Search: onr:"swepub:oai:gup.ub.gu.se/285601" > A validated single-...
Fältnamn | Indikatorer | Metadata |
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000 | 09329naa a2200829 4500 | |
001 | oai:gup.ub.gu.se/285601 | |
003 | SwePub | |
008 | 240528s2019 | |||||||||||000 ||eng| | |
009 | oai:prod.swepub.kib.ki.se:141458002 | |
009 | oai:DiVA.org:liu-159568 | |
024 | 7 | a https://gup.ub.gu.se/publication/2856012 URI |
024 | 7 | a https://doi.org/10.1186/s13073-019-0657-32 DOI |
024 | 7 | a http://kipublications.ki.se/Default.aspx?queryparsed=id:1414580022 URI |
024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-1595682 URI |
040 | a (SwePub)gud (SwePub)kid (SwePub)liu | |
041 | a eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Gawel, Danutau Linköpings universitet,Avdelningen för barns och kvinnors hälsa,Medicinska fakulteten4 aut0 (Swepub:liu)danga10 |
245 | 1 0 | a A validated single-cell-based strategy to identify diagnostic and therapeutic targets in complex diseases |
264 | c 2019-07-30 | |
264 | 1 | b Springer Science and Business Media LLC,c 2019 |
500 | a Funding Agencies|Swedish Cancer Foundation [17 0542, 15 0532]; European Commission [305033]; Swedish Research Council [2015-02575, 2015-03495, 2015-03807]; Clinical Cancer Research, Jonkoping, Sweden; Torsten Soderberg Foundation; East Gothia Regional Funding | |
520 | a Background: Genomic medicine has paved the way for identifying biomarkers and therapeutically actionable targets for complex diseases, but is complicated by the involvement of thousands of variably expressed genes across multiple cell types. Single-cell RNA-sequencing study (scRNA-seq) allows the characterization of such complex changes in whole organs. Methods: The study is based on applying network tools to organize and analyze scRNA-seq data from a mouse model of arthritis and human rheumatoid arthritis, in order to find diagnostic biomarkers and therapeutic targets. Diagnostic validation studies were performed using expression profiling data and potential protein biomarkers from prospective clinical studies of 13 diseases. A candidate drug was examined by a treatment study of a mouse model of arthritis, using phenotypic, immunohistochemical, and cellular analyses as read-outs. Results: We performed the first systematic analysis of pathways, potential biomarkers, and drug targets in scRNA-seq data from a complex disease, starting with inflamed joints and lymph nodes from a mouse model of arthritis. We found the involvement of hundreds of pathways, biomarkers, and drug targets that differed greatly between cell types. Analyses of scRNA-seq and GWAS data from human rheumatoid arthritis (RA) supported a similar dispersion of pathogenic mechanisms in different cell types. Thus, systems-level approaches to prioritize biomarkers and drugs are needed. Here, we present a prioritization strategy that is based on constructing network models of disease-associated cell types and interactions using scRNA-seq data from our mouse model of arthritis, as well as human RA, which we term multicellular disease models (MCDMs). We find that the network centrality of MCDM cell types correlates with the enrichment of genes harboring genetic variants associated with RA and thus could potentially be used to prioritize cell types and genes for diagnostics and therapeutics. We validated this hypothesis in a large-scale study of patients with 13 different autoimmune, allergic, infectious, malignant, endocrine, metabolic, and cardiovascular diseases, as well as a therapeutic study of the mouse arthritis model. Conclusions: Overall, our results support that our strategy has the potential to help prioritize diagnostic and therapeutic targets in human disease. | |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Medicinsk genetik0 (SwePub)301072 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Medical Genetics0 (SwePub)301072 hsv//eng |
653 | a Biomarker and drug discovery | |
653 | a Network tools | |
653 | a scRNA-seq | |
653 | a Network tools; scRNA-seq; Biomarker and drug discovery | |
700 | 1 | a Serra-Musach, Jordiu Linköpings universitet,Avdelningen för barns och kvinnors hälsa,Medicinska fakulteten4 aut0 (Swepub:liu)jorse51 |
700 | 1 | a Lilja, Sandrau Linköpings universitet,Avdelningen för barns och kvinnors hälsa,Medicinska fakulteten4 aut0 (Swepub:liu)sanli71 |
700 | 1 | a Aagesen, Jesperu Reg Jonkoping Cty, Sweden4 aut |
700 | 1 | a Arenas, Alexu Karolinska Institutet,Univ Rovira and Virgili, Spain4 aut |
700 | 1 | a Asking, Bengtu Reg Jonkoping Cty, Sweden4 aut |
