In recent years, researchers were interested in learning knowledge graph (KG) embeddings because of their advantages in downstream tasks like link prediction, entity disambiguation, and entity Classification in KGs. The state-of-the-art KG embedding models are mainly implemented in a centralized environment, i.e., they are trained on a single machine. However, most of the real-world KGs are huge in size, and a single machine is not enough to store the whole KG and train embedding models in this context. There are a few frameworks for learning KG embeddings in distributed environments. In this paper, we propose a novel distributed framework, namely DKGR, for training geometric embedding models. Our framework uses the Ray platform as a distributed environment. We evaluate our framework for the link prediction task on real-world datasets. Our preliminary results show a good speed-up when training KG embedding models in our framework. They also show that DKGR is scalable to large-scale KGs without affecting the link prediction performance remarkably.

BACKGROUND: The RNA-Recognition motif (RRM) is a protein domain that binds single-stranded RNA (ssRNA) and is present in as much as 2% of the human genome. Despite this important role in biology, RRM-ssRNA interactions are very challenging to study on the structural level because of the remarkable flexibility of ssRNA. In the absence of atomic-level experimental data, the only method able to predict the 3D structure of protein-ssRNA complexes with any degree of accuracy is ssRNA'TTRACT, an ssRNA fragment-based docking approach using ATTRACT. However, since ATTRACT parameters are not ssRNA-specific and were determined in 2010, there is substantial opportunity for enhancement. RESULTS: Here we present HIPPO, a composite RRM-ssRNA scoring potential derived analytically from contact frequencies in near-native versus non-native docking models. HIPPO consists of a consensus of four distinct potentials, each extracted from a distinct reference pool of protein-trinucleotide docking decoys. To score a docking pose with one potential, for each pair of RNA-protein coarse-grained bead types, each contact is awarded or penalised according to the relative frequencies of this contact distance range among the correct and incorrect poses of the reference pool. Validated on a fragment-based docking benchmark of 57 experimentally solved RRM-ssRNA complexes, HIPPO achieved a threefold or higher enrichment for half of the fragments, versus only a quarter with the ATTRACT scoring function. In particular, HIPPO drastically improved the chance of very high enrichment (12-fold or higher), a scenario where the incremental modelling of entire ssRNA chains from fragments becomes viable. However, for the latter result, more research is needed to make it directly practically applicable. Regardless, our approach already improves upon the state of the art in RRM-ssRNA modelling and is in principle extendable to other types of protein-nucleic acid interactions.

A current challenge in graph clustering is to tackle the issue of complex networks, i.e , graphs with attributed vertices and/or edges. In this paper, we present GraphTrees, a novel method that relies on random decision trees to compute pairwise dissimilarities between vertices in a graph. We show that using different types of trees, it is possible to extend this framework to graphs where the vertices have attributes. While many existing methods that tackle the problem of clustering vertices in an attributed graph are limited to categorical attributes, GraphTrees can handle heterogeneous types of vertex attributes. Moreover, unlike other approaches, the attributes do not need to be preprocessed. We also show that our approach is competitive with well-known methods in the case of non-attributed graphs in terms of quality of clustering, and provides promising results in the case of vertex-attributed graphs. By extending the use of an already well established approach – the random trees – to graphs, our proposed approach opens new research directions, by leveraging decades of research on this topic.

