open eHealth platforms. Being open suggests participation, extension and growth both in terms of demand side users (e.g. patients and doctors) and supply side platform users (e.g. IT companies, HCPs etc.) Shortage of a business model is just one principle that still needs to be met in addition to several others. With this, Slovenia can ground its national eHealth vision and strategy on the results of this analysis.
- Klíčová slova
- elektronické zdravotnictví, e-health,
- MeSH
- elektronické zdravotní záznamy * MeSH
- lékařská počítačová informatika MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Geografické názvy
- Slovinsko MeSH
Environmental sequencing has greatly expanded our knowledge of micro-eukaryotic diversity and ecology by revealing previously unknown lineages and their distribution. However, the value of these data is critically dependent on the quality of the reference databases used to assign an identity to environmental sequences. Existing databases contain errors and struggle to keep pace with rapidly changing eukaryotic taxonomy, the influx of novel diversity, and computational challenges related to assembling the high-quality alignments and trees needed for accurate characterization of lineage diversity. EukRef (eukref.org) is an ongoing community-driven initiative that addresses these challenges by bringing together taxonomists with expertise spanning the eukaryotic tree of life and microbial ecologists, who use environmental sequence data to develop reliable reference databases across the diversity of microbial eukaryotes. EukRef organizes and facilitates rigorous mining and annotation of sequence data by providing protocols, guidelines, and tools. The EukRef pipeline and tools allow users interested in a particular group of microbial eukaryotes to retrieve all sequences belonging to that group from International Nucleotide Sequence Database Collaboration (INSDC) (GenBank, the European Nucleotide Archive [ENA], or the DNA DataBank of Japan [DDBJ]), to place those sequences in a phylogenetic tree, and to curate taxonomic and environmental information for the group. We provide guidelines to facilitate the process and to standardize taxonomic annotations. The final outputs of this process are (1) a reference tree and alignment, (2) a reference sequence database, including taxonomic and environmental information, and (3) a list of putative chimeras and other artifactual sequences. These products will be useful for the broad community as they become publicly available (at eukref.org) and are shared with existing reference databases.
- MeSH
- Ciliophora genetika MeSH
- databáze genetické MeSH
- datové kurátorství * MeSH
- Eukaryota klasifikace genetika MeSH
- fylogeneze * MeSH
- genetická variace * MeSH
- RNA ribozomální genetika MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
Součástí návrhu informačních systémů je vedle analýzy klinické domény i konstrukce aplikačního datového modelu. Přehledový článek nabízí popis dostupných referenčních modelů EN 13606 a HL7 RIM, jejich rozsah, základní vlastnosti i způsoby užití. Záměrem je sjednocení konceptuálního myšlení, usnadnění modelování klinické domény a v určitých případech snad realizace aplikačního modelu na základě některého z referenčních modelů. Taková aplikace je vždy snáze integrovatelná a propojitelná s ekosystémem zdravotnictví pomocí standardizovaných datových protokolů, které na referenční modely spoléhají. Článek se zamýšlí nad úskalími při použití modelů HL7 FHIR a DASTA jakožto referenčními modely pro aplikační modely. Ve výsledcích je popsána zkušenost s adaptací HL7 FHIR DSTU 1.0.2 jako aplikačním modelem.
- Klíčová slova
- datový model, referenční model, DASTA, EN 13606, HL7,
- MeSH
- informační systémy MeSH
- lékařská počítačová informatika MeSH
- šíření informací MeSH
- telemedicína metody MeSH
- využití lékařské informatiky MeSH
- Publikační typ
- přehledy MeSH
Realising the importance of assessing the quality of the biomolecular structures deposited in the Protein Data Bank (PDB), the Worldwide Protein Data Bank (wwPDB) partners established Validation Task Forces to obtain advice on the methods and standards to be used to validate structures determined by X-ray crystallography, nuclear magnetic resonance spectroscopy and three-dimensional electron cryo-microscopy. The resulting wwPDB validation pipeline is an integral part of the wwPDB OneDep deposition, biocuration and validation system. The wwPDB Validation Service webserver (https://validate.wwpdb.org) can be used to perform checks prior to deposition. Here, it is shown how validation metrics can be combined to produce an overall score that allows the ranking of macromolecular structures and domains in search results. The ValTrendsDB database provides users with a convenient way to access and analyse validation information and other properties of X-ray crystal structures in the PDB, including investigating trends in and correlations between different structure properties and validation metrics.
- MeSH
- databáze proteinů normy MeSH
- datové kurátorství MeSH
- elektronová kryomikroskopie MeSH
- internet * MeSH
- konformace proteinů * MeSH
- lidé MeSH
- makromolekulární látky chemie MeSH
- molekulární modely MeSH
- nukleární magnetická rezonance biomolekulární MeSH
- proteiny analýza chemie MeSH
- uživatelské rozhraní počítače * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- validační studie MeSH
