AstraZeneca’s Centre for Genomics Research: towards new precision medicines
AstraZeneca’s Centre for Genomics Research (CGR) and the Institute for Genomic Medicine (IGM) have established a collaborative genomics alliance. This partnership will develop novel statistical genetics and computational methods, driving innovation in gene discovery from large whole exome and whole genome data sets. