TRACER: response-protected cross-domain alignment of cancer pharmacogenomic models with patient tumors.
- 1College of Computer Science and Artificial Intelligence, Northeast Forestry University, No. 26 Hexing Road, Xiangfang District, Harbin, Heilongjiang 150040, China.
- 2Department of Computer Science and Technology, Faculty of Computing, Harbin Institute of Technology, No. 92 West Dazhi Street, Nangang District, Harbin, Heilongjiang 150001, China.
Abstract
Pharmacogenomics integrates tumor molecular features with drug responses to support precision oncology, but biological domain shifts and optimization conflicts hinder transfer from screened cell lines to unlabeled patient tumors. We developed TRACER (Transfer of Response Across domains via Conflict-aware End-to-end Regulation), an end-to-end framework combining supervised drug-response prediction, biologically conditioned neighbor alignment and response-protected gradient regulation. By projecting only conflicting components of the auxiliary alignment gradient, TRACER preserves the response-optimization direction learned from experimental labels. Across ModelID-disjoint, seen-drug splits, TRACER-Full achieved a global Pearson correlation of 0.5125 $\pm $ 0.0192 on per-drug z-standardized test pairs, compared with 0.5179 $\pm $ 0.0193 for Response-only, a mean difference of −0.0054. Mean oncogenic Hallmark neighbor consistency increased by 0.1162 ± 0.0210 in alignment-excluded The Cancer Genome Atlas audit samples. At the patient level, a source-validation-defined drug partition and uniform stability analysis supported four predicted pharmacological response subtypes (PRSs) in breast invasive carcinoma (BRCA), four in uterine corpus endometrial carcinoma (UCEC) and two in sarcoma (SARC). PRS-construction-excluded drugs characterized distinct predicted mechanism-level profiles, and pan-cancer indication recovery provided a lineage-aware internal consistency assessment of the patient rankings. TRACER provides an interpretable and auditable framework for response-preserving cross-domain alignment and it generates patient pharmacogenomic hypotheses for subsequent functional validation.
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BibTeX
@article{wang2026tracer,
title = {{TRACER: response-protected cross-domain alignment of cancer pharmacogenomic models with patient tumors.}},
author = {Zhenxing Wang and Qihe Wang and Guangchao Wang and Guohua Wang and Yuming Zhao},
journal = {Briefings in bioinformatics},
year = {2026},
month = sep,
doi = {10.1093/bib/bbag593},
url = {https://europepmc.org/article/MED/42949538},
note = {CC BY},
}
RIS
TY - JOUR
TI - TRACER: response-protected cross-domain alignment of cancer pharmacogenomic models with patient tumors.
AU - Zhenxing Wang
AU - Qihe Wang
AU - Guangchao Wang
AU - Guohua Wang
AU - Yuming Zhao
PY - 2026
DA - 2026/09/01
JO - Briefings in bioinformatics
DO - 10.1093/bib/bbag593
UR - https://europepmc.org/article/MED/42949538
AB - Pharmacogenomics integrates tumor molecular features with drug responses to support precision oncology, but biological domain shifts and optimization conflicts hinder transfer from screened cell lines to unlabeled patient tumors. We developed TRACER (Transfer of Response Across domains via Conflict-aware End-to-end Regulation), an end-to-end framework combining supervised drug-response prediction, biologically conditioned neighbor alignment and response-protected gradient regulation. By projecting only conflicting components of the auxiliary alignment gradient, TRACER preserves the response-optimization direction learned from experimental labels. Across ModelID-disjoint, seen-drug splits, TRACER-Full achieved a global Pearson correlation of 0.5125 $\pm $ 0.0192 on per-drug z-standardized test pairs, compared with 0.5179 $\pm $ 0.0193 for Response-only, a mean difference of −0.0054. Mean oncogenic Hallmark neighbor consistency increased by 0.1162 ± 0.0210 in alignment-excluded The Cancer Genome Atlas audit samples. At the patient level, a source-validation-defined drug partition and uniform stability analysis supported four predicted pharmacological response subtypes (PRSs) in breast invasive carcinoma (BRCA), four in uterine corpus endometrial carcinoma (UCEC) and two in sarcoma (SARC). PRS-construction-excluded drugs characterized distinct predicted mechanism-level profiles, and pan-cancer indication recovery provided a lineage-aware internal consistency assessment of the patient rankings. TRACER provides an interpretable and auditable framework for response-preserving cross-domain alignment and it generates patient pharmacogenomic hypotheses for subsequent functional validation.
SN - 1467-5463
SN - 1477-4054
ER -