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Inferring upstream regulatory genes of FOXP3 in human regulatory T cells from time-series transcriptomic data

Magni, Stefano (författare)
Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Belvaux, Luxembourg
Sawlekar, Rucha (författare)
Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Belvaux, Luxembourg
Capelle, Christophe M. (författare)
Department of Infection and Immunity, Luxembourg Institute of Health, Esch-Sur-Alzette, Luxembourg; Faculty of Science, Technology and Medicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
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Tslaf, Vera (författare)
Department of Infection and Immunity, Luxembourg Institute of Health, Esch-Sur-Alzette, Luxembourg; Faculty of Science, Technology and Medicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg; Transversal Translational Medicine, Luxembourg Institute of Health, Strassen, Luxembourg
Baron, Alexandre (författare)
Department of Infection and Immunity, Luxembourg Institute of Health, Esch-Sur-Alzette, Luxembourg
Zeng, Ni (författare)
Department of Infection and Immunity, Luxembourg Institute of Health, Esch-Sur-Alzette, Luxembourg
Mombaerts, Laurent (författare)
Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Belvaux, Luxembourg
Yue, Zuogong (författare)
Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Belvaux, Luxembourg
Yuan, Ye (författare)
School of Artificial Intelligence and Automation, Huazhong University of Science and Technology, Wuhan, China
Hefeng, Feng Q. (författare)
Department of Infection and Immunity, Luxembourg Institute of Health, Esch-Sur-Alzette, Luxembourg
Gonçalves, Jorge (författare)
Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Belvaux, Luxembourg; Department of Plant Sciences, University of Cambridge, Cambridge, United Kingdom
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 (creator_code:org_t)
Springer Nature, 2024
2024
Engelska.
Ingår i: npj Systems Biology and Applications. - : Springer Nature. - 2056-7189. ; 10:1
Relaterad länk:
https://doi.org/10.1...
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https://ltu.diva-por... (primary) (Raw object)
https://urn.kb.se/re...
https://doi.org/10.1...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • The discovery of upstream regulatory genes of a gene of interest still remains challenging. Here we applied a scalable computational method to unbiasedly predict candidate regulatory genes of critical transcription factors by searching the whole genome. We illustrated our approach with a case study on the master regulator FOXP3 of human primary regulatory T cells (Tregs). While target genes of FOXP3 have been identified, its upstream regulatory machinery still remains elusive. Our methodology selected five top-ranked candidates that were tested via proof-of-concept experiments. Following knockdown, three out of five candidates showed significant effects on the mRNA expression of FOXP3 across multiple donors. This provides insights into the regulatory mechanisms modulating FOXP3 transcriptional expression in Tregs. Overall, at the genome level this represents a high level of accuracy in predicting upstream regulatory genes of key genes of interest.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)

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