Application of pharmacogenomics and bioinformatics to exemplify the utility of human ex vivo organoculture models in the field of precision medicine.

Here we describe a collaboration between industry, the National Health Service (NHS) and academia that sought to demonstrate how early understanding of both pharmacology and genomics can improve strategies for the development of precision medicines. Diseased tissue ethically acquired from patients suffering from chronic obstructive pulmonary disease (COPD), was used to investigate inter-patient variability in drug efficacy using ex vivo organocultures of fresh lung tissue as the test system. The reduction in inflammatory cytokines in the presence of various test drugs was used as the measure of drug efficacy and the individual patient responses were then matched against genotype and microRNA profiles in an attempt to identify unique predictors of drug responsiveness. Our findings suggest that genetic variation in CYP2E1 and SMAD3 genes may partly explain the observed variation in drug response.

Déclaration de conflit d'intérêts

REPROCELL Europe Ltd (https://www.reprocell.com/) is a commercial provider of laboratory based tests for preclinical research. KC, GM, MF and DCB are all paid employees of REPROCELL Europe. Aridhia (https://www.aridhia.com/) is a commercial provider of digital research environments for industry and academia. PB is a paid employee of Aridhia. Fios Genomics (https://www.fiosgenomics.com/) is a commercial provider of bioinformatics services. MB and SL are both paid employees of Fios Genomics. Sistemic (http://www.sistemic.co.uk/) is a commercial provider of miRNA focussed services. DM and EMG are both paid employees of Sistemic. These commercial affiliations do not alter adherence of the authors to PLOS ONE policies on sharing data and materials.