Multi-omic signatures of sarcoidosis and progression in bronchoalveolar lavage cells
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| Publikašuvnnas: | Respiratory Research vol. 25, no. 1 (Dec 2024), p. 289 |
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| Váldodahkki: | |
| Eará dahkkit: | , , , , , , , , , , |
| Almmustuhtton: |
Nature Publishing Group
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| Fáttát: | |
| Liŋkkat: | Citation/Abstract Full Text Full Text - PDF |
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| 022 | |a 1465-9921 | ||
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| 024 | 7 | |a 10.1186/s12931-024-02919-7 |2 doi | |
| 035 | |a 3256363231 | ||
| 045 | 2 | |b d20241201 |b d20241231 | |
| 084 | |a 58430 |2 nlm | ||
| 100 | 1 | |a Konigsberg, Iain R. |u University of Colorado - Anschutz Medical Campus, Department of Biomedical Informatics, School of Medicine, Aurora, USA (GRID:grid.430503.1) (ISNI:0000 0001 0703 675X) | |
| 245 | 1 | |a Multi-omic signatures of sarcoidosis and progression in bronchoalveolar lavage cells | |
| 260 | |b Nature Publishing Group |c Dec 2024 | ||
| 513 | |a Journal Article | ||
| 520 | 3 | |a BackgroundSarcoidosis is a heterogeneous granulomatous disease with no accurate biomarkers of disease progression. Therefore, we profiled and integrated the DNA methylome, mRNAs, and microRNAs to identify molecular changes associated with sarcoidosis and disease progression that might illuminate underlying mechanisms of disease and potential biomarkers.MethodsBronchoalveolar lavage cells from 64 sarcoidosis subjects and 16 healthy controls were used. DNA methylation was profiled on Illumina HumanMethylationEPIC arrays, mRNA by RNA-sequencing, and miRNAs by small RNA-sequencing. Linear models were fit to test for effect of sarcoidosis diagnosis and progression phenotype, adjusting for age, sex, smoking, and principal components of the data. We built a supervised multi-omics model using a subset of features from each dataset.ResultsWe identified 1,459 CpGs, 64 mRNAs, and five miRNAs associated with sarcoidosis versus controls and four mRNAs associated with disease progression. Our integrated model emphasized the prominence of the PI3K/AKT1 pathway, which is important in T cell and mTOR function. Novel immune related genes and miRNAs including LYST, RGS14, SLFN12L, and hsa-miR-199b-5p, distinguished sarcoidosis from controls. Our integrated model also demonstrated differential expression/methylation of IL20RB, ABCC11, SFSWAP, AGBL4, miR-146a-3p, and miR-378b between non-progressive and progressive sarcoidosis.ConclusionsLeveraging the DNA methylome, transcriptome, and miRNA-sequencing in sarcoidosis BAL cells, we detected widespread molecular changes associated with disease, many which are involved in immune response. These molecules may serve as diagnostic/prognostic biomarkers and/or drug targets, although future testing is required for confirmation. | |
| 653 | |a DNA methylation | ||
| 653 | |a Transcriptomes | ||
| 653 | |a Chemokines | ||
| 653 | |a Datasets | ||
| 653 | |a Immune system | ||
| 653 | |a TOR protein | ||
| 653 | |a miRNA | ||
| 653 | |a Lymphocytes T | ||
| 653 | |a Ribonucleic acid--RNA | ||
| 653 | |a Therapeutic targets | ||
| 653 | |a Phenotypes | ||
| 653 | |a MicroRNAs | ||
| 653 | |a 1-Phosphatidylinositol 3-kinase | ||
| 653 | |a Genomes | ||
| 653 | |a Lung diseases | ||
| 653 | |a Epigenetics | ||
| 653 | |a Alveoli | ||
| 653 | |a Lymphocytes | ||
| 653 | |a Lavage | ||
| 653 | |a Sarcoidosis | ||
| 653 | |a Bronchoscopy | ||
| 653 | |a Gene expression | ||
| 653 | |a Gene sequencing | ||
| 653 | |a Immune response | ||
| 653 | |a Bronchus | ||
| 653 | |a Biomarkers | ||
| 653 | |a Deoxyribonucleic acid--DNA | ||
| 653 | |a AKT1 protein | ||
| 653 | |a Social | ||
