Methods

Subjects

  • The cohort was drawn from the Idiopathic Pulmonary Fibrosis Prospective Outcomes (IPF-PRO) Registry, a multicenter US registry that enrolled patients with IPF that was diagnosed or confirmed at the enrolling center in the past 6 months.2
  • These analyses were based on samples taken at enrollment from 272 subjects who had whole blood mRNA and plasma microRNA sequencing data that met quality control filters.

Analyses

  • T-tests were used to determine differential mRNA and microRNA expression between subjects with FVC % predicted in the lowest tertile (<63.7% predicted; n=90) and the highest tertile (>76.8% predicted; n=92).
  • We then used Pearson correlation to identify negatively correlated mRNAmicroRNA pairs among:
    • mRNA transcripts with an absolute fold change >1 and p≤0.05 for the difference between lowest versus highest tertiles of FVC % predicted.
    • microRNAs with p≤0.05 for the difference between lowest versus highest tertiles of FVC % predicted.
  • Functional and network analyses were used to visualize top mRNA-microRNA connections.
  • mRNA-microRNA interaction analyses were performed in R using miRComb;3 p-values were adjusted for multiple testing.
  • Pathways analysis was performed using Ingenuity Pathway Analysis (QIAGEN Inc.). Databases searched were miRTarbase, microCOSM, mirDB, targetScan, and mirWalk2.
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