Machine learning and data mining frameworks for predicting drug response in cancer: An overview and a novel in silico screening process based on association rule mining.

Journal: Pharmacology & therapeutics
Published Date: Jul 30, 2019

Abstract

A major challenge in cancer treatment is predicting the clinical response to anti-cancer drugs on a personalized basis. The success of such a task largely depends on the ability to develop computational resources that integrate big "omic" data into effective drug-response models. Machine learning is both an expanding and an evolving computational field that holds promise to cover such needs. Here we provide a focused overview of: 1) the various supervised and unsupervised algorithms used specifically in drug response prediction applications, 2) the strategies employed to develop these algorithms into applicable models, 3) data resources that are fed into these frameworks and 4) pitfalls and challenges to maximize model performance. In this context we also describe a novel in silico screening process, based on Association Rule Mining, for identifying genes as candidate drivers of drug response and compare it with relevant data mining frameworks, for which we generated a web application freely available at: https://compbio.nyumc.org/drugs/. This pipeline explores with high efficiency large sample-spaces, while is able to detect low frequency events and evaluate statistical significance even in the multidimensional space, presenting the results in the form of easily interpretable rules. We conclude with future prospects and challenges of applying machine learning based drug response prediction in precision medicine.

Authors

  • Konstantinos Vougas
    Biomedical Research Foundation of the Academy of Athens, 4 Soranou Ephessiou Str., Athens GR-11527, Greece; Molecular Carcinogenesis Group, Department of Histology and Embryology, School of Medicine, National and Kapodistrian University of Athens, 75 Mikras Asias Str, Athens GR-11527, Greece.
  • Theodore Sakellaropoulos
    Department of Pathology, NYU School of Medicine, New York, NY 10016, USA; Laura and Isaac Perlmutter Cancer Center, NYU School of Medicine, New York, NY 10016, USA.
  • Athanassios Kotsinas
    Molecular Carcinogenesis Group, Department of Histology and Embryology, School of Medicine, National and Kapodistrian University of Athens, 75 Mikras Asias Str, Athens GR-11527, Greece.
  • George-Romanos P Foukas
    Molecular Carcinogenesis Group, Department of Histology and Embryology, School of Medicine, National and Kapodistrian University of Athens, 75 Mikras Asias Str, Athens GR-11527, Greece.
  • Andreas Ntargaras
    Molecular Carcinogenesis Group, Department of Histology and Embryology, School of Medicine, National and Kapodistrian University of Athens, 75 Mikras Asias Str, Athens GR-11527, Greece.
  • Filippos Koinis
    Molecular Carcinogenesis Group, Department of Histology and Embryology, School of Medicine, National and Kapodistrian University of Athens, 75 Mikras Asias Str, Athens GR-11527, Greece.
  • Alexander Polyzos
    Sanford I. Weill Department of Medicine, Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY 10021, USA.
  • Vassilios Myrianthopoulos
    Molecular Carcinogenesis Group, Department of Histology and Embryology, School of Medicine, National and Kapodistrian University of Athens, 75 Mikras Asias Str, Athens GR-11527, Greece; Division of Pharmaceutical Chemistry, School of Pharmacy, National and Kapodistrian University of Athens, Athens, Greece.
  • Hua Zhou
    Department of Biostatistics, UCLA.
  • Sonali Narang
    Department of Pathology, NYU School of Medicine, New York, NY 10016, USA; Laura and Isaac Perlmutter Cancer Center, NYU School of Medicine, New York, NY 10016, USA.
  • Vassilis Georgoulias
    Laboratory of Tumour Cell Biology, School of Medicine, University of Crete, Heraklion, Crete, Greece.
  • Leonidas Alexopoulos
    School of Mechanical Engineering, National Technical University of Athens, Zografou 15780, Greece.
  • Iannis Aifantis
    Department of Pathology, NYU School of Medicine, New York, NY 10016, USA; Laura and Isaac Perlmutter Cancer Center, NYU School of Medicine, New York, NY 10016, USA.
  • Paul A Townsend
    Division of Cancer Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, Manchester Cancer Research Centre, NIHR Manchester Biomedical Research Centre, University of Manchester, Manchester M20 4GJ, UK.
  • Petros Sfikakis
    Rheumatology Unit, Laikon University Hospital, Athens, Greece.
  • Rebecca Fitzgerald
    Medical Research Council Cancer Unit, Hutchison/Medical Research Council Research Centre, University of Cambridge, Cambridge, UK.
  • Dimitris Thanos
    Biomedical Research Foundation of the Academy of Athens, 4 Soranou Ephessiou Str., Athens GR-11527, Greece.
  • Jiri Bartek
    Genome Integrity Unit, Danish Cancer Society Research Centre, Strandboulevarden 49, Copenhagen DK-2100, Denmark; Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Hněvotínská, Olomouc 1333/5 779 00, Czech Republic; Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm SE-171 77, Sweden.
  • Russell Petty
    Division of Molecular and Clinical Medicine, Ninewells Hospital and School of Medicine, University of Dundee, Dundee DD1 9SY, Scotland.
  • Aristotelis Tsirigos
    Department of Pathology, NYU School of Medicine, New York, NY 10016, USA; Laura and Isaac Perlmutter Cancer Center, NYU School of Medicine, New York, NY 10016, USA; Applied Bioinformatics Laboratories, NYU School of Medicine, New York, NY 10016, USA. Electronic address: aristotelis.tsirigos@nyulangone.org.
  • Vassilis G Gorgoulis
    Biomedical Research Foundation of the Academy of Athens, 4 Soranou Ephessiou Str., Athens GR-11527, Greece; Molecular Carcinogenesis Group, Department of Histology and Embryology, School of Medicine, National and Kapodistrian University of Athens, 75 Mikras Asias Str, Athens GR-11527, Greece; Division of Cancer Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, Manchester Cancer Research Centre, NIHR Manchester Biomedical Research Centre, University of Manchester, Manchester M20 4GJ, UK; Center for New Biotechnologies and Precision Medicine, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Str, Athens GR-11527, Greece. Electronic address: vgorg@med.uoa.gr.

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