References of "Schneider, Reinhard 50003033"
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See detailCOMPARTMENTS: unification and visualization of protein subcellular localization evidence.
Binder, Janos X. UL; Pletscher-Frankild, Sune; Tsafou, Kalliopi et al

in Database: the Journal of Biological Databases and Curation (2014), 2014

Information on protein subcellular localization is important to understand the cellular functions of proteins. Currently, such information is manually curated from the literature, obtained from high ... [more ▼]

Information on protein subcellular localization is important to understand the cellular functions of proteins. Currently, such information is manually curated from the literature, obtained from high-throughput microscopy-based screens and predicted from primary sequence. To get a comprehensive view of the localization of a protein, it is thus necessary to consult multiple databases and prediction tools. To address this, we present the COMPARTMENTS resource, which integrates all sources listed above as well as the results of automatic text mining. The resource is automatically kept up to date with source databases, and all localization evidence is mapped onto common protein identifiers and Gene Ontology terms. We further assign confidence scores to the localization evidence to facilitate comparison of different types and sources of evidence. To further improve the comparability, we assign confidence scores based on the type and source of the localization evidence. Finally, we visualize the unified localization evidence for a protein on a schematic cell to provide a simple overview. Database URL: http://compartments.jensenlab.org. [less ▲]

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See detailThe HIV Mutation Browser: A Resource for Human Immunodeficiency Virus Mutagenesis and Polymorphism Data
Davey, Norman E.; Satagopam, Venkata UL; Santiago-Mozos, Salvador et al

in PLoS Computational Biology (2014)

Huge research effort has been invested over many years to determine the phenotypes of natural or artificial mutations in HIV proteins—interpretation of mutation phenotypes is an invaluable source of new ... [more ▼]

Huge research effort has been invested over many years to determine the phenotypes of natural or artificial mutations in HIV proteins—interpretation of mutation phenotypes is an invaluable source of new knowledge. The results of this research effort are recorded in the scientific literature, but it is difficult for virologists to rapidly find it. Manually locating data on phenotypic variation within the approximately 270,000 available HIV-related research articles, or the further 1,500 articles that are published each month is a daunting task. Accordingly, the HIV research community would benefit from a resource cataloguing the available HIV mutation literature. We have applied computational text-mining techniques to parse and map mutagenesis and polymorphism information from the HIV literature, have enriched the data with ancillary information and have developed a public, web-based interface through which it can be intuitively explored: the HIV mutation browser. The current release of the HIV mutation browser describes the phenotypes of 7,608 unique mutations at 2,520 sites in the HIV proteome, resulting from the analysis of 120,899 papers. The mutation information for each protein is organised in a residue-centric manner and each residue is linked to the relevant experimental literature. The importance of HIV as a global health burden advocates extensive effort to maximise the efficiency of HIV research. The HIV mutation browser provides a valuable new resource for the research community. The HIV mutation browser is available at: http://hivmut.org. [less ▲]

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See detailAddressing Technical Replicate Variance in Omics Data Analysis
Glaab, Enrico UL; Schneider, Reinhard UL

Poster (2014)

High-throughput omics datasets often contain technical replicates, included to account for technical sources of noise in the measurement process. Although summarizing these replicate measurements by using ... [more ▼]

High-throughput omics datasets often contain technical replicates, included to account for technical sources of noise in the measurement process. Although summarizing these replicate measurements by using robust averages may help to reduce the influence of noise on downstream data analysis, the information on the variance across the replicate measurements is lost in the averaging process and therefore typically disregarded in subsequent statistical analyses. We introduce RepExplore, a web-service dedicated to exploit the information captured in the technical replicate variance to provide more reliable and informative differential expression and abundance statistics for omics datasets. The software builds on previously published statistical methods, which have been applied successfully to biomedical omics data but are difficult to use without prior experience in programming or scripting. RepExplore facilitates the analysis by providing a fully automated data processing and interactive ranking tables, whisker plot, heat map and principal component analysis visualizations to interpret omics data and derived statistics. The web-based software is freely available at http://www.repexplore.tk. [less ▲]

