The vision of @math -DB introduces deterministic scientific hypotheses as a kind of uncertain and probabilistic data, and opens some key technical challenges for enabling data-driven hypothesis management and analytics. The @math -DB system addresses those challenges throughout a design-by-synthesis pipeline that defines its architecture. It processes hypotheses from their XML-based extraction to encoding as uncertain and probabilistic U-relational data, and eventually to their conditioning in the presence of observations. In this demo we present a first prototype of the @math -DB system. We showcase its core innovative features by means of use case scenarios in computational science in which the hypotheses are extracted from a model repository on the web and evaluated (rated ranked) as probabilistic data.
. Finally, our framework is comparable with Bioinformatics' initiatives that address hypothesis encoding into the RDF data model @cite_18 . We point out the Robot Scientist, HyBrow and SWAN (cf. @cite_18 ), all of which consist in some ad-hoc RDF encoding of sequence and genome analysis hypotheses under varying levels of structure (viz., from gene G has function A' statements to free text). Our framework in turn consists in the U-relational encoding of hypotheses from mathematical equations, which is (to our knowledge) the first work on hypothesis relational encoding.
@cite_18
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A major challenge in molecular biology is reverse-engineering the cis-regulatory logic that plays a major role in the control of gene expression. This program includes searching through DNA sequences to identify “motifs” that serve as the binding sites for transcription factors or, more generally, are predictive of gene expression across cellular conditions. Several approaches have been proposed for de novo motif discovery–searching sequences without prior knowledge of binding sites or nucleotide patterns. However, unbiased validation is not straightforward. We consider two approaches to unbiased validation of discovered motifs: testing the statistical significance of a motif using a DNA “background” sequence model to represent the null hypothesis and measuring performance in predicting membership in gene clusters. We demonstrate that the background models typically used are “too null,” resulting in overly optimistic assessments of significance, and argue that performance in predicting TF binding or expression patterns from DNA motifs should be assessed by held-out data, as in predictive learning. Applying this criterion to common motif discovery methods resulted in universally poor performance, although there is a marked improvement when motifs are statistically significant against real background sequences. Moreover, on synthetic data where “ground truth” is known, discriminative performance of all algorithms is far below the theoretical upper bound, with pronounced “over-fitting” in training. A key conclusion from this work is that the failure of de novo discovery approaches to accurately identify motifs is basically due to statistical intractability resulting from the fixed size of co-regulated gene clusters, and thus such failures do not necessarily provide evidence that unfound motifs are not active biologically. Consequently, the use of prior knowledge to enhance motif discovery is not just advantageous but necessary. An implementation of the LR and ALR algorithms is available at http: code.google.com p likelihood-ratio-motifs .