title: Applications of omics approaches to the development of microbiological risk assessment using RNA virus dose-response models as a case study.
abstract: The last decade has seen a huge increase in the amount of 'omics' data available and in our ability to interpret those data. The aim of this paper was to consider how omics techniques can be used to improve and refine microbiological risk assessment, using dose-response models for RNA viruses, with particular reference to norovirus through the oral route as the case study. The dose-response model for initial infection in the gastrointestinal tract is broken down into the component steps at the molecular level and the feasibility of assigning probabilities to each step assessed. The molecular mechanisms are not sufficiently well understood at present to enable quantitative estimation of probabilities on the basis of omics data. At present, the great strength of gene sequence data appears to be in giving information on the distribution and proportion of susceptible genotypes (for example due to the presence of the appropriate pathogen-binding receptor) in the host population rather than in predicting specificities from the amino acid sequences concurrently obtained. The nature of the mutant spectrum in RNA viruses greatly complicates the application of omics approaches to the development of mechanistic dose-response models and prevents prediction of risks of disease progression (given infection has occurred) at the level of the individual host. However, molecular markers in the host and virus may enable more broad predictions to be made about the consequences of exposure in a population. In an alternative approach, comparing the results of deep sequencing of RNA viruses in the faeces/vomitus from donor humans with those from their infected recipients may enable direct estimates of the average probability of infection per virion to be made.
authors.affiliation: Animal Health and Veterinary Laboratories Agency, Surrey, UK.
authors.forename: P
authors.initials: P
authors.lastname: Gale
authors.forename: A
authors.initials: A
authors.lastname: Hill
authors.forename: L
authors.initials: L
authors.lastname: Kelly
authors.forename: J
authors.initials: J
authors.lastname: Bassett
authors.forename: P
authors.initials: P
authors.lastname: McClure
authors.forename: Y
authors.initials: Y
authors.lastname: Le Marc
authors.forename: I
authors.initials: I
authors.lastname: Soumpasis
mesh_terms: D018450:Disease Progression; D060467:Disease Resistance; D023281:Genomics; D006801:Humans; D008957:Models, Genetic; D012327:RNA Virus Infections / Q000235:genetics / Q000821:virology*; D012328:RNA Viruses / Q000235:genetics / Q000502:physiology*; D011991:Receptors, Virus / Q000378:metabolism; D018570:Risk Assessment / Q000379:methods; D053586:Virus Internalization; D014779:Virus Replication
chemical_list: D011991:Receptors, Virus
keywords: dose-response; genetic susceptibility; infection; norovirus; omics