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See detailIntegrating Pathways of Parkinson's Disease in a Molecular Interaction Map
Fujita, Kazuhiro A.; Ostaszewski, Marek UL; Matsuoka, Yukiko et al

in Molecular Neurobiology (2014)

Parkinson's disease (PD) is a major neurodegenerative chronic disease, most likely caused by a complex interplay of genetic and environmental factors. Information on various aspects of PD pathogenesis is ... [more ▼]

Parkinson's disease (PD) is a major neurodegenerative chronic disease, most likely caused by a complex interplay of genetic and environmental factors. Information on various aspects of PD pathogenesis is rapidly increasing and needs to be efficiently organized, so that the resulting data is available for exploration and analysis. Here we introduce a computationally tractable, comprehensive molecular interaction map of PD. This map integrates pathways implicated in PD pathogenesis such as synaptic and mitochondrial dysfunction, impaired protein degradation, alpha-synuclein pathobiology and neuroinflammation. We also present bioinformatics tools for the analysis, enrichment and annotation of the map, allowing the research community to open new avenues in PD research. The PD map is accessible at http://minerva.uni.lu/pd_map . [less ▲]

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See detailThe Parkinson's Disease Map: A Framework for Integration, Curation and Exploration of Disease-related Pathways
Ostaszewski, Marek UL; Fujita, Kazuhiro; Matsuoka, Yukiko et al

Poster (2013, March 09)

Objectives: The pathogenesis of Parkinson's Disease (PD) is multi-factorial and age-related, implicating various genetic and environmental factors. It becomes increasingly important to develop new ... [more ▼]

Objectives: The pathogenesis of Parkinson's Disease (PD) is multi-factorial and age-related, implicating various genetic and environmental factors. It becomes increasingly important to develop new approaches to organize and explore the exploding knowledge of this field. Methods: The published knowledge on pathways implicated in PD, such as synaptic and mitochondrial dysfunction, alpha-synuclein pathobiology, failure of protein degradation systems and neuroinflammation has been organized and represented using CellDesigner. This repository has been linked to a framework of bioinformatics tools including text mining, database annotation, large-scale data integration and network analysis. The interface for online curation of the repository has been established using Payao tool. Results: We present the PD map, a computer-based knowledge repository, which includes molecular mechanisms of PD in a visually structured and standardized way. A bioinformatics framework that facilitates in-depth knowledge exploration, extraction and curation supports the map. We discuss the insights gained from PD map-driven text mining of a corpus of over 50 thousands full text PD-related papers, integration and visualization of gene expression in post mortem brain tissue of PD patients with the map, as well as results of network analysis. Conclusions: The knowledge repository of disease-related mechanisms provides a global insight into relationships between different pathways and allows considering a given pathology in a broad context. Enrichment with available text and bioinformatics databases as well as integration of experimental data supports better understanding of complex mechanisms of PD and formulation of novel research hypotheses. [less ▲]

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See detailIAnn: An event sharing platform for the life sciences
Jimenez, Rafael; Albar, Juan; Bhak, Jong et al

in Bioinformatics (2013)

Summary: We present iAnn, an open source community-driven platform for dissemination of life science events, such as courses, conferences and workshops. iAnn allows automatic visualisation and integration ... [more ▼]

Summary: We present iAnn, an open source community-driven platform for dissemination of life science events, such as courses, conferences and workshops. iAnn allows automatic visualisation and integration of customised event reports. A central repository lies at the core of the platform: curators add submitted events, and these are subsequently accessed via web services. Thus, once an iAnn widget is incorporated into a website, it permanently shows timely relevant information as if it were native to the remote site. At the same time, announcements submitted to the repository are automatically disseminated to all portals that query the system. To facilitate the visualization of announcements, iAnn provides powerful filtering options and views, integrated in Google Maps and Google Calendar. All iAnn widgets are freely available. [less ▲]

