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

Access to recorded interviews: A research agenda

Recorded interviews form a rich basis for scholarly inquiry. Examples include oral histories, community memory projects, and interviews conducted for broadcast media. Emerging technologies offer the potential to radically transform the way in which recorded interviews are made accessible, but this vision will demand substantial investments from a broad range of research communities. This article reviews the present state of practice for making recorded interviews available and the state-of-the-art for key component technologies. A large number of important research issues are identified, and from that set of issues, a coherent research agenda is proposed

Building high-quality merged ontologies from multiple sources with requirements customization

Ontologies are the prime way of organizing data in the Semantic Web. Often, it is necessary to combine several, independently developed ontologies to obtain a knowledge graph fully representing a domain of interest. Existing approaches scale rather poorly to the merging of multiple ontologies due to using a binary merge strategy. Thus, we aim to investigate the extent to which the n-ary strategy can solve the scalability problem. This thesis contributes to the following important aspects: 1. Our n-ary merge strategy takes as input a set of source ontologies and their mappings and generates a merged ontology. For efficient processing, rather than successively merging complete ontologies pairwise, we group related concepts across ontologies into partitions and merge first within and then across those partitions. 2. We take a step towards parameterizable merge methods. We have identified a set of Generic Merge Requirements (GMRs) that merged ontologies might be expected to meet. We have investigated and developed compatibilities of the GMRs by a graph-based method. 3. When multiple ontologies are merged, inconsistencies can occur due to different world views encoded in the source ontologies To this end, we propose a novel Subjective Logic-based method to handling the inconsistency occurring while merging ontologies. We apply this logic to rank and estimate the trustworthiness of conflicting axioms that cause inconsistencies within a merged ontology. 4. To assess the quality of the merged ontologies systematically, we provide a comprehensive set of criteria in an evaluation framework. The proposed criteria cover a variety of characteristics of each individual aspect of the merged ontology in structural, functional, and usability dimensions. 5. The final contribution of this research is the development of the CoMerger tool that implements all aforementioned aspects accessible via a unified interface

Towards valid and reusable reference alignments — ten basic quality checks for ontology alignments and their application to three different reference data sets

Identifying relationships between hitherto unrelated entities in different ontologies is the key task of ontology alignment. An alignment is either manually created by domain experts or automatically by an alignment system. In recent years, several alignment systems have been made available, each using its own set of methods for relation detection. To evaluate and compare these systems, typically a manually created alignment is used, the so-called reference alignment. Based on our experience with several of these reference alignments we derived requirements and translated them into simple quality checks to ensure the alignments’ validity and also their reusability. In this article, these quality checks are applied to a standard reference alignment in the biomedical domain, the Ontology Alignment Evaluation Initiative Anatomy track reference alignment, and two more recent data sets covering multiple domains, including but not restricted to anatomy and biology

A multi-species functional embedding integrating sequence and network structure

A key challenge to transferring knowledge between species is that different species have fundamentally different genetic architectures. Initial computational approaches to transfer knowledge across species have relied on measures of heredity such as genetic homology, but these approaches suffer from limitations. First, only a small subset of genes have homologs, limiting the amount of knowledge that can be transferred, and second, genes change or repurpose functions, complicating the transfer of knowledge. Many approaches address this problem by expanding the notion of homology by leveraging high-throughput genomic and proteomic measurements, such as through network alignment. In this work, we take a new approach to transferring knowledge across species by expanding the notion of homology through explicit measures of functional similarity between proteins in different species. Specifically, our kernel-based method, HANDL (Homology Assessment across Networks using Diffusion and Landmarks), integrates sequence and network structure to create a functional embedding in which proteins from different species are embedded in the same vector space. We show that inner products in this space and the vectors themselves capture functional similarity across species, and are useful for a variety of functional tasks. We perform the first whole-genome method for predicting phenologs, generating many that were previously identified, but also predicting new phenologs supported from the biological literature. We also demonstrate the HANDL embedding captures pairwise gene function, in that gene pairs with synthetic lethal interactions are significantly separated in HANDL space, and the direction of separation is conserved across species. Software for the HANDL algorithm is available at http://bit.ly/lrgr-handl.Published versio

Data-Driven Shape Analysis and Processing

Data-driven methods play an increasingly important role in discovering geometric, structural, and semantic relationships between 3D shapes in collections, and applying this analysis to support intelligent modeling, editing, and visualization of geometric data. In contrast to traditional approaches, a key feature of data-driven approaches is that they aggregate information from a collection of shapes to improve the analysis and processing of individual shapes. In addition, they are able to learn models that reason about properties and relationships of shapes without relying on hard-coded rules or explicitly programmed instructions. We provide an overview of the main concepts and components of these techniques, and discuss their application to shape classification, segmentation, matching, reconstruction, modeling and exploration, as well as scene analysis and synthesis, through reviewing the literature and relating the existing works with both qualitative and numerical comparisons. We conclude our report with ideas that can inspire future research in data-driven shape analysis and processing.Comment: 10 pages, 19 figure