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The analysis of omic data depends on machine-readable information about protein interactions, modifications, and activities as found in protein interaction networks, databases of post-translational modifications, and curated models of gene and protein function. These resources typically depend heavily on human curation. Natural language processing systems that read the primary literature have the potential to substantially extend knowledge resources while reducing the burden on human curators. However, machine-reading systems are limited by high error rates and commonly generate fragmentary and redundant information. Here, we describe an approach to precisely assemble molecular mechanisms at scale using multiple natural language processing systems and the Integrated Network and Dynamical Reasoning Assembler (INDRA). INDRA identifies full and partial overlaps in information extracted from published papers and pathway databases, uses predictive models to improve the reliability of machine reading, and thereby assembles individual pieces of information into non-redundant and broadly usable mechanistic knowledge. Using INDRA to create high-quality corpora of causal knowledge we show it is possible to extend protein-protein interaction databases and explain co-dependencies in the Cancer Dependency Map., (© 2023 The Authors. Published under the terms of the CC BY 4.0 license.)

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., (© 2021 The Authors. Published under the terms of the CC BY 4.0 license.)

Word models (natural language descriptions of molecular mechanisms) are a common currency in spoken and written communication in biomedicine but are of limited use in predicting the behavior of complex biological networks. We present an approach to building computational models directly from natural language using automated assembly. Molecular mechanisms described in simple English are read by natural language processing algorithms, converted into an intermediate representation, and assembled into executable or network models. We have implemented this approach in the Integrated Network and Dynamical Reasoning Assembler (INDRA), which draws on existing natural language processing systems as well as pathway information in Pathway Commons and other online resources. We demonstrate the use of INDRA and natural language to model three biological processes of increasing scope: (i) p53 dynamics in response to DNA damage, (ii) adaptive drug resistance in BRAF-V600E-mutant melanomas, and (iii) the RAS signaling pathway. The use of natural language makes the task of developing a model more efficient and it increases model transparency, thereby promoting collaboration with the broader biology community., (© 2017 The Authors. Published under the terms of the CC BY 4.0 license.)