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See detailUnraveling genomic variation from next generation sequencing data
Pavlopoulos, Georgios A.; Oulas, Anastasis; Iacucci, Ernesto et al

in BioData Mining (2013), 6(1), 13

Elucidating the content of a DNA sequence is critical to deeper understand and decode the genetic information for any biological system. As next generation sequencing (NGS) techniques have become cheaper ... [more ▼]

Elucidating the content of a DNA sequence is critical to deeper understand and decode the genetic information for any biological system. As next generation sequencing (NGS) techniques have become cheaper and more advanced in throughput over time, great innovations and breakthrough conclusions have been generated in various biological areas. Few of these areas, which get shaped by the new technological advances, involve evolution of species, microbial mapping, population genetics, genome-wide association studies (GWAs), comparative genomics, variant analysis, gene expression, gene regulation, epigenetics and personalized medicine. While NGS techniques stand as key players in modern biological research, the analysis and the interpretation of the vast amount of data that gets produced is a not an easy or a trivial task and still remains a great challenge in the field of bioinformatics. Therefore, efficient tools to cope with information overload, tackle the high complexity and provide meaningful visualizations to make the knowledge extraction easier are essential. In this article, we briefly refer to the sequencing methodologies and the available equipment to serve these analyses and we describe the data formats of the files which get produced by them. We conclude with a thorough review of tools developed to efficiently store, analyze and visualize such data with emphasis in structural variation analysis and comparative genomics. We finally comment on their functionality, strengths and weaknesses and we discuss how future applications could further develop in this field. [less ▲]

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See detailTranscriptional mechanisms underlying sensitization of peripheral sensory neurons by Granulocyte-/Granulocyte-macrophage colony stimulating factors.
Bali, Kiran Kumar; Venkataramani, Varun; Satagopam, Venkata UL et al

in Molecular pain (2013), 9(1), 48

BACKGROUND: Cancer-associated pain is a major cause of poor quality of life in cancer patients and is frequently resistant to conventional therapy. Recent studies indicate that some hematopoietic growth ... [more ▼]

BACKGROUND: Cancer-associated pain is a major cause of poor quality of life in cancer patients and is frequently resistant to conventional therapy. Recent studies indicate that some hematopoietic growth factors, namely granulocyte macrophage colony stimulating factor (GMCSF) and granulocyte colony stimulating factor (GCSF), are abundantly released in the tumor microenvironment and play a key role in regulating tumor-nerve interactions and tumor-associated pain by activating receptors on dorsal root ganglion (DRG) neurons. Moreover, these hematopoietic factors have been highly implicated in postsurgical pain, inflammatory pain and osteoarthritic pain. However, the molecular mechanisms via which G-/GMCSF bring about nociceptive sensitization and elicit pain are not known. RESULTS: In order to elucidate G-/GMCSF mediated transcriptional changes in the sensory neurons, we performed a comprehensive, genome-wide analysis of changes in the transcriptome of DRG neurons brought about by exposure to GMCSF or GCSF. We present complete information on regulated genes and validated profiling analyses and report novel regulatory networks and interaction maps revealed by detailed bioinformatics analyses. Amongst these, we validate calpain 2, matrix metalloproteinase 9 (MMP9) and a RhoGTPase Rac1 as well as Tumor necrosis factor alpha (TNFalpha) as transcriptional targets of G-/GMCSF and demonstrate the importance of MMP9 and Rac1 in GMCSF-induced nociceptor sensitization. CONCLUSION: With integrative approach of bioinformatics, in vivo pharmacology and behavioral analyses, our results not only indicate that transcriptional control by G-/GMCSF signaling regulates a variety of established pain modulators, but also uncover a large number of novel targets, paving the way for translational analyses in the context of pain disorders. [less ▲]

