3PD: Rapid design of optimal primers for chromosome conformation capture assays

<p>Abstract</p> <p>Background</p> <p>Higher eukaryotes control the expression of their genes by mechanisms that we are just beginning to understand. A complex layer of control is the dynamic spatial organization of the nucleus.</p> <p>Results</p> <p>We present a bioinformatics solution (3PD) to support the experimentalist in detecting long-ranging <it>intra </it>or <it>inter </it>chromosomal contacts by Chromosome conformation capture (3C) assays. 3C assays take a snapshot of chromosomal contacts by a fixation step and quantify them by PCR. Our contribution is to rapidly design an optimal primer set for the crucial PCR step. Our primer design reduces the level of experimental error as primers are highly similar in terms of physical properties and amplicon length. All 3C primers are compatible with multiplex PCR reactions. Primer uniqueness is checked genome-wide with a suitable index structure.</p> <p>Conclusions</p> <p>In summary, our software 3PD facilitates genome-wide primer design for 3C experiments in a matter of seconds. Our software is available as a web server at: <url>http://www.pristionchus.org/3CPrimerDesign/</url>.</p

Preliminary Aircraft Design within a Multidisciplinary and Multifidelity Design Environment

In this paper, the preliminary aircraft design tool openAD is presented. Over the past years the DLR has developed a multidisciplinary and multifidelity design environment for aircraft design to evaluate and assess various concepts and technologies at aircraft level. Thereby, a valid and consistent design can be derived by a minimum set of top-level aircraft requirements. This design environment is highly modular where the domain specific tools are provided and hosted across the different DLR institutes. As part of the design process, openAD was developed as the key enabler for overall aircraft design and assessment

Integrative analysis revealed the molecular mechanism underlying RBM10-mediated splicing regulation: RBM10 mediated alternative splicing

RBM10 encodes an RNA binding protein. Mutations in RBM10 are known to cause multiple congenital anomaly syndrome in male humans, the TARP syndrome. However, the molecular function of RBM10 is unknown. Here we used PAR-CLIP to identify thousands of binding sites of RBM10 and observed significant RBM10–RNA interactions in the vicinity of splice sites. Computational analyses of binding sites as well as loss-of-function and gain-of-function experiments provided evidence for the function of RBM10 in regulating exon skipping and suggested an underlying mechanistic model, which could be subsequently validated by minigene experiments. Furthermore, we demonstrated the splicing defects in a patient carrying an RBM10 mutation, which could be explained by disrupted function of RBM10 in splicing regulation. Overall, our study established RBM10 as an important regulator of alternative splicing, presented a mechanistic model for RBM10-mediated splicing regulation and provided a molecular link to understanding a human congenital disorder

Epigenetic dynamics of monocyte-to-macrophage differentiation

Background Monocyte-to-macrophage differentiation involves major biochemical and structural changes. In order to elucidate the role of gene regulatory changes during this process, we used high-throughput sequencing to analyze the complete transcriptome and epigenome of human monocytes that were differentiated in vitro by addition of colony-stimulating factor 1 in serum-free medium. Results Numerous mRNAs and miRNAs were significantly up- or down-regulated. More than 100 discrete DNA regions, most often far away from transcription start sites, were rapidly demethylated by the ten eleven translocation enzymes, became nucleosome-free and gained histone marks indicative of active enhancers. These regions were unique for macrophages and associated with genes involved in the regulation of the actin cytoskeleton, phagocytosis and innate immune response. Conclusions In summary, we have discovered a phagocytic gene network that is repressed by DNA methylation in monocytes and rapidly de-repressed after the onset of macrophage differentiation

Inductive logic programming for gene regulation prediction

We present a systems biology application of ILP, where the goal is to predict the regulation of a gene under a certain condition from binding site information, the state of regulators, and additional information. In the experiments, the boosted Tilde model is on par with the original model by Middendorf et al. based on alternating decision trees (ADTrees), given the same information. Adding functional categorizations and protein-protein interactions, however, it is possible to improve the performance substantially. We believe that decoding the regulation mechanisms of genes is an exciting new application of learning in logic, requiring data integration from various sources and potentially contributing to a better understanding on a system level

Inductive logic programming for gene regulation prediction

We present a systems biology application of ILP, where the goal is to predict the regulation of a gene under a certain condition from binding site information, the state of regulators, and additional information. In the experiments, the boosted Tilde model is on par with the original model by Middendorf et al. based on alternating decision trees (ADTrees), given the same information. Adding functional categorizations and protein-protein interactions, however, it is possible to improve the performance substantially. We believe that decoding the regulation mechanisms of genes is an exciting new application of learning in logic, requiring data integration from various sources and potentially contributing to a better understanding on a system level

Logic-based information integration and machine learning for gene regulation prediction

One of the central goals in computational and systems biology is to understand the mechanisms of gene transcriptional regulation on a system-wide level. The efforts are often based on high-throughput genomic data of model organism