| 700 | 1 | |a Lin, Nancy W. |u National Jewish Health, Division of Environmental and Occupational Health Sciences, Department of Medicine, Denver, USA (GRID:grid.240341.0) (ISNI:0000 0004 0396 0728); University of Colorado - Anschutz Medical Campus, Division of Pulmonary and Critical Care Sciences, Department of Medicine, School of Medicine, Aurora, USA (GRID:grid.430503.1) (ISNI:0000 0001 0703 675X); Johns Hopkins University, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Baltimore, USA (GRID:grid.21107.35) (ISNI:0000 0001 2171 9311) | |
| 700 | 1 | |a Liao, Shu-Yi |u National Jewish Health, Division of Environmental and Occupational Health Sciences, Department of Medicine, Denver, USA (GRID:grid.240341.0) (ISNI:0000 0004 0396 0728); University of Colorado - Anschutz Medical Campus, Division of Pulmonary and Critical Care Sciences, Department of Medicine, School of Medicine, Aurora, USA (GRID:grid.430503.1) (ISNI:0000 0001 0703 675X); Colorado School of Public Health, Department of Environmental and Occupational Health, Aurora, USA (GRID:grid.414594.9) (ISNI:0000 0004 0401 9614) | |
| 700 | 1 | |a Liu, Cuining |u Colorado School of Public Health, Department of Biostatistics and Informatics, Aurora, USA (GRID:grid.414594.9) (ISNI:0000 0004 0401 9614) | |
| 700 | 1 | |a MacPhail, Kristyn |u National Jewish Health, Division of Environmental and Occupational Health Sciences, Department of Medicine, Denver, USA (GRID:grid.240341.0) (ISNI:0000 0004 0396 0728) | |
| 700 | 1 | |a Mroz, Margaret M. |u National Jewish Health, Division of Environmental and Occupational Health Sciences, Department of Medicine, Denver, USA (GRID:grid.240341.0) (ISNI:0000 0004 0396 0728) | |
| 700 | 1 | |a Davidson, Elizabeth |u University of Colorado - Anschutz Medical Campus, Department of Biomedical Informatics, School of Medicine, Aurora, USA (GRID:grid.430503.1) (ISNI:0000 0001 0703 675X) | |
| 700 | 1 | |a Restrepo, Clara I. |u National Jewish Health, Division of Environmental and Occupational Health Sciences, Department of Medicine, Denver, USA (GRID:grid.240341.0) (ISNI:0000 0004 0396 0728) | |
| 700 | 1 | |a Sharma, Sunita |u University of Colorado - Anschutz Medical Campus, Division of Pulmonary and Critical Care Sciences, Department of Medicine, School of Medicine, Aurora, USA (GRID:grid.430503.1) (ISNI:0000 0001 0703 675X) | |
| 700 | 1 | |a Li, Li |u National Jewish Health, Division of Environmental and Occupational Health Sciences, Department of Medicine, Denver, USA (GRID:grid.240341.0) (ISNI:0000 0004 0396 0728); University of Colorado - Anschutz Medical Campus, Division of Pulmonary and Critical Care Sciences, Department of Medicine, School of Medicine, Aurora, USA (GRID:grid.430503.1) (ISNI:0000 0001 0703 675X) | |
| 700 | 1 | |a Maier, Lisa A. |u National Jewish Health, Division of Environmental and Occupational Health Sciences, Department of Medicine, Denver, USA (GRID:grid.240341.0) (ISNI:0000 0004 0396 0728); University of Colorado - Anschutz Medical Campus, Division of Pulmonary and Critical Care Sciences, Department of Medicine, School of Medicine, Aurora, USA (GRID:grid.430503.1) (ISNI:0000 0001 0703 675X); Colorado School of Public Health, Department of Environmental and Occupational Health, Aurora, USA (GRID:grid.414594.9) (ISNI:0000 0004 0401 9614) | |
| 700 | 1 | |a Yang, Ivana V. |u University of Colorado - Anschutz Medical Campus, Department of Biomedical Informatics, School of Medicine, Aurora, USA (GRID:grid.430503.1) (ISNI:0000 0001 0703 675X); University of Colorado - Anschutz Medical Campus, Division of Pulmonary and Critical Care Sciences, Department of Medicine, School of Medicine, Aurora, USA (GRID:grid.430503.1) (ISNI:0000 0001 0703 675X) | |
| 773 | 0 | |t Respiratory Research |g vol. 25, no. 1 (Dec 2024), p. 289 | |
| 786 | 0 | |d ProQuest |t Health & Medical Collection | |
| 856 | 4 | 1 | |3 Citation/Abstract |u https://www.proquest.com/docview/3256363231/abstract/embedded/J7RWLIQ9I3C9JK51?source=fedsrch |
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| 856 | 4 | 0 | |3 Full Text - PDF |u https://www.proquest.com/docview/3256363231/fulltextPDF/embedded/J7RWLIQ9I3C9JK51?source=fedsrch |