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See detailSignaling in Insulin-Secreting MIN6 Pseudoislets and Monolayer Cells.
Chowdhury, Azazul; Satagopam, Venkata UL; Manukyan, Levon et al

in Journal of proteome research (2013)

Cell-cell interactions are of fundamental importance for cellular function. In islets of Langerhans, which control blood glucose levels by secreting insulin in response to the blood glucose concentration ... [more ▼]

Cell-cell interactions are of fundamental importance for cellular function. In islets of Langerhans, which control blood glucose levels by secreting insulin in response to the blood glucose concentration, the secretory response of intact islets is higher than that of insulin-producing beta-cells not arranged in the islet architecture. The objective was to define mechanisms by which cellular performance is enhanced when cells are arranged in three-dimensional space. The task was addressed by making a comprehensive analysis based on protein expression patterns generated from insulin-secreting MIN6 cells grown as islet-like clusters, so-called pseudoislets, and in monolayers. After culture, glucose-stimulated insulin secretion (GSIS) was measured from monolayers and pseudoislets. GSIS rose 6-fold in pseudoislets but only 3-fold in monolayers when the glucose concentration was increased from 2 to 20 mmol/L. Proteins from pseudoislets and monolayers were extracted and analyzed by liquid-chromatography mass spectrometry, and differentially expressed proteins were mapped onto KEGG pathways. Protein profiling identified 1576 proteins, which were common to pseudoislets and monolayers. When mapped onto KEGG pathways, 11 highly enriched pathways were identified. On the basis of differences in expression of proteins belonging to the pathways in pseudoislets and monolayers, predictions of differential pathway activation were performed. Mechanisms enhancing insulin secretory capacity of the beta-cell, when situated in the islet, include pathways regulating glucose metabolism, cell interaction, and translational regulation. [less ▲]

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See detailGenome-wide identification and functional analyses of microRNA signatures associated with cancer pain.
Bali, Kiran Kumar; Selvaraj, Deepitha; Satagopam, Venkata UL et al

in EMBO Molecular Medicine (2013), 5(11), 1740-58

Cancer pain remains a major challenge and there is an urgent demand for the development of specific mechanism-based therapies. Various diseases are associated with unique signatures of expression of ... [more ▼]

Cancer pain remains a major challenge and there is an urgent demand for the development of specific mechanism-based therapies. Various diseases are associated with unique signatures of expression of microRNAs (miRNAs), which reveal deep insights into disease pathology. Using a comprehensive approach combining genome-wide miRNA screening, molecular and in silico analyses with behavioural approaches in a clinically relevant model of metastatic bone-cancer pain in mice, we now show that tumour-induced conditions are associated with a marked dysregulation of 57 miRNAs in sensory neurons corresponding to tumour-affected areas. By establishing protocols for interference with disease-induced miRNA dysregulation in peripheral sensory neurons in vivo, we functionally validate six dysregulated miRNAs as significant modulators of tumour-associated hypersensitivity. In silico analyses revealed that their predicted targets include key pain-related genes and we identified Clcn3, a gene encoding a chloride channel, as a key miRNA target in sensory neurons, which is functionally important in tumour-induced nociceptive hypersensitivity in vivo. Our results provide new insights into endogenous gene regulatory mechanisms in cancer pain and open up attractive and viable therapeutic options. [less ▲]

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See detailPhenoTimer: Software for the Visual Mapping of Time-Resolved Phenotypic Landscapes
Secrier, Maria; Schneider, Reinhard UL

in PLoS ONE (2013), 8(8), 72361

Timing common and specific modulators of disease progression is crucial for treatment, but the understanding of the underlying complex system of interactions is limited. While attempts at elucidating this ... [more ▼]

