Transcriptomic similarity guides source selection beyond tissue lineage
- 1Institute of Clinical Medical Sciences, China-Japan Friendship Hospital
Abstract
Perturbational and pharmacogenomic maps remain incomplete across cellular contexts, leaving a practical source-selection question before response prediction: which measured context should inform an unmeasured target? We tested whether baseline transcriptomic similarity ranks candidate sources for held-out targets, separating source ranking from aggregation and transfer-uncertainty decisions. Similarity tracked matched-response concordance in LINCS and GSE306429; selected-source utility exceeded random expectation in GSE306429 ({Delta}U = 0.034; P = 0.002) and in exact-time-matched MIX-Seq tasks ({Delta}U = 0.046). In the full GDSC2 analysis, the drug-balanced ranking effect was 0.359 (95% CI, 0.337-0.383). In a lineage-restricted analysis of the same eligible subset, within-tissue ranking remained positive at 0.130 (95% CI, 0.119-0.141), retaining 35.8% of the same-subset global effect (0.363; 95% CI, 0.342-0.386). Global transcriptomic top-1 selection exceeded tissue-matched random selection by 0.154 (95% CI, 0.143-0.164). Thus, baseline similarity adds source-ranking information after tissue matching in the evaluated setting, while ranking alone does not resolve whether to aggregate sources or how to quantify transfer uncertainty.
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BibTeX
@misc{jiang2026transcriptomic,
title = {{Transcriptomic similarity guides source selection beyond tissue lineage}},
author = {L. Jiang and J. Pang and B. Luo and X. Wu and X. Li and H. Zhang},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.26.761823},
url = {https://www.biorxiv.org/content/10.64898/2026.10.26.761823v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Transcriptomic similarity guides source selection beyond tissue lineage
AU - L. Jiang
AU - J. Pang
AU - B. Luo
AU - X. Wu
AU - X. Li
AU - H. Zhang
PY - 2026
DA - 2026/10/26
PB - bioRxiv
DO - 10.64898/2026.10.26.761823
UR - https://www.biorxiv.org/content/10.64898/2026.10.26.761823v1
AB - Perturbational and pharmacogenomic maps remain incomplete across cellular contexts, leaving a practical source-selection question before response prediction: which measured context should inform an unmeasured target? We tested whether baseline transcriptomic similarity ranks candidate sources for held-out targets, separating source ranking from aggregation and transfer-uncertainty decisions. Similarity tracked matched-response concordance in LINCS and GSE306429; selected-source utility exceeded random expectation in GSE306429 ({Delta}U = 0.034; P = 0.002) and in exact-time-matched MIX-Seq tasks ({Delta}U = 0.046). In the full GDSC2 analysis, the drug-balanced ranking effect was 0.359 (95% CI, 0.337-0.383). In a lineage-restricted analysis of the same eligible subset, within-tissue ranking remained positive at 0.130 (95% CI, 0.119-0.141), retaining 35.8% of the same-subset global effect (0.363; 95% CI, 0.342-0.386). Global transcriptomic top-1 selection exceeded tissue-matched random selection by 0.154 (95% CI, 0.143-0.164). Thus, baseline similarity adds source-ranking information after tissue matching in the evaluated setting, while ranking alone does not resolve whether to aggregate sources or how to quantify transfer uncertainty.
ER -