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scDrugPrio: a frame...
scDrugPrio: a framework for the analysis of single-cell transcriptomics to address multiple problems in precision medicine in immune-mediated inflammatory diseases
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- Schäfer, Samuel (författare)
- Linköpings universitet,Avdelningen för barns och kvinnors hälsa,Medicinska fakulteten,Region Östergötland, Mag- tarmmedicinska kliniken,Centre for Personalised Medicine
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- Smelik, Martin (författare)
- Karolinska Institutet
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- Sysoev, Oleg, 1981- (författare)
- Linköpings universitet,Statistik och maskininlärning,Filosofiska fakulteten
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- Zhao, Yelin (författare)
- Karolinska Inst, Sweden
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- Eklund, Desiré (författare)
- Linköpings universitet,Avdelningen för neurobiologi,Medicinska fakulteten,Centre for Personalised Medicine
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- Lilja, Sandra (författare)
- Linköpings universitet,Avdelningen för barns och kvinnors hälsa,Medicinska fakulteten,Mavatar Inc, Sweden,Centre for Personalised Medicine
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- Gustafsson, Mika (författare)
- Linköpings universitet,Bioinformatik,Tekniska fakulteten
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- Heyn, Holger (författare)
- Barcelona Inst Sci & Technol BIST, Spain; Univ Pompeu Fabra UPF, Spain
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- Julia, Antonio (författare)
- Inst Recerca Vall dHebron, Spain
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- Kovacs, Istvan A. (författare)
- Northwestern Univ, IL 60208 USA; Northwestern Univ, IL 60208 USA
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- Loscalzo, Joseph (författare)
- Brigham & Womens Hosp, MA USA
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- Marsal, Sara (författare)
- Inst Recerca Vall dHebron, Spain
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- Zhang, Huan (författare)
- Linköpings universitet,Avdelningen för barns och kvinnors hälsa,Medicinska fakulteten,Centre for Personalised Medicine
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- Li, Xinxiu (författare)
- Karolinska Inst, Sweden
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- Gawel, Danuta (författare)
- Mavatar Inc, Sweden
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- Wang, Hui (författare)
- Karolinska Inst, Sweden; Xuzhou Med Univ, Peoples R China
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- Benson, Mikael (författare)
- Karolinska Inst, Sweden
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(creator_code:org_t)
- BMC, 2024
- 2024
- Engelska.
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Ingår i: Genome Medicine. - : BMC. - 1756-994X. ; 16:1
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- Background Ineffective drug treatment is a major problem for many patients with immune-mediated inflammatory diseases (IMIDs). Important reasons are the lack of systematic solutions for drug prioritisation and repurposing based on characterisation of the complex and heterogeneous cellular and molecular changes in IMIDs.Methods Here, we propose a computational framework, scDrugPrio, which constructs network models of inflammatory disease based on single-cell RNA sequencing (scRNA-seq) data. scDrugPrio constructs detailed network models of inflammatory diseases that integrate information on cell type-specific expression changes, altered cellular crosstalk and pharmacological properties for the selection and ranking of thousands of drugs.Results scDrugPrio was developed using a mouse model of antigen-induced arthritis and validated by improved precision/recall for approved drugs, as well as extensive in vitro, in vivo, and in silico studies of drugs that were predicted, but not approved, for the studied diseases. Next, scDrugPrio was applied to multiple sclerosis, Crohn's disease, and psoriatic arthritis, further supporting scDrugPrio through prioritisation of relevant and approved drugs. However, in contrast to the mouse model of arthritis, great interindividual cellular and gene expression differences were found in patients with the same diagnosis. Such differences could explain why some patients did or did not respond to treatment. This explanation was supported by the application of scDrugPrio to scRNA-seq data from eleven individual Crohn's disease patients. The analysis showed great variations in drug predictions between patients, for example, assigning a high rank to anti-TNF treatment in a responder and a low rank in a nonresponder to that treatment.Conclusions We propose a computational framework, scDrugPrio, for drug prioritisation based on scRNA-seq of IMID disease. Application to individual patients indicates scDrugPrio's potential for personalised network-based drug screening on cellulome-, genome-, and drugome-wide scales. For this purpose, we made scDrugPrio into an easy-to-use R package (https://github.com/SDTC-CPMed/scDrugPrio).
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Nyckelord
- Single-cell RNA sequencing; scRNA-seq; Immune-mediated inflammatory disease; Drug prioritisation; Drug repurposing; Drug prediction
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
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Schäfer, Samuel
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Smelik, Martin
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Sysoev, Oleg, 19 ...
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Zhao, Yelin
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Eklund, Desiré
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Lilja, Sandra
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visa fler...
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Gustafsson, Mika
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Heyn, Holger
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Julia, Antonio
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Kovacs, Istvan A ...
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Loscalzo, Joseph
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Marsal, Sara
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Zhang, Huan
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Li, Xinxiu
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Gawel, Danuta
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Wang, Hui
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Benson, Mikael
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Farmakologi och ...
- Artiklar i publikationen
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Genome Medicine
- Av lärosätet
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Linköpings universitet
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Karolinska Institutet