118 research outputs found

    Privacy Preserving ID3 over Horizontally, Vertically and Grid Partitioned Data

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    We consider privacy preserving decision tree induction via ID3 in the case where the training data is horizontally or vertically distributed. Furthermore, we consider the same problem in the case where the data is both horizontally and vertically distributed, a situation we refer to as grid partitioned data. We give an algorithm for privacy preserving ID3 over horizontally partitioned data involving more than two parties. For grid partitioned data, we discuss two different evaluation methods for preserving privacy ID3, namely, first merging horizontally and developing vertically or first merging vertically and next developing horizontally. Next to introducing privacy preserving data mining over grid-partitioned data, the main contribution of this paper is that we show, by means of a complexity analysis that the former evaluation method is the more efficient.Comment: 25 page

    ModuleDigger: an itemset mining framework for the detection of cis-regulatory modules

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    Background: The detection of cis-regulatory modules (CRMs) that mediate transcriptional responses in eukaryotes remains a key challenge in the postgenomic era. A CRM is characterized by a set of co-occurring transcription factor binding sites (TFBS). In silico methods have been developed to search for CRMs by determining the combination of TFBS that are statistically overrepresented in a certain geneset. Most of these methods solve this combinatorial problem by relying on computational intensive optimization methods. As a result their usage is limited to finding CRMs in small datasets (containing a few genes only) and using binding sites for a restricted number of transcription factors (TFs) out of which the optimal module will be selected. Results: We present an itemset mining based strategy for computationally detecting cis-regulatory modules (CRMs) in a set of genes. We tested our method by applying it on a large benchmark data set, derived from a ChIP-Chip analysis and compared its performance with other well known cis-regulatory module detection tools. Conclusion: We show that by exploiting the computational efficiency of an itemset mining approach and combining it with a well-designed statistical scoring scheme, we were able to prioritize the biologically valid CRMs in a large set of coregulated genes using binding sites for a large number of potential TFs as input

    Inferring transcriptional modules from ChIP-chip, motif and microarray data

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    'ReMoDiscovery' is an intuitive algorithm to correlate regulatory programs with regulators and corresponding motifs to a set of co-expressed genes. It exploits in a concurrent way three independent data sources: ChIP-chip data, motif information and gene expression profiles. When compared to published module discovery algorithms, ReMoDiscovery is fast and easily tunable. We evaluated our method on yeast data, where it was shown to generate biologically meaningful findings and allowed the prediction of potential novel roles of transcriptional regulators

    Identification and characterization of nanobodies targeting the EphA4 receptor

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    The ephrin receptor A4 (EphA4) is one of the receptors in the ephrin system that plays a pivotal role in a variety of cell-cell interactions, mostly studied during development. In addition, EphA4 has been found to play a role in cancer biology as well as in the pathogenesis of several neurological disorders such as stroke, spinal cord injury, multiple sclerosis, amyotrophic lateral sclerosis (ALS), and Alzheimer's disease. Pharmacological blocking of EphA4 has been suggested to be a therapeutic strategy for these disorders. Therefore, the aim of our study was to generate potent and selective Nanobodies against the ligand-binding domain of the human EphA4 receptor. Weidentified two Nanobodies, Nb 39 and Nb 53, that bind EphA4 with affinities in the nanomolar range. These Nanobodies were most selective for EphA4, with residual binding to EphA7 only. Using Alphascreen technology, we found that both Nanobodies displaced all known EphA4-binding ephrins from the receptor. Furthermore, Nb39 andNb53 inhibited ephrin-induced phosphorylationoftheEphA4proteininacell-basedassay. Finally, in a cortical neuron primary culture, both Nanobodies were able to inhibit endogenous EphA4-mediated growth-cone collapse induced by ephrin-B3. Our results demonstrate the potential of Nanobodies to target the ligand-binding domain of EphA4. These Nanobodiesmaydeservefurtherevaluationaspotentialtherapeutics in disorders in which EphA4-mediated signaling plays a role

    Intraosseous Schwannoma (Neurilemmoma) of the Cervical Spine

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    Purpose: To report on an extremely rare tumour located in the cervical spine, its treatment and result. Review of the literature

    In silico identification and experimental validation of PmrAB targets in Salmonella typhimurium by regulatory motif detection

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    BACKGROUND: The PmrAB (BasSR) two-component regulatory system is required for Salmonella typhimurium virulence. PmrAB-controlled modifications of the lipopolysaccharide (LPS) layer confer resistance to cationic antibiotic polypeptides, which may allow bacteria to survive within macrophages. The PmrAB system also confers resistance to Fe(3+)-mediated killing. New targets of the system have recently been discovered that seem not to have a role in the well-described functions of PmrAB, suggesting that the PmrAB-dependent regulon might contain additional, unidentified targets. RESULTS: We performed an in silico analysis of possible targets of the PmrAB system. Using a motif model of the PmrA binding site in DNA, genome-wide screening was carried out to detect PmrAB target genes. To increase confidence in the predictions, all putative targets were subjected to a cross-species comparison (phylogenetic footprinting) using a Gibbs sampling-based motif-detection procedure. As well as the known targets, we detected additional targets with unknown functions. Four of these were experimentally validated (yibD, aroQ, mig-13 and sseJ). Site-directed mutagenesis of the PmrA-binding site (PmrA box) in yibD revealed specific sequence requirements. CONCLUSIONS: We demonstrated the efficiency of our procedure by recovering most of the known PmrAB-dependent targets and by identifying unknown targets that we were able to validate experimentally. We also pinpointed directions for further research that could help elucidate the S. typhimurium virulence pathway

    Assessment of the Microbiota in Microdissected Tissues of Crohn's Disease Patients

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    The microbiota of the gastrointestinal tract is frequently mentioned as one of the key players in the etiopathogenesis of Crohn's disease (CD). Four hypotheses have been suggested: the single, still unknown bacterial pathogen, an abnormal overall composition of the bowel microbiota (“dysbiosis”), an abnormal immunological reaction to an essentially normally composed microbiota, and increased bacterial translocation. We propose that laser capture microdissection of selected microscopic structures, followed by broad-range 16S rRNA gene sequencing, is an excellent method to assess spatiotemporal alterations in the composition of the bowel microbiota in CD. Using this approach, we demonstrated significant changes of the composition, abundance, and location of the gut microbiome in this disease. Some of these abnormal findings persisted even after macroscopic mucosal healing. Further investigations along these lines may lead to a better understanding of the possible involvement of the bowel bacteria in the development of clinical Crohn's disease

    DISTILLER: a data integration framework to reveal condition dependency of complex regulons in Escherichia coli

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    DISTILLER, a data integration framework for the inference of transcriptional module networks, is presented and used to investigate the condition dependency and modularity in Escherichia coli networks
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