Wide-Scale Analysis of Human Functional Transcription Factor Binding Reveals a Strong Bias towards the Transcription Start Site

We introduce a novel method to screen the promoters of a set of genes with shared biological function, against a precompiled library of motifs, and find those motifs which are statistically over-represented in the gene set. The gene sets were obtained from the functional Gene Ontology (GO) classification; for each set and motif we optimized the sequence similarity score threshold, independently for every location window (measured with respect to the TSS), taking into account the location dependent nucleotide heterogeneity along the promoters of the target genes. We performed a high throughput analysis, searching the promoters (from 200bp downstream to 1000bp upstream the TSS), of more than 8000 human and 23,000 mouse genes, for 134 functional Gene Ontology classes and for 412 known DNA motifs. When combined with binding site and location conservation between human and mouse, the method identifies with high probability functional binding sites that regulate groups of biologically related genes. We found many location-sensitive functional binding events and showed that they clustered close to the TSS. Our method and findings were put to several experimental tests. By allowing a "flexible" threshold and combining our functional class and location specific search method with conservation between human and mouse, we are able to identify reliably functional TF binding sites. This is an essential step towards constructing regulatory networks and elucidating the design principles that govern transcriptional regulation of expression. The promoter region proximal to the TSS appears to be of central importance for regulation of transcription in human and mouse, just as it is in bacteria and yeast.Comment: 31 pages, including Supplementary Information and figure

FooPar: A Functional Object Oriented Parallel Framework in Scala

We present FooPar, an extension for highly efficient Parallel Computing in the multi-paradigm programming language Scala. Scala offers concise and clean syntax and integrates functional programming features. Our framework FooPar combines these features with parallel computing techniques. FooPar is designed modular and supports easy access to different communication backends for distributed memory architectures as well as high performance math libraries. In this article we use it to parallelize matrix matrix multiplication and show its scalability by a isoefficiency analysis. In addition, results based on a empirical analysis on two supercomputers are given. We achieve close-to-optimal performance wrt. theoretical peak performance. Based on this result we conclude that FooPar allows to fully access Scala's design features without suffering from performance drops when compared to implementations purely based on C and MPI

Leveraging Semantic Web Service Descriptions for Validation by Automated Functional Testing

Recent years have seen the utilisation of Semantic Web Service descriptions for automating a wide range of service-related activities, with a primary focus on service discovery, composition, execution and mediation. An important area which so far has received less attention is service validation, whereby advertised services are proven to conform to required behavioural specifications. This paper proposes a method for validation of service-oriented systems through automated functional testing. The method leverages ontology-based and rule-based descriptions of service inputs, outputs, preconditions and effects (IOPE) for constructing a stateful EFSM specification. The specification is subsequently utilised for functional testing and validation using the proven Stream X-machine (SXM) testing methodology. Complete functional test sets are generated automatically at an abstract level and are then applied to concrete Web services, using test drivers created from the Web service descriptions. The testing method comes with completeness guarantees and provides a strong method for validating the behaviour of Web services