Phenotype inference in an Escherichia coli strain panel. 2017

Marco Galardini, and Alexandra Koumoutsi, and Lucia Herrera-Dominguez, and Juan Antonio Cordero Varela, and Anja Telzerow, and Omar Wagih, and Morgane Wartel, and Olivier Clermont, and Erick Denamur, and Athanasios Typas, and Pedro Beltrao
European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Hinxton, United Kingdom.

Understanding how genetic variation contributes to phenotypic differences is a fundamental question in biology. Combining high-throughput gene function assays with mechanistic models of the impact of genetic variants is a promising alternative to genome-wide association studies. Here we have assembled a large panel of 696 Escherichia coli strains, which we have genotyped and measured their phenotypic profile across 214 growth conditions. We integrated variant effect predictors to derive gene-level probabilities of loss of function for every gene across all strains. Finally, we combined these probabilities with information on conditional gene essentiality in the reference K-12 strain to compute the growth defects of each strain. Not only could we reliably predict these defects in up to 38% of tested conditions, but we could also directly identify the causal variants that were validated through complementation assays. Our work demonstrates the power of forward predictive models and the possibility of precision genetic interventions.

UI MeSH Term Description Entries
D010641 Phenotype The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment. Phenotypes
D005816 Genetic Complementation Test A test used to determine whether or not complementation (compensation in the form of dominance) will occur in a cell with a given mutant phenotype when another mutant genome, encoding the same mutant phenotype, is introduced into that cell. Allelism Test,Cis Test,Cis-Trans Test,Complementation Test,Trans Test,Allelism Tests,Cis Tests,Cis Trans Test,Cis-Trans Tests,Complementation Test, Genetic,Complementation Tests,Complementation Tests, Genetic,Genetic Complementation Tests,Trans Tests
D005838 Genotype The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS. Genogroup,Genogroups,Genotypes
D000073537 Biological Variation, Population Differences in measurable biological values, characteristics, or traits, among individuals of a population or between population groups. Between-Individual Biological Variation,Between-Person Biological Variation,Between-Person Variation,Between-Subject Biological Variation,Between-Subject Variation,Biologic Variability, Population,Inter-Individual Biological Variation,Phenotypic Variability,Phenotypic Variation,Between Individual Biological Variation,Between Person Biological Variation,Between Person Variation,Between Subject Biological Variation,Between Subject Variation,Between-Individual Biological Variations,Between-Person Biological Variations,Between-Person Variations,Between-Subject Biological Variations,Between-Subject Variations,Biologic Variabilities, Population,Biological Variation, Between-Individual,Biological Variation, Between-Person,Biological Variation, Between-Subject,Biological Variation, Inter-Individual,Biological Variations, Between-Individual,Biological Variations, Between-Person,Biological Variations, Between-Subject,Biological Variations, Inter-Individual,Biological Variations, Population,Inter Individual Biological Variation,Inter-Individual Biological Variations,Phenotypic Variabilities,Phenotypic Variations,Population Biologic Variabilities,Population Biologic Variability,Population Biological Variation,Population Biological Variations,Variabilities, Phenotypic,Variabilities, Population Biologic,Variability, Phenotypic,Variability, Population Biologic,Variation, Between-Individual Biological,Variation, Between-Person,Variation, Between-Person Biological,Variation, Between-Subject,Variation, Between-Subject Biological,Variation, Inter-Individual Biological,Variation, Phenotypic,Variation, Population Biological,Variations, Between-Individual Biological,Variations, Between-Person,Variations, Between-Person Biological,Variations, Between-Subject,Variations, Between-Subject Biological,Variations, Inter-Individual Biological,Variations, Phenotypic,Variations, Population Biological
D014644 Genetic Variation Genotypic differences observed among individuals in a population. Genetic Diversity,Variation, Genetic,Diversity, Genetic,Diversities, Genetic,Genetic Diversities,Genetic Variations,Variations, Genetic
D048168 Escherichia coli K12 A species of gram-negative, rod-shaped bacteria belonging to the K serogroup of ESCHERICHIA COLI. It lives as a harmless inhabitant of the human LARGE INTESTINE and is widely used in medical and GENETIC RESEARCH. E coli K12

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