BioThings Explorer: a query engine for a federated knowledge graph of biomedical APIs

Knowledge graphs are an increasingly common data structure for representing biomedical information. These knowledge graphs can easily represent heterogeneous types of information, and many algorithms and tools exist for querying and analyzing graphs. Biomedical knowledge graphs have been used in a variety of applications, including drug repurposing, identification of drug targets, prediction of drug side effects, and clinical decision support. Typically, knowledge graphs are constructed by centralization and integration of data from multiple disparate sources. Here, we describe BioThings Explorer, an application that can query a virtual, federated knowledge graph derived from the aggregated information in a network of biomedical web services. BioThings Explorer leverages semantically precise annotations of the inputs and outputs for each resource, and automates the chaining of web service calls to execute multi-step graph queries. Because there is no large, centralized knowledge graph to maintain, BioThing Explorer is distributed as a lightweight application that dynamically retrieves information at query time. More information can be found at https://explorer.biothings.io, and code is available at https://github.com/biothings/biothings_explorer

COVID19 Disease Map, a computational knowledge repository of virus-host interaction mechanisms.

Funder: Bundesministerium für Bildung und ForschungFunder: Bundesministerium für Bildung und Forschung (BMBF)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

Extending WikiPathways to Improve Educational Capabilities

This thesis represents my work at the Maastricht Science Programme, Maastricht University to create "pathway stories" for WikiPathways

Pathway information extracted from 25 years of pathway figures

Thousands of pathway diagrams are published each year as static figures inaccessible to computational queries and analyses. Using a combination of machine learning, optical character recognition, and manual curation, we identified 64,643 pathway figures published between 1995 and 2019 and extracted 1,112,551 instances of human genes, comprising 13,464 unique NCBI genes, participating in a wide variety of biological processes. This collection represents an order of magnitude more genes than found in the text of the same papers, and thousands of genes missing from other pathway databases, thus presenting new opportunities for discovery and research

Pathway information extracted from 25 years of pathway figures

Thousands of pathway diagrams are published each year as static figures inaccessible to computational queries and analyses. Using a combination of machine learning, optical character recognition, and manual curation, we identified 64,643 pathway figures published between 1995 and 2019 and extracted 1,112,551 instances of human genes, comprising 13,464 unique NCBI genes, participating in a wide variety of biological processes. This collection represents an order of magnitude more genes than found in the text of the same papers, and thousands of genes missing from other pathway databases, thus presenting new opportunities for discovery and research

Using the Semantic Web for Rapid Integration of WikiPathways with Other Biological Online Data Resources

The diversity of online resources storing biological data in different formats provides a challenge for bioinformaticians to integrate and analyse their biological data. The semantic web provides a standard to facilitate knowledge integration using statements built as triples describing a relation between two objects. WikiPathways, an online collaborative pathway resource, is now available in the semantic web through a SPARQL endpoint at http://sparql.wikipathways.org. Having biological pathways in the semantic web allows rapid integration with data from other resources that contain information about elements present in pathways using SPARQL queries. In order to convert WikiPathways content into meaningful triples we developed two new vocabularies that capture the graphical representation and the pathway logic, respectively. Each gene, protein, and metabolite in a given pathway is defined with a standard set of identifiers to support linking to several other biological resources in the semantic web. WikiPathways triples were loaded into the Open PHACTS discovery platform and are available through its Web API (https://dev.openphacts.org/docs) to be used in various tools for drug development. We combined various semantic web resources with the newly converted WikiPathways content using a variety of SPARQL query types and third-party resources, such as the Open PHACTS API. The ability to use pathway information to form new links across diverse biological data highlights the utility of integrating WikiPathways in the semantic web

Using the Semantic Web for Rapid Integration of WikiPathways with Other Biological Online Data Resources

The diversity of online resources storing biological data in different formats provides a challenge for bioinformaticians to integrate and analyse their biological data. The semantic web provides a standard to facilitate knowledge integration using statements built as triples describing a relation between two objects. WikiPathways, an online collaborative pathway resource, is now available in the semantic web through a SPARQL endpoint at http://sparql.wikipathways.org. Having biological pathways in the semantic web allows rapid integration with data from other resources that contain information about elements present in pathways using SPARQL queries. In order to convert WikiPathways content into meaningful triples we developed two new vocabularies that capture the graphical representation and the pathway logic, respectively. Each gene, protein, and metabolite in a given pathway is defined with a standard set of identifiers to support linking to several other biological resources in the semantic web. WikiPathways triples were loaded into the Open PHACTS discovery platform and are available through its Web API (https://dev.openphacts.org/docs) to be used in various tools for drug development. We combined various semantic web resources with the newly converted WikiPathways content using a variety of SPARQL query types and third-party resources, such as the Open PHACTS API. The ability to use pathway information to form new links across diverse biological data highlights the utility of integrating WikiPathways in the semantic web

Curation, Visualization and Analysis of Biological Pathways

<p>Pathway diagrams are found everywhere: in textbooks, in review articles, on posters and on whiteboards. Their utility to biologists as conceptual models is obvious. They have also become immensely useful for computational analysis and interpretationof large-scale experimental data when properly modeled. We will highlight the latest developments and newest features of WikiPathways (www.wikipathways.org), a community curated pathway database that enables researchers to capture rich, intuitive models of pathways. WikiPathways and the associated tools PathVisio and pathvisio.js are developed as open source projects with a lot of community engagement.</p> <p>The new interactive JavaScript-based pathway viewer, pathvisio.js (https://github.com/wikipathways/pathvisiojs/), is integrated in the WikiPathways website and enables users to zoom in and click on pathway elements to show linkouts to other databases. In the future pathvisio.js will replace the Java applet editor and introduce a quick and simple way to curate and edit pathways.</p> <p>The standalone pathway editor and analysis and visualization tool, PathVisio (www.pathvisio.org), was refactored with the goal to achieve a better, modular system that can be easily extended with plugins. Plugins are accessible through the new plugin repository and can be installed through the plugin manager from within the application. This is an important aspect of usability that will allow users to build an application with all the necessary modules relevant for their work. The WikiPathways plugin of PathVisio allows searching and browsing WikiPathways from within PathVisio. Furthermore users can upload new pathways or update existing pathways.</p

Example queries handled by the WikiPathways SPARQL endpoint.

<p>Example queries handled by the WikiPathways SPARQL endpoint.</p

Example federated queries handled by the WikiPathways SPARQL endpoint.

<p>Example federated queries handled by the WikiPathways SPARQL endpoint.</p