Research in Focus: Pharmaceutical Sciences Sequencing Centre

ISSUE FOUR: MARCH 2014

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FOCUS Pharmaceutical Sciences Sequencing Centre sequencing.ubc.ca

Dr. Corey Nislow Dr. Ronald Reid Mark Kunzli

Pharmaceutical sciences sequencing centre The Pharmaceutical Sciences Sequencing Centre is an end-to-end genetic analysis pipeline that enables our research. Our state-of-the-art technology allows us to develop and utilize customized solutions for sequencing, bioinformatics analysis and clinical application with rapid turnaround times.

Lab Members Corey Nislow, Principal Investigator Ronald Reid, Principal Investigator Mark Kunzli, Principal Investigator, Project Manager Sunita Sinha, Lab Manager Emma Kim, Undergraduate Student iNTRODUCTION Pharmacogenomics is the study of how genes affect an individual’s response to pharmaceutical agents. While pharmacogenomics is known to play an important role in determining medication response, avoiding adverse drug events and optimizing dosage; clinical application is not currently part of day-to-day health care. Translational and Applied Genomics (TAG) projects are designed to develop, utilize and evaluate infrastructure enabling the application of pharmacogenomic data in pharmacy practice. Our overriding goal is to translate the advances in next-generation sequencing (NGS) technology into improved health outcomes.

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SELECTED PROJECTS Reducing Adverse Drug Reactions caused by 2nd Generation Antipsychotics: Promoting Innovative Pharmacy Practice through Precision Therapy Concern over the misuse of the atypical antipsychotics olanzapine and risperidone in young adults (240,000 prescriptions for risperidone alone for children 12 and under in 2011) has been expressed in no uncertain terms to the FDA during a review of these second generation atypical antipsychotics (SGAs). No atypical antipsychotic has been approved for prescription to children for any indication although they are frequently prescribed for ADHD or other behavioural disorders. Equally worrisome is that no long-term studies of these drugs on brain development have been performed. The expert consensus is that these drugs are too readily prescribed by doctors unfamiliar with their potency and side effect profile: substantial weight gain, metabolic disorders and muscular tics that can be permanent. Finally, practical application of pharmacogenomic information relevant to these drugs is nearly non-existent.

This project, sponsored by the College of Pharmacists of BC, is focused on detecting genetic variations implicated in adverse reactions (ADRs) occurring during therapy with the SGAs olanzapine and risperidone while developing an exome database of 200 community pharmacy practice patients. Our complementary objective is to demonstrate that the community pharmacist is in the best position to acquire, assess, and utilize genetic information to optimize drug therapy. In order to facilitate the recruitment and phenotyping of patients, this project is designed to develop and evaluate an infrastructure through which pharmacogenomic data can be applied by the community pharmacist to optimize second-generation antipsychotic drug therapy.

Genomics for Precision Drug Therapy in the Community Pharmacy Rapid, inexpensive, next-generation sequencing will revolutionize health care and empower patients and their healthcare providers by providing a comprehensive record of each individual’s genetic disposition. This project will develop Standard Operating Procedures (SOPs) for: i) patient recruitment, education and informed consent; ii) collection and documentation of patient saliva samples and therapeutic phenotyping by pharmacists in community pharmacies; iii) genetic analysis, processing RESEARCH IN FOCUS · 3

of data, and information storage in a secure database; and iv) training of pharmacists in the retrieval and utilization of patient genetic information to optimize therapy and maintain wellnes.

In addition to developing a clear path for sample collection and analysis, a significant added value of this proposal is its educational component.

By establishing this role of delivering pharmacogenomic information to the community pharmacist, the power and impact of genetic advances can be conveyed to the client in a non-urgent, educational setting. We are using anticoagulation therapy as the model to demonstrate this approach for several reasons: i) the therapeutic window for several of the currently prescribed anticoagulant drugs is narrow; ii) the cost difference between therapeutic alternatives is large; and iii) this area is one of only a small number in which genetic testing is recommended by the US Federal Drug Administration.

