148 research outputs found

    Predicting Combinatorial Binding of Transcription Factors to Regulatory Elements in the Human Genome by Association Rule Mining

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    Cis-acting transcriptional regulatory elements in mammalian genomes typically contain specific combinations of binding sites for various transcription factors. Although some cisregulatory elements have been well studied, the combinations of transcription factors that regulate normal expression levels for the vast majority of the 20,000 genes in the human genome are unknown. We hypothesized that it should be possible to discover transcription factor combinations that regulate gene expression in concert by identifying over-represented combinations of sequence motifs that occur together in the genome. In order to detect combinations of transcription factor binding motifs, we developed a data mining approach based on the use of association rules, which are typically used in market basket analysis. We scored each segment of the genome for the presence or absence of each of 83 transcription factor binding motifs, then used association rule mining algorithms to mine this dataset, thus identifying frequently occurring pairs of distinct motifs within a segment. Results: Support for most pairs of transcription factor binding motifs was highly correlated across different chromosomes although pair significance varied. Known true positive motif pairs showed higher association rule support, confidence, and significance than background. Our subsets of high-confidence, high-significance mined pairs of transcription factors showed enrichment for co-citation in PubMed abstracts relative to all pairs, and the predicted associations were often readily verifiable in the literature. Conclusion: Functional elements in the genome where transcription factors bind to regulate expression in a combinatorial manner are more likely to be predicted by identifying statistically and biologically significant combinations of transcription factor binding motifs than by simply scanning the genome for the occurrence of binding sites for a single transcription factor.NIAAA Alcohol Training GrantNational Science FoundationCellular and Molecular Biolog

    Constitute: The world’s constitutions to read, search, and compare

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    Constitutional design and redesign is constant. Over the last 200 years, countries have replaced their constitutions an average of every 19 years and some have amended them almost yearly. A basic problem in the drafting of these documents is the search and analysis of model text deployed in other jurisdictions. Traditionally, this process has been ad hoc and the results suboptimal. As a result, drafters generally lack systematic information about the institutional options and choices available to them. In order to address this informational need, the investigators developed a web application, Constitute [online at http://www.constituteproject.org], with the use of semantic technologies. Constitute provides searchable access to the world’s constitutions using the conceptualization, texts, and data developed by the Comparative Constitutions Project. An OWL ontology represents 330 ‘‘topics’’ – e.g. right to health – with which the investigators have tagged relevant provisions of nearly all constitutions in force as of September of 2013. The tagged texts were then converted to an RDF representation using R2RML mappings and Capsenta’s Ultrawrap. The portal implements semantic search features to allow constitutional drafters to read, search, and compare the world’s constitutions. The goal of the project is to improve the efficiency and systemization of constitutional design and, thus, to support the independence and self-reliance of constitutional drafters.Governmen

    Bounded-time fault-tolerant rule-based systems

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    Two systems concepts are introduced: bounded response-time and self-stabilization in the context of rule-based programs. These concepts are essential for the design of rule-based programs which must be highly fault tolerant and perform in a real time environment. The mechanical analysis of programs for these two properties is discussed. The techniques are used to analyze a NASA application
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