Timing common and specific modulators of disease progression is crucial for treatment, but the understanding of the underlying complex system of interactions is limited. While attempts at elucidating this experimentally have produced enormous amounts of phenotypic data, tools that are able to visualize and analyze them are scarce and the insight obtained from the data is often unsatisfactory. Linking and visualizing processes from genes to phenotypes and back, in a temporal context, remains a challenge in systems biology. We introduce PhenoTimer, a 2D/3D visualization tool for the mapping of time-resolved phenotypic links in a genetic context. It uses a novel visualization approach for relations between morphological defects, pathways or diseases, to enable fast pattern discovery and hypothesis generation. We illustrate its capabilities of tracing dynamic motifs on cell cycle datasets that explore the phenotypic order of events upon perturbations of the system, transcriptional activity programs and their connection to disease. By using this tool we are able to fine-grain regulatory programs for individual time points of the cell cycle and better understand which patterns arise when these programs fail. We also illustrate a way to identify common mechanisms of misregulation in diseases and drug abuse. [less ▲]

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See detailOnTheFly 2.0: a tool for automatic annotation of files and biological information extraction.
Pafilis, Evangelos; Pavlopoulos, Georgios; Satagopam, Venkata UL et al

Poster (2013)

Retrieving all of the necessary information from databases about bioentities mentioned in an article is not a trivial or an easy task. Following the daily literature about a specific biological topic and ... [more ▼]

Retrieving all of the necessary information from databases about bioentities mentioned in an article is not a trivial or an easy task. Following the daily literature about a specific biological topic and collecting all the necessary information about the bioentities mentioned in the literature manually is tedious and time consuming. OnTheFly 2.0 is a web application mainly designed for non-computer experts which aims to automate data collection and knowledge extraction from biological literature in a user friendly and efficient way. OnTheFly 2.0 is able to extract bioentities from individual articles such as text, Microsoft Word, Excel and PDF files. With a simple drag-and-drop motion, the text of a document is extensively parsed for bioentities such as protein/gene names and chemical compound names. Utilizing high quality data integration platforms, OnTheFly allows the generation of informative summaries, interaction networks and at-a-glance popup windows containing knowledge related to the bioentities found in documents. OnTheFly 2.0 provides a concise application to automate the extraction of bioentities hidden in various documents and is offered as a web based application. [less ▲]

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See detailComputational infrastructures for data and knowledge management in systems biology
Georgatos, Fotis UL; Ballereau, S.; Pellet, J. et al

in Prokop, Ales; Csukás, Bela (Eds.) Systems Biology: Integrative Biology and Simulation Tools (2013)

The volume, complexity and heterogeneity of data originating from high throughput functional genomics technologies have created challenges and opportunities for Information Technology (IT) departments ... [more ▼]

The volume, complexity and heterogeneity of data originating from high throughput functional genomics technologies have created challenges and opportunities for Information Technology (IT) departments. These increased demands have also led to increasing costs for IT infrastructure such as necessary computing power and storage devices, as well as further costs for manpower effort, required for maintenance. This chapter describes some of the challenges for computational analysis infrastructure, including bottlenecks and most pressing needs that have to be addressed to effectively support the development of systems biology and its application in medicine. [less ▲]

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See detailNuclear calcium signaling in spinal neurons drives a genomic program required for persistent inflammatory pain
Simonetti, Manuela; Hagenston, Anna; Vardeh, Daniel et al

in Neuron (2013), 77(1), 43-57

Persistent pain induced by noxious stimuli is characterized by the transition from normosensitivity to hypersensitivity. Underlying mechanisms are not well understood, although gene expression is ... [more ▼]

