NIHR/BRC Vacation Studentship - Summer 2015
Student: Andreas Millios
Supervisor(s): Dr Chiara Bacchelli
Title of Project: "Reducing Immunosuppressant Adverse Drug Reactions: A proof-of-principle pharmacogenomic
study in a paediatric cohort"
Project description and results:
These past six weeks I was very fortunate to experience the amazing opportunity of carrying out a research
project at GOSgene, within the Center of Translational Genomics of the Institute of Child Health (ICH). The main
aim of my research was to facilitate the identification of novel pathogenic genetic variants responsible for rare
diseases, using innovative technologies such as Next Generation Sequencing, linkage analysis and web-based
diagnostic programs. The ongoing research in GOSgene is critical to understand the pathophysiology of rare
diseases, identify potential therapeutic targets, discover novel biomarkers, and ultimately evaluate treatments
and therapies.
My workplan included the analysis of whole exome data from 3 patients suffering from the rare congenital
disorder known as Bardet-Biedl Syndrome, using different filtering strategies for the isolation of putative
disease-causing mutations. Once potential variants were identified, further bioinformatics analysis was
undertaken to evaluate whether variants were likely to be pathogenic.For this to be done, web-accessible tools
such as SIFT and Polyphen2 were used to predict the impact of a mutation on the protein structure, and
therefore, its change in function. This approach highlights the most relevant variants likely to cause the disease.
Sequence analysis software such as Qiagen’s Ingenuity Variant Analysis were used to accelerate the process by
incorporating filtering mechaninsms with integrated live genetic database access. The pertinent variants were
filtered according to quality considerations by adjusting call-confidence and read-depth thresholds. The
software can also allocate priority to variants within genes that are known to interact with other known
predisposition genes present within a gene network. Subsequently, the few genetic variants highlighted by the
software as the most promising, had to be amplified using PCR and further validated by Sanger sequencing to
rule out the possibility of artefacts.
Nevertheless, this summer has been more than just a research project. ICH is more than a centre of biomedical
research; it is truly a scientific community encouraging both scientific and personal growth. To conduct first-rate
research using the laboratory’s state-of-the-art facilities, learn the scientific process, technical methods and
then communicate the discoveries to other renowned scientists, is every young scientist’s vision. I humbly
believe that this experience has been invaluable in reinforcing my ambition of pursuing a future direction in
translational genomics and personalised medicine.