Design of Biomedical Robots for Phenotype Prediction Problems

J Comput Biol. 2016 Aug;23(8):678-92. doi: 10.1089/cmb.2016.0008. Epub 2016 Jun 27.

Abstract

Genomics has been used with varying degrees of success in the context of drug discovery and in defining mechanisms of action for diseases like cancer and neurodegenerative and rare diseases in the quest for orphan drugs. To improve its utility, accuracy, and cost-effectiveness optimization of analytical methods, especially those that translate to clinically relevant outcomes, is critical. Here we define a novel tool for genomic analysis termed a biomedical robot in order to improve phenotype prediction, identifying disease pathogenesis and significantly defining therapeutic targets. Biomedical robot analytics differ from historical methods in that they are based on melding feature selection methods and ensemble learning techniques. The biomedical robot mathematically exploits the structure of the uncertainty space of any classification problem conceived as an ill-posed optimization problem. Given a classifier, there exist different equivalent small-scale genetic signatures that provide similar predictive accuracies. We perform the sensitivity analysis to noise of the biomedical robot concept using synthetic microarrays perturbed by different kinds of noises in expression and class assignment. Finally, we show the application of this concept to the analysis of different diseases, inferring the pathways and the correlation networks. The final aim of a biomedical robot is to improve knowledge discovery and provide decision systems to optimize diagnosis, treatment, and prognosis. This analysis shows that the biomedical robots are robust against different kinds of noises and particularly to a wrong class assignment of the samples. Assessing the uncertainty that is inherent to any phenotype prediction problem is the right way to address this kind of problem.

Keywords: biomedical robots; phenotype prediction; translational genomics; uncertainty assessment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis / drug therapy
  • Amyotrophic Lateral Sclerosis / genetics
  • Amyotrophic Lateral Sclerosis / pathology
  • Artificial Intelligence
  • Biomarkers / analysis*
  • Drug Discovery*
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Mutation
  • Myositis, Inclusion Body / drug therapy
  • Myositis, Inclusion Body / genetics
  • Myositis, Inclusion Body / pathology
  • Phenotype
  • Prognosis
  • Robotics / instrumentation
  • Robotics / methods*
  • Sequence Analysis, DNA / methods
  • Software

Substances

  • Biomarkers