Next-Generation Sequencing in Pulmonary Fibrosis: Translational Promise and Current Clinical Limitations

Area of Science:

• Pulmonary Medicine
• Genomics
• Molecular Biology

Background:

• Pulmonary fibrosis (PF), especially idiopathic pulmonary fibrosis (IPF), is a heterogeneous lung disease with complex genetic underpinnings.
• Current diagnostic methods struggle to capture the full biological diversity of PF.
• Next-generation sequencing (NGS) offers advanced tools for deeper disease understanding.

Purpose of the Study:

• To explore how next-generation sequencing (NGS) enhances the understanding of pulmonary fibrosis (PF) pathogenesis.
• To highlight the role of NGS in identifying genetic determinants and molecular pathways in PF.
• To assess the potential of NGS in improving diagnosis, prognosis, and patient stratification for PF.

Main Methods:

• Utilized whole-exome sequencing (WES), whole-genome sequencing (WGS), and RNA sequencing (RNA-seq) for genomic and transcriptomic profiling.
• Analyzed genetic variants in genes such as TERT, TERC, RTEL1, SFTPC, SFTPA2, and MUC5B.
• Investigated dysregulated molecular pathways including TGF-β, Wnt/β-catenin, and PI3K/Akt signalling.

Main Results:

• Identified key genetic mutations and common variants contributing to PF pathogenesis.
• Discovered polygenic risk models and clarified the genetic heterogeneity of PF.
• Revealed dysregulated signaling pathways and identified potential biomarkers for prognosis and treatment response.

Conclusions:

• NGS significantly advances the understanding of PF by uncovering genetic and molecular drivers.
• NGS technologies show promise for improved diagnostic accuracy, patient stratification, and personalized medicine in PF.
• Emerging applications like liquid biopsy and AI integration will further expand the clinical utility of NGS in managing PF.