Wednesday, November 17, 2021

CCMB Seminar: "Mechanistic modeling of immune cell activation in cancer"

4:00 PM

Forum Hall, 4th Floor, Palmer Commons Building

CCMB Seminar Series – sponsored by DCMB
by Craig Galban (U-M)

Background

Chronic obstructive pulmonary disease (COPD) presents significant clinical heterogeneity and a wide variety of progression trajectories [1]. Clinical trajectory analysis (ClinTrajAn) is a powerful tool based on elastic principal graphs for the calculation of trajectories from large cross-sectional clinical data sets [2].

Aims and objectives

Our objective was to determine potential risk-factors by evaluate progression trajectories in COPD using ClinTrajAn on the COPDGene Phase I (baseline visit) dataset.

Methods

7883 participants, current and former smokers with GOLD 0 thru 4 COPD, from Phase I of the COPDGene study, were utilized for this work. 55 features were obtained for each subject, including demographics, spirometry, smoking history and computed tomography (CT), which included Parametric Response Mapping (PRM). Developed by our group, PRM is capable of simultaneously measuring small airways disease and emphysema which are the main contributors of airflow limitations in COPD. The resulting data matrix was analyzed with ClinTrajAn.

Results

A principal tree, with 13 branch segments and 8 termini, was generated (Figure 1). There was a clearly recognized trajectory from healthier subjects through decreasing lung function and increasing age (Figure 1 A), increasing in GOLD (Figure 1 B), to an emphysema high terminus (Figure 1 C). Notably this method illustrated numerous branching points along this trajectory.

Conclusions

In this study we used ClinTrajAn to obtain a map of disease progression trajectories in COPD including clinically recognized pathogenesis. Our next steps will be to further validate this approach using longitudinal data from the COPDGene follow-up visits.