Anatomical comparison populations and threshold transport in vascular transcriptomic classification

In GSE100927 atherosclerotic versus lesion-free donor arteries, mean held-out pooled AUROC reached 0.9968, but external AUROC dropped to 0.877, limiting transferable thresholds.

• Why it matters: High vascular transcriptomic discrimination can mask dependence on comparison populations, gene selection, and score scaling, which affects whether rankings and thresholds generalize beyond the training data.
• What they did: They trained a ridge model using sample-wise gene ranks with training-only selection of 200 genes, then decomposed AUROC across nine case–bed–control–bed comparisons and tested held-out folds plus external datasets.
• The result: External plaque/intact AUROC was 0.877 (0.792–0.947) in GSE43292 and histological AUROC was 0.986 (0.942–1.000) in GSE28829; all external probabilities were below 0.5, and source-derived thresholds yielded zero external sensitivity.

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