Transcriptomics

Dataset Information

0

Longitudinal Blood Transcriptomic Changes Predict Lung Function Decline in Idiopathic Pulmonary Fibrosis


ABSTRACT: The Rationale: Molecular markers of disease activity that are predictive of forced vital capacity (FVC) progression in idiopathic pulmonary fibrosis are needed. Objectives: Develop a predictor using longitudinal within-patient gene expression differences (ΔGE) in peripheral blood mononuclear cells (PBMC) to predict of FVC progression. Methods: Patients in the training cohort (n=74) experiencing ≥10% relative reduction in FVC% of predicted over 12 months were categorized as progressors in contrast to the remaining stable patients. Baseline to 4-month within-patient ΔGE were correlated with FVC status. FVC-predictor genes were prioritized by two-group comparison with FDR<5%, logistic LASSO regression with p<0.05, and 10-Fold Cross-Validation with ≥50% support. Receiver operating characteristic with area under the curve (AUC) analyses were conducted in training subsets and independent validation cohorts from UChicago (n=27), UPMC (n=35), and Imperial (n=24) where different transcriptome assay platforms and varying transcriptome sampling times were used to derive ΔGE. Results: Intra-subject Compared to cross-sectional analysis of baseline GE, our longitudinal ΔGE variation approach demonstratedlargely reduced within-group sample variation and increased statistic power fin progressor and stable groups for prediction model development. A 25-gene FVC-predictor separated “progressors” from “stable” by Principal Component Analysis in the training and subsets of the training cohort. The resulting FVC-predictor consistently demonstrated high discriminatory performance independent of transcriptome assay platforms and varying sampling times in validation cohorts (AUC= 0.77-0.80). TGF beta was the highest-ranking canonical pathway by Gene Set Enrichment Analysis. Conclusions: Our novel short-term longitudinal within-patient ΔGE approach identified a FVC-predictor which may reflect disease activity and prove to be a reliable biomarker predictive of future FVC decline.

ORGANISM(S): Homo sapiens

PROVIDER: GSE132607 | GEO | 2019/09/30

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2019-09-30 | GSE133298 | GEO
2016-07-20 | E-GEOD-57387 | biostudies-arrayexpress
2005-01-09 | E-UMCU-11 | biostudies-arrayexpress
2015-04-15 | E-GEOD-46222 | biostudies-arrayexpress
2016-10-31 | GSE73582 | GEO
2016-10-31 | GSE73581 | GEO
2019-10-24 | GSE104431 | GEO
2019-10-24 | GSE104430 | GEO
2019-10-24 | GSE104429 | GEO
2015-04-15 | GSE46222 | GEO