53 research outputs found
Beyond Pathway Analysis: Identification of Active Subnetworks in Rett Syndrome
Pathway and network approaches are valuable tools in analysis and interpretation of large complex omics data. Even in the field of rare diseases, like Rett syndrome, omics data are available, and the maximum use of such data requires sophisticated tools for comprehensive analysis and visualization of the results. Pathway analysis with differential gene expression data has proven to be extremely successful in identifying affected processes in disease conditions. In this type of analysis, pathways from different databases like WikiPathways and Reactome are used as separate, independent entities. Here, we show for the first time how these pathway models can be used and integrated into one large network using the WikiPathways RDF containing all human WikiPathways and Reactome pathways, to perform network analysis on transcriptomics data. This network was imported into the network analysis tool Cytoscape to perform active submodule analysis. Using a publicly available Rett syndrome gene expression dataset from frontal and temporal cortex, classical enrichment analysis, including pathway and Gene Ontology analysis, revealed mainly immune response, neuron specific and extracellular matrix processes. Our active module analysis provided a valuable extension of the analysis prominently showing the regulatory mechanism of MECP2, especially on DNA maintenance, cell cycle, transcription, and translation. In conclusion, using pathway models for classical enrichment and more advanced network analysis enables a more comprehensive analysis of gene expression data and provides novel results
Advancing food, nutrition, and health research in Europe by connecting and building research infrastructures in a DISH-RI: Results of the EuroDISH project
Background: Research infrastructures (RIs) are essential to advance research on the relationship between food, nutrition, and health. RIs will facilitate innovation and allow insights at the systems level which are required to design (public health) strategies that will address societal challenges more effectively. Approach: In the EuroDISH project we mapped existing RIs in the food and health area in Europe, identified outstanding needs, and synthesised this into a conceptual design of a pan-European DISH-RI. The DISH model was used to describe and structure the research area: Determinants of food choice, Intake of foods and nutrients, Status and functional markers of nutritional health, and Health and disease risk. Key findings: The need to develop RIs in the food and health domain clearly emerged from the EuroDISH project. It showed the necessity for a unique interdisciplinary and multi-stakeholder RI that overarches the research domains. A DISH-RI should bring services to the research community that facilitate network and community building and provide access to standardised, interoperable, and innovative data and tools. It should fulfil the scientific needs to connect within and between research domains and make use of current initiatives. Added value can also be created by providing services to policy makers and industry, unlocking data and enabling valorisation of research insights in practice through public-private partnerships. The governance of these services (e.g. ownership) and the centralised and distributed activities of the RI itself (e.g. flexibility, innovation) needs to be organised and aligned with the different interests of public and private partners
Quantitative analysis of ChIP-seq data uncovers dynamic and sustained H3K4me3 and H3K27me3 modulation in cancer cells under hypoxia
The Molecular Biology of Susceptibility to Post-Traumatic Stress Disorder: Highlights of Epigenetics and Epigenomics
Exposure to trauma is one of the most important and prevalent risk factors for mental and physical ill-health. Excessive or prolonged stress exposure increases the risk of a wide variety of mental and physical symptoms. However, people differ strikingly in their susceptibility to develop signs and symptoms of mental illness after traumatic stress. Post-traumatic stress disorder (PTSD) is a debilitating disorder affecting approximately 8% of the world’s population during their lifetime, and typically develops after exposure to a traumatic event. Despite that exposure to potentially traumatizing events occurs in a large proportion of the general population, about 80–90% of trauma-exposed individuals do not develop PTSD, suggesting an inter-individual difference in vulnerability to PTSD. While the biological mechanisms underlying this differential susceptibility are unknown, epigenetic changes have been proposed to underlie the relationship between exposure to traumatic stress and the susceptibility to develop PTSD. Epigenetic mechanisms refer to environmentally sensitive modifications to DNA and RNA molecules that regulate gene transcription without altering the genetic sequence itself. In this review, we provide an overview of various molecular biological, biochemical and physiological alterations in PTSD, focusing on changes at the genomic and epigenomic level. Finally, we will discuss how current knowledge may aid us in early detection and improved management of PTSD patients
A user-friendly workflow for analysis of Illumina gene expression bead array data available at the arrayanalysis.org portal
BACKGROUND: Illumina whole-genome expression bead arrays are a widely used platform for transcriptomics. Most of the tools available for the analysis of the resulting data are not easily applicable by less experienced users. ArrayAnalysis.org provides researchers with an easy-to-use and comprehensive interface to the functionality of R and Bioconductor packages for microarray data analysis. As a modular open source project, it allows developers to contribute modules that provide support for additional types of data or extend workflows. RESULTS: To enable data analysis of Illumina bead arrays for a broad user community, we have developed a module for ArrayAnalysis.org that provides a free and user-friendly web interface for quality control and pre-processing for these arrays. This module can be used together with existing modules for statistical and pathway analysis to provide a full workflow for Illumina gene expression data analysis. The module accepts data exported from Illumina's GenomeStudio, and provides the user with quality control plots and normalized data. The outputs are directly linked to the existing statistics module of ArrayAnalysis.org, but can also be downloaded for further downstream analysis in third-party tools. CONCLUSIONS: The Illumina bead arrays analysis module is available at http://www.arrayanalysis.org . A user guide, a tutorial demonstrating the analysis of an example dataset, and R scripts are available. The module can be used as a starting point for statistical evaluation and pathway analysis provided on the website or to generate processed input data for a broad range of applications in life sciences research
Characteristics of the selected datasets.
