title: A physiome interoperability roadmap for personalized drug development.
abstract: The goal of developing therapies and dosage regimes for characterized subgroups of the general population can be facilitated by the use of simulation models able to incorporate information about inter-individual variability in drug disposition (pharmacokinetics), toxicity and response effect (pharmacodynamics). Such observed variability can have multiple causes at various scales, ranging from gross anatomical differences to differences in genome sequence. Relevant data for many of these aspects, particularly related to molecular assays (known as '-omics'), are available in online resources, but identification and assignment to appropriate model variables and parameters is a significant bottleneck in the model development process. Through its efforts to standardize annotation with consequent increase in data usability, the human physiome project has a vital role in improving productivity in model development and, thus, the development of personalized therapy regimes. Here, we review the current status of personalized medicine in clinical practice, outline some of the challenges that must be overcome in order to expand its applicability, and discuss the relevance of personalized medicine to the more widespread challenges being faced in drug discovery and development. We then review some of (i) the key data resources available for use in model development and (ii) the potential areas where advances made within the physiome modelling community could contribute to physiologically based pharmacokinetic and physiologically based pharmacokinetic/pharmacodynamic modelling in support of personalized drug development. We conclude by proposing a roadmap to further guide the physiome community in its on-going efforts to improve data usability, and integration with modelling efforts in the support of personalized medicine development.
authors.affiliation: Cyprotex Discovery Ltd , 15 Beech Lane, Macclesfield SK10 2DR , UK.
authors.forename: Simon
authors.identifier: 0000-0002-9979-081X
authors.initials: S
authors.lastname: Thomas
authors.affiliation: Leiden Institute of Advanced Computer Science , Leiden University , 111 Snellius, Niels Bohrweg 1, 2333 CA Leiden , The Netherlands.
authors.forename: Katherine
authors.identifier: 0000-0002-1279-5133
authors.initials: K
authors.lastname: Wolstencroft
authors.affiliation: Farr Institute, University College London, London NW1 2DA, UK; Auckland Bioengineering Institute, The University of Auckland, Auckland 1010, New Zealand.
authors.forename: Bernard
authors.identifier: 0000-0003-0638-5274
authors.initials: B
authors.lastname: de Bono
authors.affiliation: Auckland Bioengineering Institute , The University of Auckland , Auckland 1010 , New Zealand.
authors.forename: Peter J
authors.identifier: 0000-0001-9665-4145
authors.initials: PJ
authors.lastname: Hunter
keywords: data and model resources; human physiome; interoperability; personalized medicine; pharmacogenomics; physiologically based pharmacokinetic modelling