Evaluating the accuracy of a functional SNP annotation system

Many common and chronic diseases are influenced at some level by genetic variation. Research done in population genetics, specifically in the area of single nucleotide polymorphisms (SNPs) is critical to understanding human genetic variation. A key element in assessing role of a given SNP is determining if the variation is likely to result in change in function. The SNP Integration Tool (SNPit) is a comprehensive tool that integrates diverse, existing predictors of SNP functionality, providing the user with information for improved association study analysis. To evaluate the SNPit system, we developed an alternative gold standard to measure accuracy using sensitivity and specificity. The results of our evaluation demonstrated that our alternative gold standard produced encouraging results

Integration of Neuroimaging and Microarray Datasets through Mapping and Model-Theoretic Semantic Decomposition of Unstructured Phenotypes

An approach towards heterogeneous neuroscience dataset integration is proposed that uses Natural Language Processing (NLP) and a knowledge-based phenotype organizer system (PhenOS) to link ontology-anchored terms to underlying data from each database, and then maps these terms based on a computable model of disease (SNOMED CT®). The approach was implemented using sample datasets from fMRIDC, GEO, The Whole Brain Atlas and Neuronames, and allowed for complex queries such as “List all disorders with a finding site of brain region X, and then find the semantically related references in all participating databases based on the ontological model of the disease or its anatomical and morphological attributes”. Precision of the NLP-derived coding of the unstructured phenotypes in each dataset was 88% (n = 50), and precision of the semantic mapping between these terms across datasets was 98% (n = 100). To our knowledge, this is the first example of the use of both semantic decomposition of disease relationships and hierarchical information found in ontologies to integrate heterogeneous phenotypes across clinical and molecular datasets

A Framework for XML-based Integration of Data, Visualization and Analysis in a Biomedical Domain

Biomedical data are becoming increasingly complex and heterogeneous in nature. The data are stored in distributed information systems, using a variety of data models, and are processed by increasingly more complex tools that analyze and visualize them. We present in this paper our framework for integrating biomedical research data and tools into a unique Web front end. Our framework is applied to the University of Washington’s Human Brain Project. Specifically, we present solutions to four integration tasks: definition of complex mappings from relational sources to XML, distributed XQuery processing, generation of heterogeneous output formats, and the integration of heterogeneous data visualization and analysis tools

A User-centric Framework for Accessing Biological Sources and Tools

Biologists face two problems in interpreting their experiments: the integration of their data with information from multiple heterogeneous sources and data analysis with bioinformatics tools. It is difficult for scientists to choose between the numerous sources and tools without assistance. Following a thorough analysis of scientists’ needs during the querying process, we found that biologists express preferences concerning the sources to be queried and the tools to be used. Interviews also showed that the querying process itself – the strategy followed – differs between scientists. In response to these findings, we have introduced a user-centric framework allowing to specify various querying processes. Then we have developed the BioGuide system which helps the scientists to choose suitable sources and tools, find complementary information in sources, and deal with divergent data. It is generic in that it can be adapted by each user to provide answers respecting his/her preferences, and obtained following his/her strategies

Integrating and Ranking Uncertain Scientific Data

Mediator-based data integration systems resolve exploratory queries by joining data elements across sources. In the presence of uncertainties, such multiple expansions can quickly lead to spurious connections and incorrect results. The BioRank project investigates formalisms for modeling uncertainty during scientific data integration and for ranking uncertain query results. Our motivating application is protein function prediction. In this paper we show that: (i) explicit modeling of uncertainties as probabilities increases our ability to predict less-known or previously unknown functions (though it does not improve predicting the well-known). This suggests that probabilistic uncertainty models offer utility for scientific knowledge discovery; (ii) small perturbations in the input probabilities tend to produce only minor changes in the quality of our result rankings. This suggests that our methods are robust against slight variations in the way uncertainties are transformed into probabilities; and (iii) several techniques allow us to evaluate our probabilistic rankings efficiently. This suggests that probabilistic query evaluation is not as hard for real-world problems as theory indicates

XML-based approaches for the integration of heterogeneous bio-molecular data

Background: The today's public database infrastructure spans a very large collection of heterogeneous biological data, opening new opportunities for molecular biology, bio-medical and bioinformatics research, but raising also new problems for their integration and computational processing. Results: In this paper we survey the most interesting and novel approaches for the representation, integration and management of different kinds of biological data by exploiting XML and the related recommendations and approaches. Moreover, we present new and interesting cutting edge approaches for the appropriate management of heterogeneous biological data represented through XML. Conclusion: XML has succeeded in the integration of heterogeneous biomolecular information, and has established itself as the syntactic glue for biological data sources. Nevertheless, a large variety of XML-based data formats have been proposed, thus resulting in a difficult effective integration of bioinformatics data schemes. The adoption of a few semantic-rich standard formats is urgent to achieve a seamless integration of the current biological resources. </p

GenoQuery: a new querying module for functional annotation in a genomic warehouse

Motivation: We have to cope with both a deluge of new genome sequences and a huge amount of data produced by high-throughput approaches used to exploit these genomic features. Crossing and comparing such heterogeneous and disparate data will help improving functional annotation of genomes. This requires designing elaborate integration systems such as warehouses for storing and querying these data