and Clinical Biomarker Validation
Epistem's pharmacogenomics division have provided biomarker discovery and validation studies with many sponsors. The bespoke nature of many of Epistem's services mean that bioinformatics analysis is always tailored to the nature of the study. Indeed many of Epistem's CRO services also filter into pharmacogenomics often relying on creative methods of analysis.
Epistem offer a stand-alone bioinformatics analysis for many standard big‑data generating projects. Dr Elliott Harrison, Head Bioinformatician at Epistem, has summarised some data we have generated, using a case study where a PI3 kinase inhibitor signature was identified, and progressed as a biomarker in clinical samples.
To demonstrate proof of concept, plucked anagen hairs from four healthy normal volunteers were cultured in the presence or absence of a panPI3K inhibitor for 24 hours. RNA was extracted and amplified using Epistem's RNA-Amp™ amplification technology. cDNA was synthesised and hybridised to whole genome microarrays.
We used this probe set as a multivariate signature to define a score for PI3K inhibition (or PI3K/mTOR inhibition) to validate its potential as a clinical biomarker in hair. The signature was also assessed in non-hair assays and included commercially available PI3K inhibitors to demonstrate multi‑model predictability.
The signature was also assessed in a clinical setting. RNA was extracted and amplified from plucked anagen hairs from individuals enrolled onto the sponsor's clinical trial. cDNA was synthesised and hybridised to whole genome microarrays.
Drilling down further into the PI3K inhibition gene signature our bioinformaticians identified a number of biologically relevant genes to test as clinical biomarkers. Microarray data from both the ex vivo hair study and the clinical hair data demonstrated that genes identified in the ex vivo experiment predicted PI3K inhibitor response in the clinical samples.
This case study demonstrates the validation of a clinical biomarker from the very first proof of concept stages. This study exemplifies some of the creative thinking and know‑how utilised by Epistem's pharmacogenomics and bioinformatics unit.