Dividing the Ontology Alignment Task with Semantic Embeddings and Logic-based Modules

Large ontologies still pose serious challenges to state-of-the-art ontology alignment systems. In this paper we present an approach that combines a neural embedding model and logic-based modules to accurately divide an input ontology matching task into smaller and more tractable matching (sub)tasks. We have conducted a comprehensive evaluation using the datasets of the Ontology Alignment Evaluation Initiative. The results are encouraging and suggest that the proposed method is adequate in practice and can be integrated within the workflow of systems unable to cope with very large ontologies

Inferring gene ontologies from pairwise similarity data.

MotivationWhile the manually curated Gene Ontology (GO) is widely used, inferring a GO directly from -omics data is a compelling new problem. Recognizing that ontologies are a directed acyclic graph (DAG) of terms and hierarchical relations, algorithms are needed that: analyze a full matrix of gene-gene pairwise similarities from -omics data; infer true hierarchical structure in these data rather than enforcing hierarchy as a computational artifact; and respect biological pleiotropy, by which a term in the hierarchy can relate to multiple higher level terms. Methods addressing these requirements are just beginning to emerge-none has been evaluated for GO inference.MethodsWe consider two algorithms [Clique Extracted Ontology (CliXO), LocalFitness] that uniquely satisfy these requirements, compared with methods including standard clustering. CliXO is a new approach that finds maximal cliques in a network induced by progressive thresholding of a similarity matrix. We evaluate each method's ability to reconstruct the GO biological process ontology from a similarity matrix based on (a) semantic similarities for GO itself or (b) three -omics datasets for yeast.ResultsFor task (a) using semantic similarity, CliXO accurately reconstructs GO (>99% precision, recall) and outperforms other approaches (<20% precision, <20% recall). For task (b) using -omics data, CliXO outperforms other methods using two -omics datasets and achieves ∼30% precision and recall using YeastNet v3, similar to an earlier approach (Network Extracted Ontology) and better than LocalFitness or standard clustering (20-25% precision, recall).ConclusionThis study provides algorithmic foundation for building gene ontologies by capturing hierarchical and pleiotropic structure embedded in biomolecular data

Semantic Heterogeneity Issues on the Web

The Semantic Web is an extension of the traditional Web in which meaning of information is well defined, thus allowing a better interaction between people and computers. To accomplish its goals, mechanisms are required to make explicit the semantics of Web resources, to be automatically processed by software agents (this semantics being described by means of online ontologies). Nevertheless, issues arise caused by the semantic heterogeneity that naturally happens on the Web, namely redundancy and ambiguity. For tackling these issues, we present an approach to discover and represent, in a non-redundant way, the intended meaning of words in Web applications, while taking into account the (often unstructured) context in which they appear. To that end, we have developed novel ontology matching, clustering, and disambiguation techniques. Our work is intended to help bridge the gap between syntax and semantics for the Semantic Web construction

Integration and mining of malaria molecular, functional and pharmacological data: how far are we from a chemogenomic knowledge space?

The organization and mining of malaria genomic and post-genomic data is highly motivated by the necessity to predict and characterize new biological targets and new drugs. Biological targets are sought in a biological space designed from the genomic data from Plasmodium falciparum, but using also the millions of genomic data from other species. Drug candidates are sought in a chemical space containing the millions of small molecules stored in public and private chemolibraries. Data management should therefore be as reliable and versatile as possible. In this context, we examined five aspects of the organization and mining of malaria genomic and post-genomic data: 1) the comparison of protein sequences including compositionally atypical malaria sequences, 2) the high throughput reconstruction of molecular phylogenies, 3) the representation of biological processes particularly metabolic pathways, 4) the versatile methods to integrate genomic data, biological representations and functional profiling obtained from X-omic experiments after drug treatments and 5) the determination and prediction of protein structures and their molecular docking with drug candidate structures. Progresses toward a grid-enabled chemogenomic knowledge space are discussed.Comment: 43 pages, 4 figures, to appear in Malaria Journa

Fair Evaluation of Global Network Aligners

Biological network alignment identifies topologically and functionally conserved regions between networks of different species. It encompasses two algorithmic steps: node cost function (NCF), which measures similarities between nodes in different networks, and alignment strategy (AS), which uses these similarities to rapidly identify high-scoring alignments. Different methods use both different NCFs and different ASs. Thus, it is unclear whether the superiority of a method comes from its NCF, its AS, or both. We already showed on MI-GRAAL and IsoRankN that combining NCF of one method and AS of another method can lead to a new superior method. Here, we evaluate MI-GRAAL against newer GHOST to potentially further improve alignment quality. Also, we approach several important questions that have not been asked systematically thus far. First, we ask how much of the node similarity information in NCF should come from sequence data compared to topology data. Existing methods determine this more-less arbitrarily, which could affect the resulting alignment(s). Second, when topology is used in NCF, we ask how large the size of the neighborhoods of the compared nodes should be. Existing methods assume that larger neighborhood sizes are better. We find that MI-GRAAL's NCF is superior to GHOST's NCF, while the performance of the methods' ASs is data-dependent. Thus, the combination of MI-GRAAL's NCF and GHOST's AS could be a new superior method for certain data. Also, which amount of sequence information is used within NCF does not affect alignment quality, while the inclusion of topological information is crucial. Finally, larger neighborhood sizes are preferred, but often, it is the second largest size that is superior, and using this size would decrease computational complexity. Together, our results give several general recommendations for a fair evaluation of network alignment methods.Comment: 19 pages. 10 figures. Presented at the 2014 ISMB Conference, July 13-15, Boston, M

Global Network Alignment

Motivation: High-throughput methods for detecting molecular interactions have lead to a plethora of biological network data with much more yet to come, stimulating the development of techniques for biological network alignment. Analogous to sequence alignment, efficient and reliable network alignment methods will improve our understanding of biological systems. Network alignment is computationally hard. Hence, devising efficient network alignment heuristics is currently one of the foremost challenges in computational biology. 

Results: We present a superior heuristic network alignment algorithm, called Matching-based GRAph ALigner (M-GRAAL), which can process and integrate any number and type of similarity measures between network nodes (e.g., proteins), including, but not limited to, any topological network similarity measure, sequence similarity, functional similarity, and structural similarity. This is efficient in resolving ties in similarity measures and in finding a combination of similarity measures yielding the largest biologically sound alignments. When used to align protein-protein interaction (PPI) networks of various species, M-GRAAL exposes the largest known functional and contiguous regions of network similarity. Hence, we use M-GRAAL’s alignments to predict functions of un-annotated proteins in yeast, human, and bacteria _C. jejuni_ and _E. coli_. Furthermore, using M-GRAAL to compare PPI networks of different herpes viruses, we reconstruct their phylogenetic relationship and our phylogenetic tree is the same as sequenced-based one