التفاصيل البيبلوغرافية
| العنوان: |
Blood transcriptomic signature in type-2 biomarker low severe asthma and asthma control. |
| المؤلفون: |
Xue Zeng, Jing Qing, Chi-Ming Li, Jiamiao Lu, Tracy Yamawaki, Yi-Hsiang Hsu, Bryan Vander Lugt, Hailing Hsu, John Busby, PJ McDowell, David J Jackson, Ratko Djukanovic, John G Matthews, Joseph R Arron, Peter Bradding, Christopher E Brightling, Rekha Chaudhuri, David F Choy, D Cowan, SJ Fowler, Timothy C Hardman, Tim Harrison, Peter Howarth, James Lordan, AH Mansur, Andrew Menzies-Gow, Ian D Pavord, Samantha Walker, Ashley Woodcock, Liam G Heaney, investigators for the UK MRC Refractory Asthma Stratification Program |
| سنة النشر: |
2023 |
| المجموعة: |
University of Leicester: Figshare |
| مصطلحات موضوعية: |
Uncategorized, investigators for the UK MRC Refractory Asthma Stratification Program (RASP-UK) |
| الوصف: |
Background Patients with Type-2 (T2) cytokine-low severe asthma often have persistent symptoms despite suppression of T2-inflammation with corticosteroids (CS). Objectives To analyze whole blood transcriptome from 738 samples in T2-biomarker high/low severe asthma patients to relate transcriptomic signatures to T2-biomarkers and asthma symptom scores. Methods Bulk RNAseq data were generated for blood samples (baseline, Week24, Week48) from 301 participants recruited to a randomized clinical trial of CS optimization in severe asthma. Unsupervised clustering, differential gene expression analysis, and pathway analysis were performed. Patients were grouped by T2-biomarker status and symptoms. Associations between clinical characteristics and differentially expressed genes (DEGs) associated with biomarker and symptom levels were investigated. Results Unsupervised clustering identified two clusters; Cluster 2 patients were blood eosinophil low/symptom high and more likely to be receiving oral CS (OCS). Differential gene expression analysis of these clusters, with and without stratification for OCS, identified 2,960 and 4,162 DEGs respectively. 627/2,960 genes remained after adjusting for OCS by subtracting OCS signature genes. Pathway analysis identified dolichyl-diphosphooligosaccharide biosynthesis and assembly of RNA polymerase I complex as significantly enriched pathways. No stable DEGs were associated with high symptoms in T2-biomarker low patients, but numerous associated with elevated T2-biomarkers, including 15 that were up-regulated at all time-points irrespective of symptom level. Conclusions OCS have a considerable effect on whole blood transcriptome. DEG analysis demonstrates a clear T2-biomarker transcriptomic signature, but no signature was found in association with T2-biomarker low patients, including those with a high symptom burden. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
unknown |
| العلاقة: |
2381/23600112.v1; https://figshare.com/articles/journal_contribution/Blood_transcriptomic_signature_in_type-2_biomarker_low_severe_asthma_and_asthma_control_/23600112Test |
| الإتاحة: |
https://figshare.com/articles/journal_contribution/Blood_transcriptomic_signature_in_type-2_biomarker_low_severe_asthma_and_asthma_control_/23600112Test |
| حقوق: |
CC BY 4.0 |
| رقم الانضمام: |
edsbas.A38B80A9 |
| قاعدة البيانات: |
BASE |
