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
2031140266 2099082142 2075655036 2809442901
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 . Motivation: In molecular biology, as in many other scientific fields, the scale of analyses is ever increasing. Often, complex Monte Carlo simulation is required, sometimes within a large-scale multiple testing setting. The resulting computational costs may be prohibitively high. Results: We here present MCFDR, a simple, novel algorithm for false discovery rate (FDR) modulated sequential Monte Carlo (MC) multiple hypothesis testing. The algorithm iterates between adding MC samples across tests and calculating intermediate FDR values for the collection of tests. MC sampling is stopped either by sequential MC or based on a threshold on FDR. An essential property of the algorithm is that it limits the total number of MC samples whatever the number of true null hypotheses. We show on both real and simulated data that the proposed algorithm provides large gains in computational efficiency. Availability: MCFDR is implemented in the Genomic HyperBrowser ( http: hyperbrowser.uio.no mcfdr), a web-based system for genome analysis. All input data and results are available and can be reproduced through a Galaxy Pages document at: http: hyperbrowser.uio.no mcfdr u sandve p mcfdr. Contact: geirksa@ifi.uio.no We describe a system for extracting complex events among genes and proteins from biomedical literature, developed in context of the BioNLP'09 Shared Task on Event Extraction. For each event, its text trigger, class, and arguments are extracted. In contrast to the prevailing approaches in the domain, events can be arguments of other events, resulting in a nested structure that better captures the underlying biological statements. We divide the task into independent steps which we approach as machine learning problems. We define a wide array of features and in particular make extensive use of dependency parse graphs. A rule-based post-processing step is used to refine the output in accordance with the restrictions of the extraction task. In the shared task evaluation, the system achieved an F-score of 51.95 on the primary task, the best performance among the participants. Motivation: During the last decade, improvements in high-throughput sequencing have generated a wealth of genomic data. Functionally interpreting these sequences and finding the biological signals that are hallmarks of gene function and regulation is currently mostly done using automated genome annotation platforms, which mainly rely on integrated machine learning frameworks to identify different functional sites of interest, including splice sites. Splicing is an essential step in the gene regulation process, and the correct identification of splice sites is a major cornerstone in a genome annotation system. Results: In this paper, we present SpliceRover, a predictive deep learning approach that outperforms the state-of-the-art in splice site prediction. SpliceRover uses convolutional neural networks (CNNs), which have been shown to obtain cutting edge performance on a wide variety of prediction tasks. We adapted this approach to deal with genomic sequence inputs, and show it consistently outperforms already existing approaches, with relative improvements in prediction effectiveness of up to 80.9 when measured in terms of false discovery rate. However, a major criticism of CNNs concerns their 'black box' nature, as mechanisms to obtain insight into their reasoning processes are limited. To facilitate interpretability of the SpliceRover models, we introduce an approach to visualize the biologically relevant information learnt. We show that our visualization approach is able to recover features known to be important for splice site prediction (binding motifs around the splice site, presence of polypyrimidine tracts and branch points), as well as reveal new features (e.g. several types of exclusion patterns near splice sites).