Multi-omics analysis in inclusion body myositis identifies mir-16 responsible for HLA overexpression
Abstract Background Inclusion Body Myositis is an acquired muscle disease. Its pathogenesis is unclear due to the co-existence of inflammation, muscle degeneration and mitochondrial dysfunction. We aimed to provide a more advanced understanding of the disease by combining multi-omics analysis with p...
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BMC
2025-01-01
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| Series: | Orphanet Journal of Rare Diseases |
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| Online Access: | https://doi.org/10.1186/s13023-024-03526-x |
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| author | Daphne Wijnbergen Mridul Johari Ozan Ozisik Peter A.C. ‘t Hoen Friederike Ehrhart Anaïs Baudot Chris T. Evelo Bjarne Udd Marco Roos Eleni Mina |
| author_facet | Daphne Wijnbergen Mridul Johari Ozan Ozisik Peter A.C. ‘t Hoen Friederike Ehrhart Anaïs Baudot Chris T. Evelo Bjarne Udd Marco Roos Eleni Mina |
| author_sort | Daphne Wijnbergen |
| collection | DOAJ |
| description | Abstract Background Inclusion Body Myositis is an acquired muscle disease. Its pathogenesis is unclear due to the co-existence of inflammation, muscle degeneration and mitochondrial dysfunction. We aimed to provide a more advanced understanding of the disease by combining multi-omics analysis with prior knowledge. We applied molecular subnetwork identification to find highly interconnected subnetworks with a high degree of change in Inclusion Body Myositis. These could be used as hypotheses for potential pathomechanisms and biomarkers that are implicated in this disease. Results Our multi-omics analysis resulted in five subnetworks that exhibit changes in multiple omics layers. These subnetworks are related to antigen processing and presentation, chemokine-mediated signaling, immune response-signal transduction, rRNA processing, and mRNA splicing. An interesting finding is that the antigen processing and presentation subnetwork links the underexpressed miR-16-5p to overexpressed HLA genes by negative expression correlation. In addition, the rRNA processing subnetwork contains the RPS18 gene, which is not differentially expressed, but has significant variant association. The RPS18 gene could potentially play a role in the underexpression of the genes involved in 18 S ribosomal RNA processing, which it is highly connected to. Conclusions Our analysis highlights the importance of interrogating multiple omics to enhance knowledge discovery in rare diseases. We report five subnetworks that can provide additional insights into the molecular pathogenesis of Inclusion Body Myositis. Our analytical workflow can be reused as a method to study disease mechanisms involved in other diseases when multiple omics datasets are available. |
| format | Article |
| id | doaj-art-85c60c08da9a4c8cace252ba68584c6f |
| institution | Kabale University |
| issn | 1750-1172 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj-art-85c60c08da9a4c8cace252ba68584c6f2025-01-19T12:38:27ZengBMCOrphanet Journal of Rare Diseases1750-11722025-01-0120111010.1186/s13023-024-03526-xMulti-omics analysis in inclusion body myositis identifies mir-16 responsible for HLA overexpressionDaphne Wijnbergen0Mridul Johari1Ozan Ozisik2Peter A.C. ‘t Hoen3Friederike Ehrhart4Anaïs Baudot5Chris T. Evelo6Bjarne Udd7Marco Roos8Eleni Mina9Department of Human Genetics, Leiden University Medical CenterHarry Perkins Institute of Medical Research, Centre for Medical Research, University of Western AustraliaUniversité Paris Cité, INSERM U976Department of Medical BioSciences, Radboud university medical centerDepartment of Bioinformatics - BiGCaT, NUTRIM/MHeNs, Maastricht UniversityAix Marseille University, INSERM, MMGDepartment of Bioinformatics - BiGCaT, NUTRIM, Maastricht UniversityFolkhälsen Research CenterDepartment of Human Genetics, Leiden University Medical CenterDepartment of Human Genetics, Leiden University Medical CenterAbstract Background Inclusion Body Myositis is an acquired muscle disease. Its pathogenesis is unclear due to the co-existence of inflammation, muscle degeneration and mitochondrial dysfunction. We aimed to provide a more advanced understanding of the disease by combining multi-omics analysis with prior knowledge. We applied molecular subnetwork identification to find highly interconnected subnetworks with a high degree of change in Inclusion Body Myositis. These could be used as hypotheses for potential pathomechanisms and biomarkers that are implicated in this disease. Results Our multi-omics analysis resulted in five subnetworks that exhibit changes in multiple omics layers. These subnetworks are related to antigen processing and presentation, chemokine-mediated signaling, immune response-signal transduction, rRNA processing, and mRNA splicing. An interesting finding is that the antigen processing and presentation subnetwork links the underexpressed miR-16-5p to overexpressed HLA genes by negative expression correlation. In addition, the rRNA processing subnetwork contains the RPS18 gene, which is not differentially expressed, but has significant variant association. The RPS18 gene could potentially play a role in the underexpression of the genes involved in 18 S ribosomal RNA processing, which it is highly connected to. Conclusions Our analysis highlights the importance of interrogating multiple omics to enhance knowledge discovery in rare diseases. We report five subnetworks that can provide additional insights into the molecular pathogenesis of Inclusion Body Myositis. Our analytical workflow can be reused as a method to study disease mechanisms involved in other diseases when multiple omics datasets are available.https://doi.org/10.1186/s13023-024-03526-xInclusion body myositisMulti-omicsTranscriptomicsGenomicsNetwork analysisActive subnetwork identification |
| spellingShingle | Daphne Wijnbergen Mridul Johari Ozan Ozisik Peter A.C. ‘t Hoen Friederike Ehrhart Anaïs Baudot Chris T. Evelo Bjarne Udd Marco Roos Eleni Mina Multi-omics analysis in inclusion body myositis identifies mir-16 responsible for HLA overexpression Orphanet Journal of Rare Diseases Inclusion body myositis Multi-omics Transcriptomics Genomics Network analysis Active subnetwork identification |
| title | Multi-omics analysis in inclusion body myositis identifies mir-16 responsible for HLA overexpression |
| title_full | Multi-omics analysis in inclusion body myositis identifies mir-16 responsible for HLA overexpression |
| title_fullStr | Multi-omics analysis in inclusion body myositis identifies mir-16 responsible for HLA overexpression |
| title_full_unstemmed | Multi-omics analysis in inclusion body myositis identifies mir-16 responsible for HLA overexpression |
| title_short | Multi-omics analysis in inclusion body myositis identifies mir-16 responsible for HLA overexpression |
| title_sort | multi omics analysis in inclusion body myositis identifies mir 16 responsible for hla overexpression |
| topic | Inclusion body myositis Multi-omics Transcriptomics Genomics Network analysis Active subnetwork identification |
| url | https://doi.org/10.1186/s13023-024-03526-x |
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