Gene expression based inference of cancer drug sensitivity
Bibliographic record
Abstract
Inter and intra-tumoral heterogeneity are major stumbling blocks in the treatment of cancer and are responsible for imparting differential drug responses in cancer patients. Recently, the availability of high-throughput screening datasets has paved the way for machine learning based personalized therapy recommendations using the molecular profiles of cancer specimens. In this study, we introduce Precily, a predictive modeling approach to infer treatment response in cancers using gene expression data. In this context, we demonstrate the benefits of considering pathway activity estimates in tandem with drug descriptors as features. We apply Precily on single-cell and bulk RNA sequencing data associated with hundreds of cancer cell lines. We then assess the predictability of treatment outcomes using our in-house prostate cancer cell line and xenografts datasets exposed to differential treatment conditions. Further, we demonstrate the applicability of our approach on patient drug response data from The Cancer Genome Atlas and an independent clinical study describing the treatment journey of three melanoma patients. Our findings highlight the importance of chemo-transcriptomics approaches in cancer treatment selection.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".