Using cell line and patient samples to improve predictions of patient drug response
Bibliographic record
Abstract
Abstract Background Recent advances in high-throughput technologies have facilitated the profiling of large panels of cancer cell lines with responses measured for thousands of drugs. The computational challenge is now to realize the potential of these data in predicting patients’ responses to these drugs in the clinic. Methods We address this issue by examining the spectrum of prediction models of patient response: models predicting directly from cell lines, those predicting directly from patients, and those trained on cell lines and patients at the same time. We tested 21 classification models on four drugs, that are bortezomib, erlotinib, docetaxel and epirubicin, for which clinical trial data were available. Results Our integrative models consistently outperform cell line-based predictors, indicating that there are limitations to the predictive potential of in vitro data alone. Furthermore, these integrative models achieve better predictive accuracy and require substantially fewer patients than would be the case if only patient data were available. Conclusions The integration of in vitro and ex vivo genomic data results in more accurate predictors using only a fraction of the patient information, which can help optimize the development of personalized predictors of therapy response. Altogether our results support the relevance of preclinical data for therapy prediction in clinical trials, enabling more efficient and cost-effective trial design.
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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 | 0.003 | 0.005 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".