BACKGROUND: Drug side effects represent a common reason for stopping drug development during clinical trials. Improving our ability to understand drug side effects is necessary to reduce attrition rates during drug development as well as the risk of discovering novel side effects in available drugs. Today, most investigations deal with isolated side effects and overlook possible redundancy and their frequent co-occurrence. RESULTS: In this work, drug annotations are collected from SIDER and DrugBank databases. Terms describing individual side effects reported in SIDER are clustered with a semantic similarity measure into term clusters (TCs). Maximal frequent itemsets are extracted from the resulting drug x TC binary table, leading to the identification of what we call side-effect profiles (SEPs). A SEP is defined as the longest combination of TCs which are shared by a significant number of drugs. Frequent SEPs are explored on the basis of integrated drug and target descriptors using two machine learning methods: decision-trees and inductive-logic programming. Although both methods yield explicit models, inductive-logic programming method performs relational learning and is able to exploit not only drug properties but also background knowledge. Learning efficiency is evaluated by cross-validation and direct testing with new molecules. Comparison of the two machine-learning methods shows that the inductive-logic-programming method displays a greater sensitivity than decision trees and successfully exploit background knowledge such as functional annotations and pathways of drug targets, thereby producing rich and expressive rules. All models and theories are available on a dedicated web site. CONCLUSIONS: Side effect profiles covering significant number of drugs have been extracted from a drug ×side-effect association table. Integration of background knowledge concerning both chemical and biological spaces has been combined with a relational learning method for discovering rules which explicitly characterize drug-SEP associations. These rules are successfully used for predicting SEPs associated with new drugs.

MOTIVATION: In recent years, much structural information on protein domains and their pair-wise interactions has been made available in public databases. However, it is not yet clear how best to use this information to discover general rules or interaction patterns about structural protein-protein interactions. Improving our ability to detect and exploit structural interaction patterns will help to provide a better 3D picture of the known protein interactome, and will help to guide docking-based predictions of the 3D structures of unsolved protein complexes. RESULTS: This article presents KBDOCK, a 3D database approach for spatially clustering protein binding sites and for performing template-based (knowledge-based) protein docking. KBDOCK combines residue contact information from the 3DID database with the Pfam protein domain family classification together with coordinate data from the Protein Data Bank. This allows the 3D configurations of all known hetero domain-domain interactions to be superposed and clustered for each Pfam family. We find that most Pfam domain families have up to four hetero binding sites, and over 60% of all domain families have just one hetero binding site. The utility of this approach for template-based docking is demonstrated using 73 complexes from the Protein Docking Benchmark. Overall, up to 45 out of 73 complexes may be modelled by direct homology to existing domain interfaces, and key binding site information is found for 24 of the 28 remaining complexes. These results show that KBDOCK can often provide useful information for predicting the structures of unknown protein complexes. AVAILABILITY: http://kbdock.loria.fr/ CONTACT: [email protected] SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

In this paper we propose an approach which combines semantic resources and formal concept analysis to deal with heterogenous data sets represented as many-valued (MV) formal contexts. We define a new Galois connection considering the semantic relationships between attribute values in a MV context. The semantic relationships are used to calculate the similarity between attribute values to decide whether an attribute is shared by a set of objects or not. Then, based on this Galois connection, we define MV formal concepts and MV concept lattices. Depending on a chosen similarity threshold, MV concept lattices may have different levels of precision. We take advantage of this feature to browse the content of a biological databases repository in a dynamic and progressive way. The browsing process combines the navigation in several MV concept lattices and allows zooming operations by switching between MV concept lattices with higher or lower precision.

BACKGROUND: The Gene Ontology (GO) is a well known controlled vocabulary describing the biological process, molecular function and cellular component aspects of gene annotation. It has become a widely used knowledge source in bioinformatics for annotating genes and measuring their semantic similarity. These measures generally involve the GO graph structure, the information content of GO aspects, or a combination of both. However, only a few of the semantic similarity measures described so far can handle GO annotations differently according to their origin (i.e. their evidence codes). RESULTS: We present here a new semantic similarity measure called IntelliGO which integrates several complementary properties in a novel vector space model. The coefficients associated with each GO term that annotates a given gene or protein include its information content as well as a customized value for each type of GO evidence code. The generalized cosine similarity measure, used for calculating the dot product between two vectors, has been rigorously adapted to the context of the GO graph. The IntelliGO similarity measure is tested on two benchmark datasets consisting of KEGG pathways and Pfam domains grouped as clans, considering the GO biological process and molecular function terms, respectively, for a total of 683 yeast and human genes and involving more than 67,900 pair-wise comparisons. The ability of the IntelliGO similarity measure to express the biological cohesion of sets of genes compares favourably to four existing similarity measures. For inter-set comparison, it consistently discriminates between distinct sets of genes. Furthermore, the IntelliGO similarity measure allows the influence of weights assigned to evidence codes to be checked. Finally, the results obtained with a complementary reference technique give intermediate but correct correlation values with the sequence similarity, Pfam, and Enzyme classifications when compared to previously published measures. CONCLUSIONS: The IntelliGO similarity measure provides a customizable and comprehensive method for quantifying gene similarity based on GO annotations. It also displays a robust set-discriminating power which suggests it will be useful for functional clustering. AVAILABILITY: An on-line version of the IntelliGO similarity measure is available at: http://bioinfo.loria.fr/Members/benabdsi/intelligo_project/

