BioCOMPASS: Integrating Biomarkers into Transformer-Based Immunotherapy Response Prediction

arXiv cs.LG / 4/2/2026

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Key Points

  • The paper addresses a key limitation in immunotherapy response prediction: small and heterogeneous datasets lead to models that often perform worse on unseen patient cohorts, cancers, treatments, or sequencing protocols.
  • It introduces BioCOMPASS, an extension of the COMPASS transformer-based model that improves generalization by integrating biomarker and treatment information through additional loss components rather than direct biomarker inputs.
  • The authors use alignment between biomarkers/treatment signals and the model’s intermediate representations, including techniques such as treatment gating and pathway consistency loss.
  • Experiments using Leave-one-cohort-out, Leave-one-cancer-type-out, and Leave-one-treatment-out evaluation strategies show that these components meaningfully improve generalization performance.
  • The study concludes that carefully designed objectives that leverage clinical/domain knowledge can be a promising direction to strengthen transformer-based immunotherapy prediction models.

Abstract

Datasets used in immunotherapy response prediction are typically small in size, as well as diverse in cancer type, drug administered, and sequencer used. Models often drop in performance when tested on patient cohorts that are not included in the training process. Recent work has shown that transformer-based models along with self-supervised learning show better generalisation performance than threshold-based biomarkers, but is still suboptimal. We present BioCOMPASS, an extension of a transformer-based model called COMPASS, that integrates biomarkers and treatment information to further improve its generalisability. Instead of feeding biomarker data as input, we built loss components to align them with the model's intermediate representations. We found that components such as treatment gating and pathway consistency loss improved generalisability when evaluated with Leave-one-cohort-out, Leave-one-cancer-type-out and Leave-one-treatment-out strategies. Results show that building components that exploit biomarker and treatment information can help in generalisability of immunotherapy response prediction. Careful curation of additional components that leverage complementary clinical information and domain knowledge represents a promising direction for future research.