title: In silico phenotyping via co-training for improved phenotype prediction from genotype.
abstract: BACKGROUND
  Predicting disease phenotypes from genotypes is a key challenge in medical applications in the postgenomic era. Large training datasets of patients that have been both genotyped and phenotyped are the key requisite when aiming for high prediction accuracy. With current genotyping projects producing genetic data for hundreds of thousands of patients, large-scale phenotyping has become the bottleneck in disease phenotype prediction.
  
  
  RESULTS
  Here we present an approach for imputing missing disease phenotypes given the genotype of a patient. Our approach is based on co-training, which predicts the phenotype of unlabeled patients based on a second class of information, e.g. clinical health record information. Augmenting training datasets by this type of in silico phenotyping can lead to significant improvements in prediction accuracy. We demonstrate this on a dataset of patients with two diagnostic types of migraine, termed migraine with aura and migraine without aura, from the International Headache Genetics Consortium.
  
  
  CONCLUSIONS
  Imputing missing disease phenotypes for patients via co-training leads to larger training datasets and improved prediction accuracy in phenotype prediction.
  
  
  METHODS
  The code can be obtained at: http://www.bsse.ethz.ch/mlcb/research/bioinformatics-and-computational-biology/co-training.html
authors.affiliation: Machine Learning and Computational Biology Lab, Department of Biosystems Science and Engineering, ETH Zurich, Switzerland, Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA, Program in Medical and Population Genetics and Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA, Department of Neurology and Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Damian
authors.initials: D
authors.lastname: Roqueiro
authors.affiliation: Machine Learning and Computational Biology Lab, Department of Biosystems Science and Engineering, ETH Zurich, Switzerland, Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA, Program in Medical and Population Genetics and Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA, Department of Neurology and Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Menno J
authors.initials: MJ
authors.lastname: Witteveen
authors.affiliation: Machine Learning and Computational Biology Lab, Department of Biosystems Science and Engineering, ETH Zurich, Switzerland, Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA, Program in Medical and Population Genetics and Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA, Department of Neurology and Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands Machine Learning and Computational Biology Lab, Department of Biosystems Science and Engineering, ETH Zurich, Switzerland, Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA, Program in Medical and Population Genetics and Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA, Department of Neurology and Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands Machine Learning and Computational Biology Lab, Department of Biosystems Science and Engineering, ETH Zurich, Switzerland, Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA, Program in Medical and Population Genetics and Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA, Department of Neurology and Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Verneri
authors.initials: V
authors.lastname: Anttila
authors.affiliation: Machine Learning and Computational Biology Lab, Department of Biosystems Science and Engineering, ETH Zurich, Switzerland, Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA, Program in Medical and Population Genetics and Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA, Department of Neurology and Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Gisela M
authors.initials: GM
authors.lastname: Terwindt
authors.affiliation: Machine Learning and Computational Biology Lab, Department of Biosystems Science and Engineering, ETH Zurich, Switzerland, Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA, Program in Medical and Population Genetics and Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA, Department of Neurology and Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands Machine Learning and Computational Biology Lab, Department of Biosystems Science and Engineering, ETH Zurich, Switzerland, Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA, Program in Medical and Population Genetics and Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA, Department of Neurology and Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Arn M J M
authors.initials: AM
authors.lastname: van den Maagdenberg
authors.affiliation: Machine Learning and Computational Biology Lab, Department of Biosystems Science and Engineering, ETH Zurich, Switzerland, Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA, Program in Medical and Population Genetics and Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA, Department of Neurology and Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Karsten
authors.initials: K
authors.lastname: Borgwardt
mesh_terms: D000465:Algorithms; D003198:Computer Simulation; D004194:Disease / Q000235:genetics*; D005838:Genotype; D060005:Genotyping Techniques / Q000379:methods*; D006801:Humans; D020325:Migraine with Aura / Q000175:diagnosis / Q000235:genetics; D020326:Migraine without Aura / Q000175:diagnosis / Q000235:genetics; D010641:Phenotype