We validate our results using data from genome-wide TF knockout experiments.

Thus, we developed a general-purpose computational method using logic-circuit models from electronics and applied it to a human leukemia dataset, identifying the genome-Wide cooperatiVity of transcription factors and microRNAs.

To our knowledge, the present study describes for the first time the use of 16 logic operations to perform a comprehensive genome-wide analysis of regulatory triplets.

The rapidly increasing amount of high throughput sequencing data offers novel and diverse resources to probe molecular functions on a genome-wide scale.

On a genome-wide scale ChIP-Seq provides regulatory information about wiring between RFs and targets, while RNA-Seq provides gene eXpression data; by combining these two data types we are able to go beyond the regulatory activities of individual RFs and investigate the relationships between higher order RF groups.

While this model is not able to capture the very complex regulatory patterns that may be characterized by continuous models [12,13], it is computationally efficient, and it is comprehensive enough to meaningfully describe a large variety of regulatory networks on a genome-wide scale in multiple organisms.

We apply Loregic to find the logic operations that characterize the FFLs from a genome-Wide perspective in both the yeast cell cycle and human leukemia cancer datasets.

We used yeast genome-wide TF knockout experiments to validate the TF logic from gate-consistent triplets.

We characterise IEGs in a genome-wide sequencing dataset that captures their transcriptional response over time.

Genome-wide analysis of enhancer activity was then performed.

Such similarities and differences between the epigenetic regulation of lncRNA and mRNA have been reported previously in genome-wide data [17].

Gene sets assigned to the best fitting model can be tested for over-representa-tion of established gene and pathway annotations, and can be integrated with genome-wide data sets to test additional hypotheses.

The transcription of primary miRNA transcripts (pri-miRNAs), and the subsequent role of the mature transcripts in the immediate-early response is unexplored in genome-wide data.

Genome-wide characterisation of histone modifications H3K4me3 and H3K27me3 at lncRNA has demonstrated common features with mRNA, whereas patterns of DNA methylation differ [17].

Using these unique datasets, and a novel approach to time series analysis, we identify a comprehensive set of transcripts whose expression patterns are altered in response to a stimulus genome-wide , including all ncRNA transcripts present.

Immediate early genes are typically shorter in length than the genome-wide average [6].

The genome-Wide CAGE data considered here necessarily included transcripts Whose functions are unknown thus we began by hypothesising the possible kinetics they may display, rather than by constructing a detailed, interconnected systems model.

The gene-disease associations were retrieved from OMIM (Online Mendelian Inheritance in Man; http://WWW.ncbi.nlm.nih.g0V/ omim) [51] and GWAS ( Genome-Wide Association Studies.

We use a genome-wide significance cutoff of p-value g 5 - 10—8.

With recent advances in genome-wide disease gene association [9] and high-throughput Interactome mapping [10] we can already pinpoint the approximate location for some disease modules (Fig.

Our in silico analysis carried out genome-wide via the StabFIex algorithm, shows the conserved presence of highly flexible regions in budding yeast genome as well as in genomes of other Saccharomyces sensu stricto species.

The extent of this correlation Will be determined by a comparable genome-Wide analysis on human sequence DNA flexibility.

A very favourable condition is the large availability of genome-wide data concerning the structural and functional aspects.