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  1. AU="John P. Thomas"
  2. AU="Airton Massaro"
  3. AU="Isabelle Hautefort"

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  1. Artikel ; Online: Network Biology Approaches to Achieve Precision Medicine in Inflammatory Bowel Disease

    John P Thomas / Dezso Modos / Tamas Korcsmaros / Johanne Brooks-Warburton

    Frontiers in Genetics, Vol

    2021  Band 12

    Abstract: Inflammatory bowel disease (IBD) is a chronic immune-mediated condition arising due to complex interactions between multiple genetic and environmental factors. Despite recent advances, the pathogenesis of the condition is not fully understood and ... ...

    Abstract Inflammatory bowel disease (IBD) is a chronic immune-mediated condition arising due to complex interactions between multiple genetic and environmental factors. Despite recent advances, the pathogenesis of the condition is not fully understood and patients still experience suboptimal clinical outcomes. Over the past few years, investigators are increasingly capturing multi-omics data from patient cohorts to better characterise the disease. However, reaching clinically translatable endpoints from these complex multi-omics datasets is an arduous task. Network biology, a branch of systems biology that utilises mathematical graph theory to represent, integrate and analyse biological data through networks, will be key to addressing this challenge. In this narrative review, we provide an overview of various types of network biology approaches that have been utilised in IBD including protein-protein interaction networks, metabolic networks, gene regulatory networks and gene co-expression networks. We also include examples of multi-layered networks that have combined various network types to gain deeper insights into IBD pathogenesis. Finally, we discuss the need to incorporate other data sources including metabolomic, histopathological, and high-quality clinical meta-data. Together with more robust network data integration and analysis frameworks, such efforts have the potential to realise the key goal of precision medicine in IBD.
    Schlagwörter inflammatory bowel disease ; network biology ; protein-protein interaction network ; gene coexpression network ; multilayered network ; precision medicine ; Genetics ; QH426-470
    Thema/Rubrik (Code) 006
    Sprache Englisch
    Erscheinungsdatum 2021-10-01T00:00:00Z
    Verlag Frontiers Media S.A.
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  2. Artikel ; Online: Analysing miRNA-Target Gene Networks in Inflammatory Bowel Disease and Other Complex Diseases Using Transcriptomic Data

    John P. Thomas / Marton Ölbei / Johanne Brooks-Warburton / Tamas Korcsmaros / Dezso Modos

    Genes, Vol 13, Iss 370, p

    2022  Band 370

    Abstract: Patients with inflammatory bowel disease (IBD) are known to have perturbations in microRNA (miRNA) levels as well as altered miRNA regulation. Although experimental methods have provided initial insights into the functional consequences that may arise ... ...

    Abstract Patients with inflammatory bowel disease (IBD) are known to have perturbations in microRNA (miRNA) levels as well as altered miRNA regulation. Although experimental methods have provided initial insights into the functional consequences that may arise due to these changes, researchers are increasingly utilising novel bioinformatics approaches to further dissect the role of miRNAs in IBD. The recent exponential increase in transcriptomics datasets provides an excellent opportunity to further explore the role of miRNAs in IBD pathogenesis. To effectively understand miRNA-target gene interactions from gene expression data, multiple database resources are required, which have become available in recent years. In this technical note, we provide a step-by-step protocol for utilising these state-of-the-art resources, as well as systems biology approaches to understand the role of miRNAs in complex disease pathogenesis. We demonstrate through a case study example how to combine the resulting miRNA-target gene networks with transcriptomics data to find potential disease-specific miRNA regulators and miRNA-target genes in Crohn’s disease. This approach could help to identify miRNAs that may have important disease-modifying effects in IBD and other complex disorders, and facilitate the discovery of novel therapeutic targets.
    Schlagwörter miRNA ; network biology ; ulcerative colitis ; Crohn’s disease ; transcriptomics ; microarrays ; Genetics ; QH426-470
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2022-02-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  3. Artikel ; Online: CytokineLink

    Marton Olbei / John P. Thomas / Isabelle Hautefort / Agatha Treveil / Balazs Bohar / Matthew Madgwick / Lejla Gul / Luca Csabai / Dezso Modos / Tamas Korcsmaros

    Cells, Vol 10, Iss 2242, p

    A Cytokine Communication Map to Analyse Immune Responses—Case Studies in Inflammatory Bowel Disease and COVID-19

    2021  Band 2242

    Abstract: Intercellular communication mediated by cytokines is critical to the development of immune responses, particularly in the context of infectious and inflammatory diseases. By releasing these small molecular weight peptides, the source cells can influence ... ...

    Abstract Intercellular communication mediated by cytokines is critical to the development of immune responses, particularly in the context of infectious and inflammatory diseases. By releasing these small molecular weight peptides, the source cells can influence numerous intracellular processes in the target cells, including the secretion of other cytokines downstream. However, there are no readily available bioinformatic resources that can model cytokine–cytokine interactions. In this effort, we built a communication map between major tissues and blood cells that reveals how cytokine-mediated intercellular networks form during homeostatic conditions. We collated the most prevalent cytokines from the literature and assigned the proteins and their corresponding receptors to source tissue and blood cell types based on enriched consensus RNA-Seq data from the Human Protein Atlas database. To assign more confidence to the interactions, we integrated the literature information on cell–cytokine interactions from two systems of immunology databases, immuneXpresso and ImmunoGlobe. From the collated information, we defined two metanetworks: a cell–cell communication network connected by cytokines; and a cytokine–cytokine interaction network depicting the potential ways in which cytokines can affect the activity of each other. Using expression data from disease states, we then applied this resource to reveal perturbations in cytokine-mediated intercellular signalling in inflammatory and infectious diseases (ulcerative colitis and COVID-19, respectively). For ulcerative colitis, with CytokineLink, we demonstrated a significant rewiring of cytokine-mediated intercellular communication between non-inflamed and inflamed colonic tissues. For COVID-19, we were able to identify cell types and cytokine interactions following SARS-CoV-2 infection, highlighting important cytokine interactions that might contribute to severe illness in a subgroup of patients. Such findings have the potential to inform the development of novel, ...
    Schlagwörter cytokine ; network ; resource ; Cytoscape ; NDEx ; COVID-19 ; Biology (General) ; QH301-705.5
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2021-08-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  4. Artikel ; Online: A systems genomics approach to uncover patient-specific pathogenic pathways and proteins in ulcerative colitis

    Johanne Brooks-Warburton / Dezso Modos / Padhmanand Sudhakar / Matthew Madgwick / John P. Thomas / Balazs Bohar / David Fazekas / Azedine Zoufir / Orsolya Kapuy / Mate Szalay-Beko / Bram Verstockt / Lindsay J. Hall / Alastair Watson / Mark Tremelling / Miles Parkes / Severine Vermeire / Andreas Bender / Simon R. Carding / Tamas Korcsmaros

    Nature Communications, Vol 13, Iss 1, Pp 1-

    2022  Band 12

    Abstract: Single Nucleotide Polymorphisms (SNPs) affect cellular regulatory networks, and SNP co-occurrences contribute to disease pathogenesis in ulcerative colitis (UC). Here the authors introduce iSNP, a precision medicine pipeline that combines genomics and ... ...

    Abstract Single Nucleotide Polymorphisms (SNPs) affect cellular regulatory networks, and SNP co-occurrences contribute to disease pathogenesis in ulcerative colitis (UC). Here the authors introduce iSNP, a precision medicine pipeline that combines genomics and network biology approaches to uncover patient specific pathways affected in complex diseases.
    Schlagwörter Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2022-04-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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