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A validated gene regulatory network and GWAS identifies early regulators of T cell-associated diseases

Gustafsson, Mika (författare)
Linköpings universitet,Bioinformatik,Tekniska fakulteten,The Centre for Individualised Medicine, Department of Clinical and Experimental Medicine, Division of Pediatrics, Linköping University, Linköping, Sweden; Bioinformatics, Department of Physics, Chemistry, and Biology, Linköping University, Linköping, Sweden
Gawel, Danuta (författare)
Linköpings universitet,Avdelningen för kliniska vetenskaper,Medicinska fakulteten,The Centre for Individualised Medicine, Department of Clinical and Experimental Medicine, Division of Pediatrics, Linköping University, Linköping, Sweden
Alfredsson, Lars (författare)
Karolinska Institutet
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Baranzini, Sergio (författare)
University of Calif San Francisco, CA, USA,Department of Neurology, University of California, San Francisco, CA, USA
Bjorkander, Janne (författare)
Futurum-Academy for Health and Care, County Council of Jönköping, Jönköping, Sweden
Blomgran, Robert (författare)
Linköpings universitet,Avdelningen för mikrobiologi och molekylär medicin,Medicinska fakulteten,Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine, Linköping University, Linköping, Sweden
Hellberg, Sandra (författare)
Linköpings universitet,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten,Department of Clinical and Experimental Medicine, Division of Clinical Immunology, Unit of Autoimmunity and Immune Regulation, Linköping University, Linköping, Sweden
Eklund, Daniel (författare)
Linköpings universitet,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten,Department of Clinical Immunology and Transfusion Medicine, Linköping University, Linköping, Sweden
Ernerudh, Jan (författare)
Linköpings universitet,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten,Region Östergötland, Klinisk immunologi och transfusionsmedicin,Department of Clinical and Experimental Medicine, Division of Clinical Immunology, Unit of Autoimmunity and Immune Regulation, Linköping University, Linköping, Sweden; Department of Clinical Immunology and Transfusion Medicine, Linköping University, Linköping, Sweden
Kockum, Ingrid (författare)
Karolinska Institutet
Konstantinell, Aelita (författare)
Linköpings universitet,Medicinska fakulteten,Avdelningen för kliniska vetenskaper,The Centre for Individualised Medicine, Department of Clinical and Experimental Medicine, Division of Pediatrics, Linköping University, Linköping, Sweden; Department of Medical Biology, The Arctic University of Norway, Tromsø, Norway
Lahesmaa, Riita (författare)
Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland
Lentini, Antonio (författare)
Linköpings universitet,Avdelningen för kliniska vetenskaper,Medicinska fakulteten,The Centre for Individualised Medicine, Department of Clinical and Experimental Medicine, Division of Pediatrics, Linköping University, Linköping, Sweden
Liljenström, H. Robert I. (författare)
Linköpings universitet,Avdelningen för kliniska vetenskaper,Medicinska fakulteten,The Centre for Individualised Medicine, Department of Clinical and Experimental Medicine, Division of Pediatrics, Linköping University, Linköping, Sweden
Mattson, Lina (författare)
Linköpings universitet,Avdelningen för kliniska vetenskaper,Medicinska fakulteten,The Centre for Individualised Medicine, Department of Clinical and Experimental Medicine, Division of Pediatrics, Linköping University, Linköping, Sweden
Matussek, Andreas (författare)
Futurum-Academy for Health and Care, County Council of Jönköping, Jönköping, Sweden
Mellergård, Johan (författare)
Linköpings universitet,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten,Region Östergötland, Neurologiska kliniken i Linköping,Department of Neurology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
Mendez, Melissa (författare)
University of Peruana Cayetano Heredia, Peru,Laboratorio de Investigación en Enfermedades Infecciosas, LID, Universidad Peruana Cayetano Heredia, Lima, Peru
Olsson, Tomas (författare)
Karolinska Institutet
Pujana, Miguel A. (författare)
Catalan Institute Oncol, Spain,Program Against Cancer Therapeutic Resistance (ProCURE), Cancer and Systems Biology Unit, Catalan Institute of Oncology, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain
