Whole blood RNA sequencing identifies transcriptional differences between primary sclerosing cholangitis and ulcerative colitis
Background & Aims: Genetic and microbiome studies across patients with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC) have indicated that UC in PSC is a separate disease entity to primary UC, but expression studies for PSC are lacking. Methods: We conducted whole blood RNA...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-02-01
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| Series: | JHEP Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589555923003191 |
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| author | Eike Matthias Wacker Florian Uellendahl-Werth Saptarshi Bej Olaf Wolkenhauer Mette Vesterhus Wolfgang Lieb Andre Franke Tom Hemming Karlsen Trine Folseraas David Ellinghaus |
| author_facet | Eike Matthias Wacker Florian Uellendahl-Werth Saptarshi Bej Olaf Wolkenhauer Mette Vesterhus Wolfgang Lieb Andre Franke Tom Hemming Karlsen Trine Folseraas David Ellinghaus |
| author_sort | Eike Matthias Wacker |
| collection | DOAJ |
| description | Background & Aims: Genetic and microbiome studies across patients with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC) have indicated that UC in PSC is a separate disease entity to primary UC, but expression studies for PSC are lacking. Methods: We conducted whole blood RNA sequencing experiments for 495 patients with UC, 220 patients with PSC (including 177 with UC), and 320 healthy controls from Germany and Norway. Differential expression analyses, gene ontology and coexpression analyses and random forest machine learning were performed to identify genes, ontologies and transcriptional features that discriminate diagnoses. Results: The blood transcriptome in UC and PSC is dominated by neutrophil activation genes (e.g. S100A12). In UC, but not in PSC (neither PSC alone nor patients with an additional diagnosis of UC [PSC/UC]), ribosomal, mitochondrial, and energy metabolism genes are upregulated in conjunction with antibody transcript expression (MZB1, IGJ). In PSC, there is an increase in modules related to apoptosis and expression of genes of interferon-I-related ontologies. Random forest analysis could poorly discriminate PSC alone from PSC/UC (AUROC 0.56), but could discriminate PSC, UC, and controls with high accuracy (AUROC UC vs. controls 0.95, PSC vs. controls 0.88, UC vs. PSC 0.986). The main coexpression modules relevant for distinguishing PSC, UC, and controls are enriched in neutrophil degranulation and antibody production genes. Conclusions: Supported by machine learning results, PSC and UC appear to be separate entities on a molecular level, while PSC/UC and PSC are indistinguishable. Impact and implications: Clinical and genetic studies suggest that the colitis-like symptoms in primary sclerosing cholangitis (PSC) represent a different disease entity from primary ulcerative colitis (UC). The present study supports this assumption with transcriptomic data from whole blood and describes notable differences in gene expression between primary UC and PSC, providing insights into the still unclear pathophysiology of both diseases. These findings are of interest to scientists seeking to decipher the molecular pathophysiology of both diseases and provide evidence that a redefinition of the PSC-UC phenotype should be considered. The study practically supports future molecular research by providing a large transcriptomic whole blood reference cohort. |
| first_indexed | 2024-03-08T04:51:06Z |
| format | Article |
| id | doaj.art-e621b389973f46bcb8be965ca0328d62 |
| institution | Directory Open Access Journal |
| issn | 2589-5559 |
| language | English |
| last_indexed | 2024-03-08T04:51:06Z |
| publishDate | 2024-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JHEP Reports |
| spelling | doaj.art-e621b389973f46bcb8be965ca0328d622024-02-08T05:13:42ZengElsevierJHEP Reports2589-55592024-02-0162100988Whole blood RNA sequencing identifies transcriptional differences between primary sclerosing cholangitis and ulcerative colitisEike Matthias Wacker0Florian Uellendahl-Werth1Saptarshi Bej2Olaf Wolkenhauer3Mette Vesterhus4Wolfgang Lieb5Andre Franke6Tom Hemming Karlsen7Trine Folseraas8David Ellinghaus9Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, GermanyInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, GermanyDepartment of Systems Biology and Bioinformatics, University of Rostock, Rostock, Germany; Indian Institute of Science Education and Research, Thiruvananthapuram, IndiaDepartment of Systems Biology and Bioinformatics, University of Rostock, Rostock, Germany; Leibniz-Institute for Food Systems Biology at the Technical University Munich, Munich, Germany; Stellenbosch Institute for Advanced Study (STIAS), Wallenberg Research Centre at Stellenbosch University, Stellenbosch, South AfricaNorwegian PSC Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet and University of Oslo, Oslo, Norway; Department of Medicine, Haraldsplass Deaconess Hospital, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, NorwayInstitute of Epidemiology, Christian-Albrechts-University of Kiel, Kiel, GermanyInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, GermanyResearch Institute for Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet and University of Oslo, Oslo, NorwayResearch Institute for Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet and University of Oslo, Oslo, NorwayInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany; Corresponding author. Address: Institute of Clinical Molecular Biology (IKMB), Kiel University (CAU) and University Medical Center Schleswig-Holstein (USKH), Rosalind-Franklin-Str. 12, 24105 Kiel, Germany.Background & Aims: Genetic and microbiome studies across patients with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC) have indicated that UC in PSC is a separate disease entity to primary UC, but expression studies for PSC are lacking. Methods: We conducted whole blood RNA sequencing experiments for 495 patients with UC, 220 patients with PSC (including 177 with UC), and 320 healthy controls from Germany and Norway. Differential expression analyses, gene ontology and coexpression analyses and random forest machine learning were performed to identify genes, ontologies and transcriptional features that discriminate diagnoses. Results: The blood transcriptome in UC and PSC is dominated by neutrophil activation genes (e.g. S100A12). In UC, but not in PSC (neither PSC alone nor patients with an additional diagnosis of UC [PSC/UC]), ribosomal, mitochondrial, and energy metabolism genes are upregulated in conjunction with antibody transcript expression (MZB1, IGJ). In PSC, there is an increase in modules related to apoptosis and expression of genes of interferon-I-related ontologies. Random forest analysis could poorly discriminate PSC alone from PSC/UC (AUROC 0.56), but could discriminate PSC, UC, and controls with high accuracy (AUROC UC vs. controls 0.95, PSC vs. controls 0.88, UC vs. PSC 0.986). The main coexpression modules relevant for distinguishing PSC, UC, and controls are enriched in neutrophil degranulation and antibody production genes. Conclusions: Supported by machine learning results, PSC and UC appear to be separate entities on a molecular level, while PSC/UC and PSC are indistinguishable. Impact and implications: Clinical and genetic studies suggest that the colitis-like symptoms in primary sclerosing cholangitis (PSC) represent a different disease entity from primary ulcerative colitis (UC). The present study supports this assumption with transcriptomic data from whole blood and describes notable differences in gene expression between primary UC and PSC, providing insights into the still unclear pathophysiology of both diseases. These findings are of interest to scientists seeking to decipher the molecular pathophysiology of both diseases and provide evidence that a redefinition of the PSC-UC phenotype should be considered. The study practically supports future molecular research by providing a large transcriptomic whole blood reference cohort.http://www.sciencedirect.com/science/article/pii/S2589555923003191RNA-SeqGene Expression ProfilingPrimary sclerosingCholangitisUlcerativeColitisTranscriptomeWhole blood |
| spellingShingle | Eike Matthias Wacker Florian Uellendahl-Werth Saptarshi Bej Olaf Wolkenhauer Mette Vesterhus Wolfgang Lieb Andre Franke Tom Hemming Karlsen Trine Folseraas David Ellinghaus Whole blood RNA sequencing identifies transcriptional differences between primary sclerosing cholangitis and ulcerative colitis JHEP Reports RNA-Seq Gene Expression Profiling Primary sclerosingCholangitis UlcerativeColitis Transcriptome Whole blood |
| title | Whole blood RNA sequencing identifies transcriptional differences between primary sclerosing cholangitis and ulcerative colitis |
| title_full | Whole blood RNA sequencing identifies transcriptional differences between primary sclerosing cholangitis and ulcerative colitis |
| title_fullStr | Whole blood RNA sequencing identifies transcriptional differences between primary sclerosing cholangitis and ulcerative colitis |
| title_full_unstemmed | Whole blood RNA sequencing identifies transcriptional differences between primary sclerosing cholangitis and ulcerative colitis |
| title_short | Whole blood RNA sequencing identifies transcriptional differences between primary sclerosing cholangitis and ulcerative colitis |
| title_sort | whole blood rna sequencing identifies transcriptional differences between primary sclerosing cholangitis and ulcerative colitis |
| topic | RNA-Seq Gene Expression Profiling Primary sclerosingCholangitis UlcerativeColitis Transcriptome Whole blood |
| url | http://www.sciencedirect.com/science/article/pii/S2589555923003191 |
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