700 | 1 | a Bengnér, Malinu Reg Jonkoping Cty, Sweden4 aut |
700 | 1 | a Björkander, Janneu Reg Jonkoping Cty, Sweden4 aut |
700 | 1 | a Biggs, Sophieu Linköpings universitet,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten4 aut0 (Swepub:liu)sopbi13 |
700 | 1 | a Ernerudh, Janu Linköpings universitet,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten,Region Östergötland, Klinisk immunologi och transfusionsmedicin4 aut0 (Swepub:liu)janer15 |
700 | 1 | a Hjortswang, Henriku Linköpings universitet,Medicinska fakulteten,Avdelningen för neuro- och inflammationsvetenskap,Region Östergötland, Magtarmmedicinska kliniken4 aut0 (Swepub:liu)henhj44 |
700 | 1 | a Karlsson, Jan-Eriku Linköpings universitet,Avdelningen för kardiovaskulär medicin,Medicinska fakulteten,Reg Jonkoping Cty, Sweden4 aut0 (Swepub:liu)janka97 |
700 | 1 | a Köpsén, Mattiasu Linköpings universitet,Bioinformatik,Tekniska fakulteten4 aut0 (Swepub:liu)n/a |
700 | 1 | a Jung Lee, Eun Jungu Linköpings universitet,Avdelningen för barns och kvinnors hälsa,Medicinska fakulteten,Yonsei Univ, South Korea4 aut0 (Swepub:liu)eunle80 |
700 | 1 | a Lentini, Antoniou Linköpings universitet,Avdelningen för barns och kvinnors hälsa,Medicinska fakulteten4 aut0 (Swepub:liu)antle32 |
700 | 1 | a Li, Xinxiuu Linköpings universitet,Avdelningen för barns och kvinnors hälsa,Medicinska fakulteten4 aut0 (Swepub:liu)xinli70 |
700 | 1 | a Magnusson, Mattiasu Linköpings universitet,Karolinska Institutet,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten4 aut0 (Swepub:liu)matma88 |
700 | 1 | a Martinez, Davidu Linköpings universitet,Bioinformatik,Tekniska fakulteten4 aut0 (Swepub:liu)davma27 |
700 | 1 | a Matussek, Andreasu Reg Jonkoping Cty, Sweden; Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden4 aut |
700 | 1 | a Nestor, Colmu Linköpings universitet,Avdelningen för barns och kvinnors hälsa,Medicinska fakulteten4 aut0 (Swepub:liu)colne37 |
700 | 1 | a Schäfer, Samuelu Linköpings universitet,Medicinska fakulteten,Avdelningen för barns och kvinnors hälsa4 aut0 (Swepub:liu)samsc76 |
700 | 1 | a Seifert, Oliveru Linköpings universitet,Avdelningen för cellbiologi,Medicinska fakulteten,Reg Jonkoping Cty, Sweden4 aut0 (Swepub:liu)olise96 |
700 | 1 | a Sonmez, Ceylanu Linköpings universitet,Avdelningen för läkemedelsforskning,Medicinska fakulteten4 aut0 (Swepub:liu)ceyso17 |
700 | 1 | a Stjernman, Henriku Reg Jonkoping Cty, Sweden4 aut |
700 | 1 | a Tjärnberg, Andreasu Linköpings universitet,Bioinformatik,Tekniska fakulteten4 aut0 (Swepub:liu)andtj33 |
700 | 1 | a Wu, Simonu Linköpings universitet,Bioinformatik,Tekniska fakulteten4 aut0 (Swepub:liu)n/a |
700 | 1 | a Åkesson, Karinu Linköpings universitet,Avdelningen för barns och kvinnors hälsa,Medicinska fakulteten,Reg Jonkoping Cty, Sweden4 aut0 (Swepub:liu)karak14 |
700 | 1 | a Shalek, Alex K.u MIT, MA 02139 USA; Broad Inst MIT and Harvard, MA 02142 USA; Ragon Inst MGH MIT and Harvard, MA USA4 aut |
700 | 1 | a Stenmarker, Margaretha,d 1960u Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för pediatrik,Institute of Clinical Sciences, Department of Pediatrics,Reg Jonkoping Cty, Sweden; Inst Clin Sci, Sweden4 aut0 (Swepub:gu)xstemp |
700 | 1 | a Zhang, Huanu Linköpings universitet,Avdelningen för barns och kvinnors hälsa,Medicinska fakulteten4 aut0 (Swepub:liu)huazh47 |
700 | 1 | a Gustafsson, Mikau Linköpings universitet,Bioinformatik,Tekniska fakulteten4 aut0 (Swepub:liu)mikgu75 |
700 | 1 | a Benson, Mikaelu Linköpings universitet,Avdelningen för barns och kvinnors hälsa,Medicinska fakulteten,Region Östergötland, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus4 aut0 (Swepub:liu)mikbe05 |
710 | 2 | a Linköpings universitetb Avdelningen för barns och kvinnors hälsa4 org |
773 | 0 | t Genome Medicined : Springer Science and Business Media LLCg 11q 11x 1756-994X |
856 | 4 | u https://genomemedicine.biomedcentral.com/track/pdf/10.1186/s13073-019-0657-3 |
856 | 4 | u https://doi.org/10.1186/s13073-019-0657-3y Fulltext |
856 | 4 | u http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-165944y Link to correction |
856 | 4 | u https://liu.diva-portal.org/smash/get/diva2:1342460/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print |
856 | 4 8 | u https://gup.ub.gu.se/publication/285601 |
856 | 4 8 | u https://doi.org/10.1186/s13073-019-0657-3 |
856 | 4 8 | u http://kipublications.ki.se/Default.aspx?queryparsed=id:141458002 |
856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-159568 |
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