ENQUIRE automatically reconstructs, expands, and drives enrichment analysis of gene and Mesh co-occurrence networks from context-specific biomedical literature

The accelerating growth of scientific literature overwhelms our capacity to manually distil complex phenomena like molecular networks linked to diseases. Moreover, biases in biomedical research and database annotation limit our interpretation of facts and generation of hypotheses. ENQUIRE (Expanding Networks by Querying Unexpectedly Inter-Related Entities) offers a time- and resource-efficient alternative to manual literature curation and database mining. ENQUIRE reconstructs and expands co-occurrence networks of genes and biomedical ontologies from user-selected input corpora and network-inferred PubMed queries. Its modest resource usage and the integration of text mining, automatic querying, and network-based statistics mitigating literature biases makes ENQUIRE unique in its broad-scope applications. For example, ENQUIRE can generate co-occurrence gene networks that reflect high-confidence, functional networks. When tested on case studies spanning cancer, cell differentiation, and immunity, ENQUIRE identified interlinked genes and enriched pathways unique to each topic, thereby preserving their underlying context specificity. ENQUIRE supports biomedical researchers by easing literature annotation, boosting hypothesis formulation, and facilitating the identification of molecular targets for subsequent experimentation.Author summary: In biomedicine, we are interested in deciphering the molecular mechanisms underlying a disease, which are often governed by complex networks of interactions between macromolecules, like the proteins originated from the genes in our DNA. Discovering these networks requires aggregating data from several published scientific studies. However, this task entails considerable challenges, because each study usually just focuses on one or a few genes, and because the latter influence the processes in our body differently depending on the context they act in, such as a specific cell or clinical condition. On the one hand, manual literature search may result in an incomplete interaction network due to the difficulty in annotating all the relevant findings in an increasingly growing corpus of publications; on the other hand, established databases of molecular interactions omit the context in which the interaction has been observed.