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Fig. 5 | Genome Medicine

Fig. 5

From: Exploring the pre-immune landscape of antigen-specific T cells

Fig. 5

Specific T cell frequencies at baseline correlate with epitope immunogenicity profiles. a Principal component analysis of epitope space for immunogenic and non-immunogenic epitopes from Chowell et al. Dimensionality reduction was performed on 10-dimensional vectors of Kidera factor sums for each epitope, and the first two principal components were used to plot each epitope into a 2D plane using the Euclidean distance between Kidera factor vectors. The density map shows the overall epitope repertoire space. Red and blue contour maps show densities for immunogenic and non-immunogenic epitopes, respectively. b Correlation of median theoretical rearrangement probabilities of TCRs specific for certain epitopes and T-scores for the Euclidean distance of each VDJdb epitope to the immunogenic and non-immunogenic epitopes computed in Kidera factor space (R = 0.35, P = 0.039). T-scores were computed by comparing distances from a given epitope to immunogenic versus non-immunogenic epitopes. Only epitopes with more than 30 associated TCRs were selected from VDJdb. c A schematic representation of the algorithm used to transform categorical representation of immunogenicity (yes/no for data from Chowell et al., and yes/unknown for VDJdb epitopes) into a continuous set of probability values using an immunogenicity classifier to enable a correlation analysis between immunogenicity and TCR repertoire structure. d Correlation of median theoretical rearrangement probabilities of TCRs specific for certain epitopes and the probability of a given epitope being immunogenic as estimated using an expectation maximization classifier (R = 0.37, P = 0.031). e Cumulative distribution function plot for median rearrangement probabilities predicted for immunogenic and non-immunogenic epitopes using a simple linear model based on Kidera factor sums. The difference in predicted values for all data from Chowell et al. is highly significant (P < 2 × 10−16, Kolmogorov–Smirnov test)

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