Establishing predictive machine learning models for drug responses in patient derived cell culture.

Journal: NPJ precision oncology
Published Date:

Abstract

The concept of personalised medicine in cancer therapy is becoming increasingly important. There already exist drugs administered specifically for patients with tumours presenting well-defined genetic mutations. However, the field is still in its infancy, and personalised treatments are far from being standard of care. Personalised medicine is often associated with the utilisation of omics data. Yet, implementation of multi-omics data has proven difficult, due to the variety and scale of the information within the data, as well as the complexity behind the myriad of interactions taking place within the cell. An alternative approach to precision medicine is to employ a function-based profile of cells. This involves screening a range of drugs against patient-derived cells (or derivative organoids and xenograft models). Here we demonstrate a proof-of-concept, where a collection of drug screens against a highly diverse set of patient-derived cell lines, are leveraged to identify putative treatment options for a 'new patient'. We show that this methodology is highly efficient in ranking the drugs according to their activity towards the target cells. We argue that this approach offers great potential, as activities can be efficiently imputed from various subsets of the drug-treated cell lines that do not necessarily originate from the same tissue type.

Authors

  • Abbi Abdel-Rehim
    Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge CB3 0AS, United Kingdom.
  • Oghenejokpeme Orhobor
    The National Institute of Agricultural Botany, Cambridge CB3 0LE, United Kingdom.
  • Gareth Griffiths
    ValiRx Plc, Nottingham, UK.
  • Larisa Soldatova
    4Brunel University London, London, UK.
  • Ross D King
    3Department of Biology and Biological Engineering, Division of Systems and Synthetic Biology, Chalmers University of Technology, Kemivägen 10, SE-412 96 Gothenburg, Sweden.

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