José Luis Ambite

Bio: José Luis Ambite is an academic researcher from University of Southern California. The author has contributed to research in topics: Population & Genome-wide association study. The author has an hindex of 38, co-authored 152 publications receiving 5020 citations. Previous affiliations of José Luis Ambite include Information Sciences Institute & Georgia State University.

Genetic analyses of diverse populations improves discovery for complex traits

Abstract: Genome-wide association studies (GWAS) have laid the foundation for investigations into the biology of complex traits, drug development and clinical guidelines. However, the majority of discovery efforts are based on data from populations of European ancestry1-3. In light of the differential genetic architecture that is known to exist between populations, bias in representation can exacerbate existing disease and healthcare disparities. Critical variants may be missed if they have a low frequency or are completely absent in European populations, especially as the field shifts its attention towards rare variants, which are more likely to be population-specific4-10. Additionally, effect sizes and their derived risk prediction scores derived in one population may not accurately extrapolate to other populations11,12. Here we demonstrate the value of diverse, multi-ethnic participants in large-scale genomic studies. The Population Architecture using Genomics and Epidemiology (PAGE) study conducted a GWAS of 26 clinical and behavioural phenotypes in 49,839 non-European individuals. Using strategies tailored for analysis of multi-ethnic and admixed populations, we describe a framework for analysing diverse populations, identify 27 novel loci and 38 secondary signals at known loci, as well as replicate 1,444 GWAS catalogue associations across these traits. Our data show evidence of effect-size heterogeneity across ancestries for published GWAS associations, substantial benefits for fine-mapping using diverse cohorts and insights into clinical implications. In the United States-where minority populations have a disproportionately higher burden of chronic conditions13-the lack of representation of diverse populations in genetic research will result in inequitable access to precision medicine for those with the highest burden of disease. We strongly advocate for continued, large genome-wide efforts in diverse populations to maximize genetic discovery and reduce health disparities.

Modeling Web sources for information integration

Abstract: The Web is based on a browsing paradigm that makes it difficult to retrieve and integrate data from multiple sites. Today, the only way to do this is to build specialized applications, which are time-consuming to develop and difficult to maintain. We are addressing this problem by creating the technology and tools for rapidly constructing information agents that extract, query, and integrate data from web sources. Our approach is based on a simple, uniform representation that makes it efficient to integrate multiple sources. Instead of building specialized algorithms for handling web sources, we have developed methods for mapping web sources into this uniform representation. This approach builds on work from knowledge representation, machine learning and automated planning. The resulting system, called Ariadne, makes it fast and cheap to build new information agents that access existing web sources. Ariadne also makes it easy to maintain these agents and incorporate new sources as they become available.

The Ariadne approach to Web- based information integration

Abstract: The Web is based on a browsing paradigm that makes it difficult to retrieve and integrate data from multiple sites. Today, the only way to do this is to build specialized applications, which are time-consuming to develop and difficult to maintain. We have addressed this problem by creating the technology and tools for rapidly constructing information agents that extract, query, and integrate data from web sources. Our approach is based on a uniform representation that makes it simple and efficient to integrate multiple sources. Instead of building specialized algorithms for handling web sources, we have developed methods for mapping web sources into this uniform representation. This approach builds on work from knowledge representation, databases, machine learning and automated planning. The resulting system, called Ariadne, makes it fast and easy to build new information agents that access existing web sources. Ariadne also makes it easy to maintain these agents and incorporate new sources as they become available.

Semi-automatically mapping structured sources into the semantic web

Abstract: Linked data continues to grow at a rapid rate, but a limitation of a lot of the data that is being published is the lack of a semantic description. There are tools, such as D2R, that allow a user to quickly convert a database into RDF, but these tools do not provide a way to easily map the data into an existing ontology. This paper presents a semi-automatic approach to map structured sources to ontologies in order to build semantic descriptions (source models). Since the precise mapping is sometimes ambiguous, we also provide a graphical user interface that allows a user to interactively refine the models. The resulting source models can then be used to convert data into RDF with respect to a given ontology or to define a SPARQL end point that can be queried with respect to an ontology. We evaluated the overall approach on a variety of sources and show that it can be used to quickly build source models with minimal user interaction.

Integration of heterogeneous knowledge sources in the CALO query manager

Abstract: We report on our effort to build a real system for integrating heterogeneous knowledge sources with different query answering and reasoning capabilities. We are conducting this work in the context of CALO (Cognitive Assistant that Learns and Organizes), a multidisciplinary project funded by DARPA to create cognitive software systems.

Integrative analysis of 111 reference human epigenomes

Abstract: The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.

Discovery and refinement of loci associated with lipid levels

Abstract: Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 × 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.

Ontology Matching

Abstract: Ontologies tend to be found everywhere. They are viewed as the silver bullet for many applications, such as database integration, peer-to-peer systems, e-commerce, semantic web services, or social networks. However, in open or evolving systems, such as the semantic web, different parties would, in general, adopt different ontologies. Thus, merely using ontologies, like using XML, does not reduce heterogeneity: it just raises heterogeneity problems to a higher level. Euzenat and Shvaikos book is devoted to ontology matching as a solution to the semantic heterogeneity problem faced by computer systems. Ontology matching aims at finding correspondences between semantically related entities of different ontologies. These correspondences may stand for equivalence as well as other relations, such as consequence, subsumption, or disjointness, between ontology entities. Many different matching solutions have been proposed so far from various viewpoints, e.g., databases, information systems, and artificial intelligence. The second edition of Ontology Matching has been thoroughly revised and updated to reflect the most recent advances in this quickly developing area, which resulted in more than 150 pages of new content. In particular, the book includes a new chapter dedicated to the methodology for performing ontology matching. It also covers emerging topics, such as data interlinking, ontology partitioning and pruning, context-based matching, matcher tuning, alignment debugging, and user involvement in matching, to mention a few. More than 100 state-of-the-art matching systems and frameworks were reviewed. With Ontology Matching, researchers and practitioners will find a reference book that presents currently available work in a uniform framework. In particular, the work and the techniques presented in this book can be equally applied to database schema matching, catalog integration, XML schema matching and other related problems. The objectives of the book include presenting (i) the state of the art and (ii) the latest research results in ontology matching by providing a systematic and detailed account of matching techniques and matching systems from theoretical, practical and application perspectives.

Data fusion

Abstract: The development of the Internet in recent years has made it possible and useful to access many different information systems anywhere in the world to obtain information. While there is much research on the integration of heterogeneous information systems, most commercial systems stop short of the actual integration of available data. Data fusion is the process of fusing multiple records representing the same real-world object into a single, consistent, and clean representation.This article places data fusion into the greater context of data integration, precisely defines the goals of data fusion, namely, complete, concise, and consistent data, and highlights the challenges of data fusion, namely, uncertain and conflicting data values. We give an overview and classification of different ways of fusing data and present several techniques based on standard and advanced operators of the relational algebra and SQL. Finally, the article features a comprehensive survey of data integration systems from academia and industry, showing if and how data fusion is performed in each.