title: Design of Biomedical Robots for Phenotype Prediction Problems.
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.
authors.affiliation: 1 Artificial Intelligence Center, Universidad de Oviedo , Asturias, Spain .
authors.forename: Enrique J
authors.initials: EJ
authors.lastname: deAndrés-Galiana
authors.affiliation: 2 Mathematics Department, Universidad de Oviedo , Asturias, Spain .
authors.forename: Juan Luis
authors.initials: JL
authors.lastname: Fernández-Martínez
authors.affiliation: 3 Biomodels , LLC, Watertown, Massachusetts.
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Sonis
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D001185:Artificial Intelligence; D015415:Biomarkers / Q000032:analysis*; D055808:Drug Discovery; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D009154:Mutation; D018979:Myositis, Inclusion Body / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D010641:Phenotype; D011379:Prognosis; D012371:Robotics / Q000295:instrumentation / Q000379:methods*; D017422:Sequence Analysis, DNA / Q000379:methods; D012984:Software
chemical_list: D015415:Biomarkers
keywords: biomedical robots; phenotype prediction; translational genomics; uncertainty assessment