Assessment of Modeling Strategies for Drug Response Prediction in Cell Lines and Xenografts

Written By Roman Kurilov
Assessment of Modeling Strategies for Drug Response Prediction in Cell Lines and Xenografts
  • Publsiher : Unknown
  • Release : 01 January 1970
  • ISBN :
  • Pages : pages
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Download or read book entitled Assessment of Modeling Strategies for Drug Response Prediction in Cell Lines and Xenografts by author: Roman Kurilov which was release on 01 January 1970 and published by Unknown with total page pages . This book available in PDF, EPUB and Kindle Format. Abstract: Despite significant progress in cancer research, effective cancer treatment is still a challenge. Cancer treatment approaches are shifting from standard cytotoxic chemotherapy regimens towards a precision oncology paradigm, where a choice of treatment is personalized, i.e. based on a tumor's molecular features. In order to match tumor molecular features with therapeutics we need to identify biomarkers of response and build predictive models. Recent growth of large-scale pharmacogenomics resources which combine drug sensitivity and multi-omics information on a large number of samples provides necessary data for biomarker identification and drug response modelling. However, although many efforts of using this information for drug response prediction have been made, our ability to accurately predict drug response using genetic data remains limited. In this work we used pharmacogenomics data from the largest publicly available studies in order to systematically assess various aspects of the drug response model-building process with the ultimate goal of improving prediction accuracy. We applied several machine learning methods (regularized regression, support vector machines, random forest) for predicting response to a number of drugs. We found that while accuracy of response prediction varies across drugs (in most of the cases R2 values vary between 0.1 and 0.3), different machine learning algorithms applied for the the same drug have similar prediction performance. Experiments with a range of different training sets for the same drug showed that predictive power of a model depends on the type of molecular data, the selected drug response metric, and the size of the training set. It depends less on number of features selected for modelling and on class imbalance in training set. We also implemented and tested two methods for improving consistency for pharmacogenomics data coming from different datasets. We tested our ability to correctly predict response in xenografts and patients using models trained on cell lines. Only in a fraction of the tested cases we managed to get reasonably accurate predictions, particularly in case of response to erlotinib in the NSCLC xenograft cohort, and in cases of responses to erlotinib and docetaxel in the NSCLC and BRCA patient cohorts respectively. This work also includes two applied pharmacogenomics analyses. The first is an analysis of a drug-sensitivity screen performed on a panel of Burkitt cell lines. This combines unsupervised data exploration with supervised modelling. The second is an analysis of drug-sensitivity data for the DKFZ-608 compound and the generation of the corresponding response prediction model. In summary, we applied machine learning techniques to available high-throughput pharmacogenomics data to study the determinants of accurate drug response prediction. Our results can help to draft guidelines for building accurate models for personalized drug response prediction and therefore contribute to advancing of precision oncology.

Assessment of Modeling Strategies for Drug Response Prediction in Cell Lines and Xenografts

Assessment of Modeling Strategies for Drug Response Prediction in Cell Lines and Xenografts
  • Author : Roman Kurilov
  • Publisher : Unknown
  • Release Date : 2019*
  • Total pages : 212
  • ISBN :
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Summary : Abstract: Despite significant progress in cancer research, effective cancer treatment is still a challenge. Cancer treatment approaches are shifting from standard cytotoxic chemotherapy regimens towards a precision oncology paradigm, where a choice of treatment is personalized, i.e. based on a tumor's molecular features. In order to match tumor molecular ...

Journal of the National Cancer Institute

Journal of the National Cancer Institute
  • Author : Anonim
  • Publisher : Unknown
  • Release Date : 1990
  • Total pages : 212
  • ISBN :
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Summary : Read online Journal of the National Cancer Institute written by , published by which was released on 1990. Download full Journal of the National Cancer Institute Books now! Available in PDF, ePub and Kindle....

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  • Publisher : Springer Nature
  • Release Date : 2021-04-18
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  • ISBN :
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Summary : Read online Bio Nanomedicine for Cancer Therapy written by Flavia Fontana, published by Springer Nature which was released on . Download full Bio Nanomedicine for Cancer Therapy Books now! Available in PDF, ePub and Kindle....