This study, in partnership with the BC Pharmacy Association, will incorporate genotyping of 18 variants in 5 candidate genes from the Vitamin K coagulation cycle. Specifically, samples will be processed for DNA extraction such that an array of DNA-based readouts including, PCR or whole exome sequencing (WES) can be performed. Initially, PCR-based tests will be performed on all samples and WES on a subset of the samples. This twopronged approach will allow for essential quality control of the sequence data and will ensure that validation and implementation of SOPs for WES is completed during the course of this project.

Patient stratification algorithm based on pharmacogenomics.

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COLLABORATIONS In addition to our featured projects, we also have also established collaborations with: 1. The Centre for Drug Research and Development – To act as the hub of their Next Generations Genomics Node.

2. The BC Generations Project – To perform quality control for sequencing of biological samples.

3. Microsoft Surface – To analyze the utilization of Surface tablets in community pharmacy-based research projects.

4. Microsoft HealthVault – To develop the HeathVault software capabilities to display and utilize genomic information.

Relevant Publications Kunzli M, Reid R, Riggs KW. Pharmacogenomics, personalized medicine, and patient-centric therapy: The pharmacist’s role in the genomic evolution.

Pharm Pract. 2012 Dec 1.

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TECHNOLOGY Next-Generation Sequencing: Illumina HiSeq 2500 The HiSeq 2500 features two run modes (rapid run and high output run) and the ability to process one or two flow cells simultaneously. This provides a flexible and scalable platform that supports the broadest range of applications and study sizes. Rapid run mode provides quick results, while high output mode is used for larger studies with more samples or when the greatest depth of coverage is required.

Illumina MiSeq The MiSeq offers the shortest sample-todata workflow, capable of producing 2 x 300 paired-end reads and up to 15 Gb of data in a single run. This allows assembly of small genomes or detection of target variants with unmatched accuracy.

Bioinformatics: Knome knoSYS™100

The knoSYS™100 is equipped with knoSOFT, an advanced decision support application for managing sequence data through the informatics pipeline, filtering variants, running gene panels, classifying/interpreting variants, and reporting results.

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Services Illumina HiSeq 2500 The HiSeq 2500 System is a powerful and efficient ultra-high-throughput sequencing system that supports the broadest range of applications and study sizes. Unrivaled data quality using Illumina’s proven SBS chemistry has made the HiSeq 2500 the instrument of choice for all major genome centers and leading institutions throughout the world.

Illumina MiSeq The MiSeq desktop sequencer allows you to access more focused applications such as targeted gene sequencing, metagenomics, small genome sequencing, targeted gene expression, amplicon sequencing, and HLA typing. knoSYS™100 The knoSYS™100 seamlessly integrates an interpretation application (knoSOFT) and informatics engine (kGAP) with a high-performance grid computer. Designed for whole genome, exome, and targeted NGS data, the knoSYS™100 helps labs quickly go from reads to reports.

Library Preparation In addition to sequencing, we offer library preparation using Illumina’s Nextera XT and TruSeq technologies. We also accept user-prepared libraries as long as they are compatible with our system. For such libraries, certain QC metrics are required.

We strive to achieve a turnaround time of 4 weeks from library quality control to run initiation. We offer a variety of accelerated services at extra cost.

Pricing Contact for quote: sequencing.centre@ubc.ca

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Learn more about research at UBC Pharm Sci The University of British Columbia is one of the most respected research institutions in the world. To learn more about the ground-breaking health science research happening at the Faculty of Pharmaceutical Sciences, visit http://www.pharmacy.ubc.ca/research/overview

University of British Columbia Faculty of Pharmaceutical Sciences 2405 Wesbrook Mall, Vancouver, B.C. V6T 1Z3 www.pharmacy.ubc.ca