ArticleGenome medicine2014
Integrated genomic and prospective clinical studies show the importance of modular pleiotropy for disease susceptibility, diagnosis and treatment.
Article in Genome medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 35 citations in OpenAlex.
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- Latent space arithmetic on data embeddings from healthy multi-tissue human RNA-seq decodes disease modules.Patterns (New York, N.Y.) · 2024Article
- CD4Epigenetics · 2022Article
- MODalyseR-a novel software for inference of disease module hub regulators identified a putative multiple sclerosis regulator supported by independent eQTL data.Bioinformatics advances · 2022Article
- RNA-sequencing and mass-spectrometry proteomic time-series analysis of T-cell differentiation identified multiple splice variants models that predicted validated protein biomarkers in inflammatory diseases.Frontiers in molecular biosciences · 2022Article
- Altered Expression of TSPAN32 during B Cell Activation and Systemic Lupus Erythematosus.Genes · 2021Article
- Profiling of inhibitory immune checkpoints in glioblastoma: Potential pathogenetic players.Oncology letters · 2020Article
- Impaired Expression of Tetraspanin 32 (TSPAN32) in Memory T Cells of Patients with Multiple Sclerosis.Brain sciences · 2020Article
- Modulation of Tetraspanin 32 (TSPAN32) Expression in T Cell-Mediated Immune Responses and in Multiple Sclerosis.International journal of molecular sciences · 2019Article
- Retrospective follow-up analysis of the transcriptomic patterns of cytokines, cytokine receptors and chemokines at preconception and during pregnancy, in women with post-partum depression.Experimental and therapeutic medicine · 2019Article
- Characterization of the Pathophysiological Role of CD47 in Uveal Melanoma.Molecules (Basel, Switzerland) · 2019Article
- Identification of CD4+ T cell biomarkers for predicting the response of patients with relapsing‑remitting multiple sclerosis to natalizumab treatment.Molecular medicine reports · 2019Article
- Module-detection approaches for the integration of multilevel omics data highlight the comprehensive response of Aspergillus fumigatus to caspofungin.BMC systems biology · 2018Article
- ModuleDiscoverer: Identification of regulatory modules in protein-protein interaction networks.Scientific reports · 2018Article
- Biomechanisms of Comorbidity: Reviewing Integrative Analyses of Multi-omics Datasets and Electronic Health Records.Yearbook of medical informatics · 2016Review
- Gene signature-based mapping of immunological systems and diseases.BMC bioinformatics · 2016Article
- Identifying module biomarker in type 2 diabetes mellitus by discriminative area of functional activity.BMC bioinformatics · 2015Article
- Modules, networks and systems medicine for understanding disease and aiding diagnosis.Genome medicine · 2014Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTranslational research typically aims to identify and functionally validate individual, disease-specific genes. However, reaching this aim is complicated by the involvement of thousands of genes in common diseases, and that many of those genes are pleiotropic, that is, shared by several diseases.
methodsWe integrated genomic meta-analyses with prospective clinical studies to systematically investigate the pathogenic, diagnostic and therapeutic roles of pleiotropic genes. In a novel approach, we first used pathway analysis of all published genome-wide association studies (GWAS) to find a cell type common to many diseases.
resultsThe analysis showed over-representation of the T helper cell differentiation pathway, which is expressed in T cells. This led us to focus on expression profiling of CD4(+) T cells from highly diverse inflammatory and malignant diseases. We found that pleiotropic genes were highly interconnected and formed a pleiotropic module, which was enriched for inflammatory, metabolic and proliferative pathways. The general relevance of this module was supported by highly significant enrichment of genetic variants identified by all GWAS and cancer studies, as well as known diagnostic and therapeutic targets. Prospective clinical studies of multiple sclerosis and allergy showed the importance of both pleiotropic and disease specific modules for clinical stratification.
conclusionsIn summary, this translational genomics study identified a pleiotropic module, which has key pathogenic, diagnostic and therapeutic roles.
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Registered trials
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