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Clonal Tracking & AUC Kinetics

TCR Repertoire Analysis — Notebook 05: Longitudinal clonotype trajectories, time-integrated exposure, and persistence analysis
Joshua LuthyR + edgeR + tidyverseSynthetic Data2025
Contents
  1. Analysis Overview
  2. Clonal Trajectories
  3. AUC Analysis
  4. Persistence Analysis
  5. Summary

01 Analysis Overview

This notebook tracks individual clonotype kinetics across longitudinal post-infusion timepoints (Wk2, Wk4, Wk8, Wk12). We characterize expansion kinetics, peak timing, persistence, and compute AUC (area under the curve) as a time-integrated clonal exposure metric.

6
Timepoints
120
Product Clones Tracked
2.0
Mean AUC (CR)
0.2
Mean AUC (PD)

02 Clonal Trajectories

We plot the frequency trajectory of the top 5 Product clonotypes per patient across all timepoints, from Apheresis through 12 weeks post-infusion.

Figure 1. Top 5 Product clonotype trajectories for CR patients (PT-001, PT-002). Clones expand dramatically post-infusion, peaking at Wk4–Wk8, with sustained persistence through Wk12.
Observation

CR patients show dramatic post-infusion expansion of their top Product clones, with frequencies peaking at Wk4–Wk8 and sustained persistence through Wk12. PD patients show weaker, more transient expansion with rapid decline.

03 AUC Analysis

AUC provides a single summary metric for time-integrated clonal exposure, computed via trapezoidal integration over the post-infusion timepoints.

# Trapezoidal AUC computation auc <- 0 for (i in 1:(length(timepoints) - 1)) { dt <- weeks[i+1] - weeks[i] auc <- auc + 0.5 * (freq[i] + freq[i+1]) * dt }
Figure 2. Clonal AUC by clinical response. CR patients show significantly higher time-integrated clonal exposure than PD patients.

04 Persistence Analysis

Persistence ratio = frequency at Wk12 / peak frequency. A ratio of 1.0 means the clone maintained its peak; lower values indicate decline.

Figure 3. Clonal persistence ratio by clinical response. CR patients retain 60–90% of peak frequency at Wk12, while PD patients decline to <30%.
0.82
Mean Persistence (CR)
0.31
Mean Persistence (PR)
0.09
Mean Persistence (PD)

05 Summary

Key Findings

1. CR patients show the strongest and most sustained clonal expansion, with top clones peaking at Wk4–Wk8.

2. AUC is significantly higher in CR vs PD patients — time-integrated exposure associates with clinical benefit.

3. Persistence ratios stratify by response: CR clones retain 60–90% of peak while PD clones decline to <30%.

4. Peak timing differs: CR clones peak later (Wk4–Wk8) while PD clones peak earlier and transiently (Wk2).