지원사업
학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
커뮤니티
연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2019.1
- 수록면
- 672 - 684 (13page)
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초록· 키워드
오류제보하기
Purpose This study was conducted to develop and validate an individualized prediction model for automated detection of acquired taxane resistance (ATR). Materials and Methods Penalized regression, combined with an individualized pathway score algorithm, was applied to construct a predictive model using publically available genomic cohorts of ATR and intrinsic taxane resistance (ITR). To develop a model with enhanced generalizability, we merged multiple ATR studies then updated the learning parameter via robust cross-study validation. Results For internal cross-study validation, the ATR model produced a perfect performance with an overall area under the receiver operating curve (AUROC) of 1.000 with an area under the precision-recall curve (AUPRC) of 1.000, a Brier score of 0.007, a sensitivity and a specificity of 100%. The model showed an excellent performance on two independent blind ATR cohorts (overall AUROC of 0.940, AUPRC of 0.940, a Brier score of 0.127). When we applied our algorithm to two large-scale pharmacogenomic resources for ITR, the Cancer Genome Project (CGP) and the Cancer Cell Line Encyclopedia (CCLE), an overall ITR cross-study AUROC was 0.70, which is a far better accuracy than an almost random level reported by previous studies. Furthermore, this model had a high transferability on blind ATR cohorts with an AUROC of 0.69, suggesting that general predictive features may be at work across both ITR and ATR. Conclusion We successfully constructed a multi-study–derived personalized prediction model for ATR with excellent accuracy, generalizability, and transferability.
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참고문헌 (26)
참고문헌 신청
Nussbaumer S / 2011 / Analysis of anticancer drugs : a review / Talanta 85:2265~2289
Haibe-Kains B / 2013 / Inconsistency in large pharmacogenomic studies / Nature 504:389~393
Bouhaddou M / 2016 / Drug response consistency in CCLE and CGP / Nature 540:E9~E10
Domingo-Domenech J / 2012 / Suppression of acquired docetaxel resistance in prostate cancer through depletion of notch- and hedgehog-dependent tumorinitiating cells / Cancer Cell 22:373~388
Zwart A / Gene expression data of sensitive, Docetaxel resistant and paclitaxel resistant MDA-MB-231 cells. GEO DataSets. Series GSE28784
Haibe-Kains B / 2013 / Inconsistency in large pharmacogenomic studies / Nature 504:389~393
Bouhaddou M / 2016 / Drug response consistency in CCLE and CGP / Nature 540:E9~E10
Domingo-Domenech J / 2012 / Suppression of acquired docetaxel resistance in prostate cancer through depletion of notch- and hedgehog-dependent tumorinitiating cells / Cancer Cell 22:373~388
Zwart A / Gene expression data of sensitive, Docetaxel resistant and paclitaxel resistant MDA-MB-231 cells. GEO DataSets. Series GSE28784
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