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  • Publisher : Unknown
  • Release Date : 1983
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Summary : Read online Cumulated Index Medicus written by , published by which was released on 1983. Download full Cumulated Index Medicus Books now! Available in PDF, ePub and Kindle....

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  • Author : Thomas G. P. Grünewald,Simone Fulda
  • Publisher : Frontiers Media SA
  • Release Date : 2016-04-05
  • Total pages : 212
  • ISBN :
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Summary : Recent advances in the understanding of the biological basis of pediatric soft-tissue and bone tumors, especially owing to the advent of “omics” technologies, have led to an exponential increase in the current knowledge on the genetic and cellular patho-mechanisms that drive these diseases. This offers the unprecedented opportunity to develop ...

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  • Publisher : MDPI
  • Release Date : 2020-04-22
  • Total pages : 500
  • ISBN :
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Summary : Renal cancer is a health problem of major concern worldwide. Although tyrosine kinase inhibitors and immune check-point blockade treatments, alone or in combination, are giving promising results, failures are quite frequent due to intratumor heterogeneity and to the acquisition of drug resistance. The spectrum of renal cell carcinoma subtypes is ...

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  • Publisher : McGraw Hill Professional
  • Release Date : 2012-10-09
  • Total pages : 288
  • ISBN :
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Summary : Pharmacogenomics is comprehensive textbook detailing how genetic makeup affects a body's response to drugs....

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Summary : Read online Genetic Engineering Biotechnology News written by , published by which was released on 2008. Download full Genetic Engineering Biotechnology News Books now! Available in PDF, ePub and Kindle....

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Summary : Read online Cancer Research written by , published by which was released on 2009-12. Download full Cancer Research Books now! Available in PDF, ePub and Kindle....

Index to Theses with Abstracts Accepted for Higher Degrees by the Universities of Great Britain and Ireland and the Council for National Academic Awards

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  • Author : Anonim
  • Publisher : Unknown
  • Release Date : 2008
  • Total pages : 212
  • ISBN :
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Summary : Read online Index to Theses with Abstracts Accepted for Higher Degrees by the Universities of Great Britain and Ireland and the Council for National Academic Awards written by , published by which was released on 2008. Download full Index to Theses with Abstracts Accepted for Higher Degrees by the Universities of Great ...

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  • Author : John Bodenhan Taylor,Jake Plattner,D. J. Triggle,Manoj C Desai
  • Publisher : Elsevier Science Limited
  • Release Date : 2007
  • Total pages : 1060
  • ISBN :
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Summary : This volume reviews important therapeutic areas, their causes, diagnosis, experimental disease models, treatments, unmet medical needs and future research areas. Areas covered include Cancer (biology, chemotherapy, mechanism & target approaches), Infectious Diseases (viral [herpes, HIV], fungal, bacterial & parasitic), Inflammation & Immunology (arthritis, asthma) and Dermatology (acne, psoriasis). For each area experts examine ...

Proceedings of the American Association for Cancer Research

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  • Author : American Association for Cancer Research. Meeting,American Association for Cancer Research
  • Publisher : Unknown
  • Release Date : 2001
  • Total pages : 212
  • ISBN :
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Summary : Contains abstracts of the scientific proceedings of the 73rd- annual meetings of the American Association for Cancer Research (1982- )....

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  • Author : American Association for Cancer Research
  • Publisher : Unknown
  • Release Date : 1988
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Summary : Contains abstracts of the scientific proceedings of the 73rd- annual meetings of the American Association for Cancer Research (1982- )....

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  • Author : Anonim
  • Publisher : ScholarlyEditions
  • Release Date : 2012-01-09
  • Total pages : 4229
  • ISBN :
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Summary : Issues in Pharmacology, Pharmacy, Drug Research, and Drug Innovation: 2011 Edition is a ScholarlyEditions™ eBook that delivers timely, authoritative, and comprehensive information about Pharmacology, Pharmacy, Drug Research, and Drug Innovation. The editors have built Issues in Pharmacology, Pharmacy, Drug Research, and Drug Innovation: 2011 Edition on the vast information databases of ScholarlyNews.™ ...

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  • Author : Anonim
  • Publisher : Unknown
  • Release Date : 1998
  • Total pages : 212
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Summary : Read online Dissertation Abstracts International written by , published by which was released on 1998. Download full Dissertation Abstracts International Books now! Available in PDF, ePub and Kindle....