Integration of molecular network data reconstructs Gene Ontology.

Motivation: Recently, a shift was made from using Gene Ontology (GO) to evaluate molecular network data to using these data to construct and evaluate GO. Dutkowski et al. provide the first evidence that a large part of GO can be reconstructed solely from topologies of molecular networks. Motivated by this work, we develop a novel data integration framework that integrates multiple types of molecular network data to reconstruct and update GO. We ask how much of GO can be recovered by integrating various molecular interaction data. Results: We introduce a computational framework for integration of various biological networks using penalized non-negative matrix tri-factorization (PNMTF). It takes all network data in a matrix form and performs simultaneous clustering of genes and GO terms, inducing new relations between genes and GO terms (annotations) and between GO terms themselves. To improve the accuracy of our predicted relations, we extend the integration methodology to include additional topological information represented as the similarity in wiring around non-interacting genes. Surprisingly, by integrating topologies of bakers’ yeasts protein–protein interaction, genetic interaction (GI) and co-expression networks, our method reports as related 96% of GO terms that are directly related in GO. The inclusion of the wiring similarity of non-interacting genes contributes 6% to this large GO term association capture. Furthermore, we use our method to infer new relationships between GO terms solely from the topologies of these networks and validate 44% of our predictions in the literature. In addition, our integration method reproduces 48% of cellular component, 41% of molecular function and 41% of biological process GO terms, outperforming the previous method in the former two domains of GO. Finally, we predict new GO annotations of yeast genes and validate our predictions through GIs profiling. Availability and implementation: Supplementary Tables of new GO term associations and predicted gene annotations are available at http://bio-nets.doc.ic.ac.uk/GO-Reconstruction/. Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics online

Hierarchical Losses and New Resources for Fine-grained Entity Typing and Linking

Extraction from raw text to a knowledge base of entities and fine-grained types is often cast as prediction into a flat set of entity and type labels, neglecting the rich hierarchies over types and entities contained in curated ontologies. Previous attempts to incorporate hierarchical structure have yielded little benefit and are restricted to shallow ontologies. This paper presents new methods using real and complex bilinear mappings for integrating hierarchical information, yielding substantial improvement over flat predictions in entity linking and fine-grained entity typing, and achieving new state-of-the-art results for end-to-end models on the benchmark FIGER dataset. We also present two new human-annotated datasets containing wide and deep hierarchies which we will release to the community to encourage further research in this direction: MedMentions, a collection of PubMed abstracts in which 246k mentions have been mapped to the massive UMLS ontology; and TypeNet, which aligns Freebase types with the WordNet hierarchy to obtain nearly 2k entity types. In experiments on all three datasets we show substantial gains from hierarchy-aware training.Comment: ACL 201