<p>The number of excluded arrays for each dataset using the standardized QC procedure is indicated in brackets. Abbreviations: NP: normal prostate, pPC: primary prostate cancer, mPC: metastatic prostate cancer, AI: androgen independent, AD: androgen dependent.</p
Overview of the QC results of two selected datasets.
<p>Several QC results of the dataset by Varambally <i>et al.</i> comparing arrays of benign prostate tissue (maroon), primary prostate cancer (blue) and metastatic prostate cancer samples (green) are shown in panel a-d. Several QC results of the dataset by Gregg <i>et al.</i> comparing arrays of prostatic epithelial (maroon) with interstitial stromal cell samples (teal) are depicted in panel e-h. a) Boxplot of raw intensities; b) density histogram of log intensities before normalization; c) density histogram of log intensities after normalization; d) MA-plot before (upper panel) and after normalization (lower panel) of one example array of the dataset by Varambally <i>et al.</i>; e) boxplot of raw intensities; f) density histogram of log intensities before normalization; g) density histogram of log intensities after normalization; h) MA-plot before (upper panel) and after normalization (lower panel) of one example array of the dataset by Gregg <i>et al.</i></p
A bioinformatics workflow to decipher transcriptomic data from vitamin D studies
The link between the experimental laboratory studies and bioinformatic approaches aims to find procedures to connect tools from both branches producing workflows that bring together different techniques that are capable of exploiting data at many levels. Thanks to the open access sources and the numerous tools available, it is possible to create various pipelines capable of solving specific problems. Nevertheless the lack of connectivity between them that interconnect different approaches complicates the exploitation of these workflows. Here, we present a detailed description of a workflow composed of different bioinformatics tools that exploits data from large-scale gene expression experiments, contextualizing them at many biological levels. To illustrate the relevance of our workflow for the vitamin D community we applied it to data from myeloid cell models treated with the hormonally active form of vitamin. From raw files of functional genomic studies it is possible to utilize the whole information to obtain a biological insight. Different software and algorithms are included to analyse at pathway, metabolic, ontology and molecular biology level the effects on gene expression. The usage of different databases to analyse gene expression data allows to perform a complete interpretation of functional genomic studies and the implementation of analysis and visualization software tools gives a better understanding of the biological meaning of the results. This review is an example of how to select and bring together several software modules to create one pipeline that processes and analyses genomic data at many biological levels making it open, reproducible and user friendly. Finally, the application of our bioinformatic pipeline revealed that vitamin D modulates crucial metabolic pathways in different myeloid cells that may play an important role in their immune function
Integrated analysis of human transcriptome data for Rett syndrome finds a network of involved genes
Objectives: Rett syndrome (RTT) is a rare disorder causing severe intellectual and physical disability. The cause is a mutation in the gene coding for the methyl-CpG binding protein 2 (MECP2), a multifunctional regulator protein. Purpose of the study was integration and investigation of multiple gene expression profiles in human cells with impaired MECP2 gene to obtain a robust, data-driven insight in molecular disease mechanisms. Methods: Information about changed gene expression was extracted from five previously published studies, integrated and the resulting differentially expressed genes were analysed using overrepresentation analysis of biological pathways and gene ontology, and network analysis. Results: We identified a set of genes, which are significantly changed not in all but several transcriptomics datasets and were not mentioned in the context of RTT before. We found that these genes are involved in several processes and molecular pathways known to be affected in RTT. Integrating transcription factors we identified a possible link how MECP2 regulates cytoskeleton organisation via MEF2C and CAPG. Conclusions: Integrative analysis of omics data and prior knowledge databases is a powerful approach to identify links between mutation and phenotype especially in rare disease research where little data is available.</p
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