Radiomultiomics: quantitative CT clusters of severe asthma associated with multiomics

Area of Science:

• Pulmonary Medicine
• Radiology
• Genomics

Background:

• Severe asthma exhibits distinct quantitative computed tomography (qCT) clusters, but their replication and underlying mechanisms remain unclear.
• This study aimed to identify and validate qCT clusters in severe asthma and explore their molecular associations.

Purpose of the Study:

• To replicate previously identified qCT clusters of severe asthma in an independent cohort.
• To investigate the molecular pathways associated with these qCT-defined asthma clusters using a radiomultiomics approach.

Main Methods:

• Consensus clustering was applied to qCT measurements from the U-BIOPRED severe asthma cohort (n=105).
• Replication of clusters was performed in the ATLANTIS asthma cohort (n=97).
• Integrated enrichment analysis combined transcriptomics and proteomics data from various biological samples to characterize radiomultiomics-associated clusters (RACs).

Main Results:

• qCT clusters identified in U-BIOPRED were successfully replicated in the ATLANTIS cohort.
• Three distinct RACs were characterized: RAC1 (complement pathway), RAC2 (proliferative and semaphorin pathways), and RAC3 (cytokine, interleukin, and matrix metallopeptidase pathways).
• Each RAC exhibited unique clinical features, including BMI, lung volumes, airflow limitation, and airway wall thickness.

Conclusions:

• Severe asthma qCT clusters are replicable and associated with specific molecular pathways.
• Radiomultiomics, integrating imaging and multiomics data, presents a promising strategy for discovering novel asthma pathobiology insights.