Multiomic Sequencing Reveals Distinctive Gene Expression and Epigenetic Alterations Associated With Primary Sclerosing Cholangitis Development in Treatment-Naïve Pediatric Ulcerative Colitis
Our study, for the first time, identifies distinct gene expression and DNA methylation alterations that differentiate UC from PSC-UC at diagnosis in treatment-naïve pediatric patients. We show the gene expression differences observed between PSC-UC and UC are modulated by intricate molecular mechanisms involving master transcriptional regulator-mediated signaling through transcription factors. These findings suggest the potential utility of these molecular markers as predictive biomarkers for PSC development in UC at an early stage of development. Further validation in larger patient cohorts is warranted.
Authors
- Alexander Kel (ORCID: https://orcid.org/0000-0001-6775-2467)
- Ciarán McDonnell (ORCID: https://orcid.org/0000-0001-9492-2791)
- Glen A. Doherty (ORCID: https://orcid.org/0000-0003-4384-5049)
- Róisín Stack (ORCID: https://orcid.org/0000-0002-0519-5949)
- Gráinne Kirwan (ORCID: https://orcid.org/0000-0001-6011-5510)
- Séamus Hussey (ORCID: https://orcid.org/0000-0002-9362-0465)
- Ian Stephens (ORCID: https://orcid.org/0000-0001-5097-4602)
- John O’Brien (ORCID: https://orcid.org/0000-0002-0270-3442)
- Flavia Genua (ORCID: https://orcid.org/0000-0003-3724-7122)
- Anna Dominik
- Muhammad Ali (ORCID: https://orcid.org/0000-0003-4742-425X)
- Gregory S. Yochum (ORCID: https://orcid.org/0000-0002-1211-3040)
- Luke Grant
- Alejandra Rodríguez-Sosa
- Michael McDermot
- Sudipto Das (ORCID: https://orcid.org/0009-0000-8325-0088)
- Ololade Lawal
Institutions
- Pennsylvania State University (US)
- Royal College of Surgeons in Ireland (IE)
- Children's Health Ireland at Crumlin (IE)
- St. Vincent's University Hospital (IE)
- GeneXplain (Germany) (DE)
- Penn State Milton S. Hershey Medical Center (US)
Publication Details
- Journal
- Gastro Hep Advances
- Published
- 2024-11-15
- DOI
- https://doi.org/10.1016/j.gastha.2024.11.002
- Citations
- 1
- Primary Topic
- Liver Diseases and Immunity
- Type
- article
- Field-Weighted Citation Impact
- 0.37
Funders
- Royal College of Surgeons in Ireland
- Ireland Funds
- European Crohn's and Colitis Organisation
- Enterprise Ireland
- Science Foundation Ireland
- Irish Research Council
- H2020 Marie Skłodowska-Curie Actions