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


Autoři: Karen Cowan aff001;  Graeme Macluskie aff001;  Michael Finch aff001;  Colin N. A. Palmer aff002;  Jane Hair aff003;  Max Bylesjo aff004;  Sarah Lynagh aff004;  Pamela Brankin aff005;  Marian McNeil aff006;  Carolyn Low aff006;  David Mallinson aff007;  Elaine M. Gourlay aff007;  Hannah Child aff006;  Linda Cheyne aff006;  David C. Bunton aff001
Působiště autorů: REPROCELL Europe Ltd, Thomson Pavilion, Glasgow, Scotland, United Kingdom aff001;  School of Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, Scotland, United Kingdom aff002;  NHS Greater Glasgow & Clyde, Queen Elizabeth University Hospital, Glasgow, Scotland, United Kingdom aff003;  Fios Genomics Ltd, Nine Edinburgh Bioquarter, Edinburgh, Scotland, United Kingdom aff004;  Aridhia Informatics Ltd Teaching and Learning Building, Queen Elizabeth University Hospital, Glasgow, Scotland, United Kingdom aff005;  Stratified Medicines Scotland Innovation Centre, Teaching and Learning Building, Queen Elizabeth University Hospital, Glasgow, Scotland, United Kingdom aff006;  Sistemic Ltd, West of Scotland Science Park, Glasgow, Scotland, United Kingdom aff007
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0226564

Souhrn

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.

Klíčová slova:

Bioinformatics – Biopsy – Drug research and development – Genome-wide association studies – Chronic obstructive pulmonary disease – MicroRNAs – RNA extraction – Variant genotypes


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Článek vyšel v časopise

PLOS One


2019 Číslo 12