Persistent pain induced by noxious stimuli is characterized by the transition from normosensitivity to hypersensitivity. Underlying mechanisms are not well understood, although gene expression is considered important. Here we show that persistent nociceptive-like activity triggers calcium transients in neuronal nuclei within the superficial spinal dorsal horn, and that nuclear calcium is necessary for the development of long-term inflammatory hypersensitivity. Using a nucleusspecific calcium signal perturbation strategy in vivo complemented by gene profiling, bioinformatics and functional analyses, we discovered a pain-associated, nuclear calciumregulated gene program in spinal excitatory neurons. This includes C1q, a novel modulator of synaptic spine morphogenesis, which we found to contribute to activity-dependent spine remodelling on spinal neurons in a manner functionally associated with inflammatory hypersensitivity. Thus, nuclear calcium integrates synapse-to-nucleus communication following noxious stimulation and controls a spinal genomic response that mediates the transition between acute and long-term nociceptive sensitization by modulating functional and structural plasticity. [less ▲]

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See detailFunctional Genomics, Proteomics, Metabolomics and Bioinformatics for Systems Biology
Ballereau, S.; Glaab, Enrico UL; Kolodkin, Alexey UL et al

in Prokop, Ales; Csukás, Bela (Eds.) Systems Biology: Integrative Biology and Simulation Tools (2013)

This chapter introduces systems biology, its context, aims, concepts and strategies. It then describes approaches and methods used for collection of high-dimensional structural and functional genomics ... [more ▼]

This chapter introduces systems biology, its context, aims, concepts and strategies. It then describes approaches and methods used for collection of high-dimensional structural and functional genomics data, including epigenomics, transcriptomics, proteomics, metabolomics and lipidomics, and how recent technological advances in these fields have moved the bottleneck from data production to data analysis and bioinformatics. Finally, the most advanced mathematical and computational methods used for clustering, feature selection, prediction analysis, text mining and pathway analysis in functional genomics and systems biology are reviewed and discussed in the context of use cases. [less ▲]

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See detailVisualizing time-related data in biology, a review
Secrier, Maria; Schneider, Reinhard UL

in Briefings in Bioinformatics (2013)

Time is of the essence, also in biology. Monitoring disease progression or timing developmental defects are key aspects in the process of drug discovery and therapy trial. Furthermore, before deciphering ... [more ▼]

Time is of the essence, also in biology. Monitoring disease progression or timing developmental defects are key aspects in the process of drug discovery and therapy trial. Furthermore, before deciphering the course of evolution of these complex processes, we need an understanding of the basic dynamics of biological phenomena that are often strictly time-regulated (e.g. circadian rhythms). With the advances in technologies able to measure timing effects and dynamics of regulatory aspects, visualization and analysis tools try to keep up the pace with the new challenge. Beyond the classical timeline plots, notable attempts at more involved temporal interpretation have been made in the recent years, but awareness of the available resources is still limited within the scientific community. Here we review some of the advances in biological visualization of time-driven processes and look at how they allow analyzing data now and in the future. [less ▲]

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See detailBioinformatics as a driver, not a passenger, of translational biomedical research: Perspectives from the 6th Benelux bioinformatics conference.
Azuaje, F. J.; Heymann, M.; Ternes, A. M. et al

in Journal of Clinical Bioinformatics (2012), 2(7),

The 6th Benelux Bioinformatics Conference (BBC11) held in Luxembourg on 12 and 13 December 2011 attracted around 200 participants, including internationally-renowned guest speakers and more than 100 peer ... [more ▼]

The 6th Benelux Bioinformatics Conference (BBC11) held in Luxembourg on 12 and 13 December 2011 attracted around 200 participants, including internationally-renowned guest speakers and more than 100 peer-reviewed submissions from 3 continents. Researchers from the public and private sectors convened at BBC11 to discuss advances and challenges in a wide spectrum of application areas. A key theme of the conference was the contribution of bioinformatics to enable and accelerate translational and clinical research. The BBC11 stressed the need for stronger collaborating efforts across disciplines and institutions. The demonstration of the clinical relevance of systems approaches and of next-generation sequencing-based measurement technologies are among the existing opportunities for increasing impact in translational research. Translational bioinformatics will benefit from research models that strike a balance between the importance of protecting intellectual property and the need to openly access scientific and technological advances. The full conference proceedings are freely available at http://www.bbc11.lu. [less ▲]

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