Rasool, Omid (författare)
Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland
Serra-Musach, Jordi (författare)
Catalan Institute Oncol, Spain,Program Against Cancer Therapeutic Resistance (ProCURE), Cancer and Systems Biology Unit, Catalan Institute of Oncology, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain
Stenmarker, Margaretha (författare)
Futurum-Academy for Health and Care, County Council of Jönköping, Jönköping, Sweden
Tripathi, Subhash (författare)
Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland
Viitala, Miro (författare)
Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland
Wang, Hui (författare)
Linköpings universitet,Avdelningen för kliniska vetenskaper,Medicinska fakulteten,University of Texas MD Anderson Cancer Centre, TX 77030 USA,The Centre for Individualised Medicine, Department of Clinical and Experimental Medicine, Division of Pediatrics, Linköping University, Linköping, Sweden; Department of Immunology, MD Anderson Cancer Center, Houston, TX, USA
Zhang, Huan (författare)
Linköpings universitet,Avdelningen för kliniska vetenskaper,Medicinska fakulteten,The Centre for Individualised Medicine, Department of Clinical and Experimental Medicine, Division of Pediatrics, Linköping University, Linköping, Sweden
Nestor, Colm (författare)
Linköpings universitet,Avdelningen för kliniska vetenskaper,Medicinska fakulteten,The Centre for Individualised Medicine, Department of Clinical and Experimental Medicine, Division of Pediatrics, Linköping University, Linköping, Sweden
Benson, Mikael (författare)
Linköpings universitet,Avdelningen för kliniska vetenskaper,Medicinska fakulteten,Region Östergötland, Allergicentrum US,The Centre for Individualised Medicine, Department of Clinical and Experimental Medicine, Division of Pediatrics, Linköping University, Linköping, Sweden
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 (creator_code:org_t)
AMER ASSOC ADVANCEMENT SCIENCE, 2015
2015
Engelska.
Ingår i: Science Translational Medicine. - : AMER ASSOC ADVANCEMENT SCIENCE. - 1946-6234 .- 1946-6242. ; 7:313
Relaterad länk:
https://liu.diva-por... (primary) (Raw object)
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http://liu.diva-port...
https://urn.kb.se/re...
https://doi.org/10.1...
https://urn.kb.se/re...
http://kipublication...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • Early regulators of disease may increase understanding of disease mechanisms and serve as markers for presymptomatic diagnosis and treatment. However, early regulators are difficult to identify because patients generally present after they are symptomatic. We hypothesized that early regulators of T cell-associated diseases could be found by identifying upstream transcription factors (TFs) in T cell differentiation and by prioritizing hub TFs that were enriched for disease-associated polymorphisms. A gene regulatory network (GRN) was constructed by time series profiling of the transcriptomes and methylomes of human CD4(+) T cells during in vitro differentiation into four helper T cell lineages, in combination with sequence-based TF binding predictions. The TFs GATA3, MAF, and MYB were identified as early regulators and validated by ChIP-seq (chromatin immunoprecipitation sequencing) and small interfering RNA knockdowns. Differential mRNA expression of the TFs and their targets in T cell-associated diseases supports their clinical relevance. To directly test if the TFs were altered early in disease, T cells from patients with two T cell-mediated diseases, multiple sclerosis and seasonal allergic rhinitis, were analyzed. Strikingly, the TFs were differentially expressed during asymptomatic stages of both diseases, whereas their targets showed altered expression during symptomatic stages. This analytical strategy to identify early regulators of disease by combining GRNs with genome-wide association studies may be generally applicable for functional and clinical studies of early disease development.

Ämnesord

NATURVETENSKAP  -- Biologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Infectious Medicine (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

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