Abstract Motivation: Computational methods are widely used to discover gene–disease relationships hidden in vast masses of available genomic and post-genomic data. In most current methods, a similarity measure is calculated between gene annotations and known disease genes or disease descriptions. However, more explicit gene–disease relationships are required for better insights into the molecular bases of diseases, especially for complex multi-gene diseases. Results: Explicit relationships between genes and diseases are formulated as candidate gene definitions that may include intermediary genes, e.g. orthologous or interacting genes. These definitions guide data modelling in our database approach for gene–disease relationship discovery and are expressed as views which ultimately lead to the retrieval of documented sets of candidate genes. A system called ACGR (Approach for Candidate Gene Retrieval) has been implemented and tested with three case studies including a rare orphan gene disease. Availability: The ACGR sources are freely available at http://bioinfo.loria.fr/projects/acgr/acgr-software/. See especially the file ‘disease_description’ and the folders ‘Xcollect_scenarios’ and ‘ACGR_views’. Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics online.

In this paper we present an extension of the Galois connection to deal with many-valued formal contexts. We define a many-valued Galois connection with respect to similarity between attribute values in a many-valued context. Then, we define many-valued formal concepts and many-valued concept lattices. Depending on a similarity threshold, many-valued concept lattices may have different levels of precision. This feature makes them very useful for multilevel conceptual clustering. Many-valued concept lattices are also used in a new lattice-based information retrieval approach for efficiently answering complex queries.

Biological databases are blooming today at an increasing rate to deal with the huge amount of data produced by genomic and post-genomic research. The need for a well-maintained searchable directory is therefore an important issue for a good exploitation of these databases. The BioRegistry repository is automatically generated from a publicly available list of biological databases (The Molecular Biology Database Collection published in Nucleic Acids Research) and aims at associating content metadata with each database in view of database retrieval and/or discovery. Such content metadata are either simple keywords or terms belonging to a medical thesaurus. Querying modalities including a search by semantic similarity are described. The use of conceptual clustering methods is proposed to build a semantic classification of biological databases enabling browsing through the BioRegistry repository and discovering previously unknown databases.

BACKGROUND: Complexity and amount of post-genomic data constitute two major factors limiting the application of Knowledge Discovery in Databases (KDD) methods in life sciences. Bio-ontologies may nowadays play key roles in knowledge discovery in life science providing semantics to data and to extracted units, by taking advantage of the progress of Semantic Web technologies concerning the understanding and availability of tools for knowledge representation, extraction, and reasoning. RESULTS: This paper presents a method that exploits bio-ontologies for guiding data selection within the preparation step of the KDD process. We propose three scenarios in which domain knowledge and ontology elements such as subsumption, properties, class descriptions, are taken into account for data selection, before the data mining step. Each of these scenarios is illustrated within a case-study relative to the search of genotype-phenotype relationships in a familial hypercholesterolemia dataset. The guiding of data selection based on domain knowledge is analysed and shows a direct influence on the volume and significance of the data mining results. CONCLUSIONS: The method proposed in this paper is an efficient alternative to numerical methods for data selection based on domain knowledge. In turn, the results of this study may be reused in ontology modelling and data integration.