A multitude of factors contribute to complex diseases and can be measured with ‘omics’ methods. Databases facilitate data interpretation for underlying mechanisms. Here, we describe the Virtual Metabolic Human (VMH, www.vmh.life) database encapsulating current knowledge of human metabolism within five interlinked resources ‘Human metabolism’, ‘Gut microbiome’, ‘Disease’, ‘Nutrition’, and ‘ReconMaps’. The VMH captures 5180 unique metabolites, 17 730 unique reactions, 3695 human genes, 255 Mendelian diseases, 818 microbes, 632 685 microbial genes and 8790 food items. The VMH’s unique features are (i) the hosting of the metabolic reconstructions of human and gut microbes amenable for metabolic modeling; (ii) seven human metabolic maps for data visualization; (iii) a nutrition designer; (iv) a user-friendly webpage and application-programming interface to access its content; (v) user feedback option for community engagement and (vi) the connection of its entities to 57 other web resources. The VMH represents a novel, interdisciplinary database for data interpretation and hypothesis generation to the biomedical community.
2 June 2018 in npj Systems Biology and Applications
The development of computational approaches in systems biology has reached a state of maturity that allows their transition to systems medicine. Despite this progress, intuitive visualisation and context-dependent knowledge representation still present a major bottleneck. In this paper, we describe the Disease Maps Project, an effort towards a community-driven computationally readable comprehensive representation of disease mechanisms. We outline the key principles and the framework required for the success of this initiative, including use of best practices, standards and protocols. We apply a modular approach to ensure efficient sharing and reuse of resources for projects dedicated to specific diseases. Community-wide use of disease maps will accelerate the conduct of biomedical research and lead to new disease ontologies defined from mechanism-based disease endotypes rather than phenotypes.
We need to effectively combine the knowledge from surging literature with complex datasets to propose mechanistic models of SARS‐CoV‐2 infection, improving data interpretation and predicting key targets of intervention. Here, we describe a large‐scale community effort to build an open access, interoperable and computable repository of COVID‐19 molecular mechanisms. The COVID‐19 Disease Map (C19DMap) is a graphical, interactive representation of disease‐relevant molecular mechanisms linking many knowledge sources. Notably, it is a computational resource for graph‐based analyses and disease modelling. To this end, we established a framework of tools, platforms and guidelines necessary for a multifaceted community of biocurators, domain experts, bioinformaticians and computational biologists. The diagrams of the C19DMap, curated from the literature, are integrated with relevant interaction and text mining databases. We demonstrate the application of network analysis and modelling approaches by concrete examples to highlight new testable hypotheses. This framework helps to find signatures of SARS‐CoV‐2 predisposition, treatment response or prioritisation of drug candidates. Such an approach may help deal with new waves of COVID‐19 or similar pandemics in the long‐term perspective.
The Disease Maps Project builds on a network of scientific and clinical groups that exchange best practices, share information and develop systems biomedicine tools. The project aims for an integrated, highly curated and user-friendly platform for disease-related knowledge. The primary focus of disease maps is on interconnected signaling, metabolic and gene regulatory network pathways represented in standard formats. The involvement of domain experts ensures that the key disease hallmarks are covered and relevant, up-to-date knowledge is adequately represented. Expert-curated and computer readable, disease maps may serve as a compendium of knowledge, allow for data-supported hypothesis generation or serve as a scaffold for the generation of predictive mathematical models. This article summarizes the 2nd Disease Maps Community meeting, highlighting its important topics and outcomes. We outline milestones on the roadmap for the future development of disease maps, including creating and maintaining standardized disease maps; sharing parts of maps that encode common human disease mechanisms; providing technical solutions for complexity management of maps; and Web tools for in-depth exploration of such maps. A dedicated discussion was focused on mathematical modeling approaches, as one of the main goals of disease map development is the generation of mathematically interpretable representations to predict disease comorbidity or drug response and to suggest drug repositioning, altogether supporting clinical decisions.
Background: Molecular biology knowledge can be formalized and systematically represented in a computer-readable form as a comprehensive map of molecular interactions. There exist an increasing number of maps of molecular interactions containing detailed and step-wise description of various cell mechanisms. It is difficult to explore these large maps, to organize discussion of their content and to maintain them. Several efforts were recently made to combine these capabilities together in one environment, and NaviCell is one of them. Results: NaviCell is a web-based environment for exploiting large maps of molecular interactions, created in CellDesigner, allowing their easy exploration, curation and maintenance. It is characterized by a combination of three essential features: (1) efficient map browsing based on Google Maps; (2) semantic zooming for viewing different levels of details or of abstraction of the map and (3) integrated web-based blog for collecting community feedback. NaviCell can be easily used by experts in the field of molecular biology for studying molecular entities of interest in the context of signaling pathways and crosstalk between pathways within a global signaling network. NaviCell allows both exploration of detailed molecular mechanisms represented on the map and a more abstract view of the map up to a top-level modular representation. NaviCell greatly facilitates curation, maintenance and updating the comprehensive maps of molecular interactions in an interactive and user-friendly fashion due to an imbedded blogging system. Conclusions: NaviCell provides user-friendly exploration of large-scale maps of molecular interactions, thanks to Google Maps and WordPress interfaces, with which many users are already familiar. Semantic zooming which is used for navigating geographical maps is adopted for molecular maps in NaviCell, making any level of visualization readable. In addition, NaviCell provides a framework for community-based curation of maps.