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Ying Li

Publications and source records attributed to Ying Li.

2 recordsLinked to original sources

Using Cell line and Patient samples to improve Drug Response Prediction

BackgroundRecent 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.\n\nMethodsWe 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.\n\nResultsOur 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.\n\nConclusionsThe 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.

Bioinformatics

Successful asexual lineages of the Irish potato Famine pathogen are triploid

The oomycete Phytophthora infestans was the causal agent of the Irish Great Famine and is a recurring threat to global food security1. The pathogen can reproduce both sexually and asexually and has a potential to adapt both abiotic and biotic environment2. Although in many regions the A1 and A2 mating types coexist, the far majority of isolates belong to few clonal, asexual lineages3. As other oomycetes, P. infestans is thought to be diploid during the vegetative phase of its life cycle3, but it was observed that trisomy correlated with virulence and mating type locus4 and that polyploidy can occur in some isolates5,6. It remains unknown about the frequency of polyploidy occurrence in nature and the relationship between ploidy level and sexuality. Here we discovered that the sexuality of P. infestans isolates correlates with ploidy by comparison of microsatellite fingerprinting, genome-wide polymorphism, DNA quantity, and chromosome numbers. The sexual progeny of P. infestans in nature are diploid, whereas the asexual lineages are mostly triploids, including successful clonal lineages US-1 and 13_A2. This study reveals polyploidization as an extra evolutionary risk to this notorious plant destroyer.

Evolutionary Biology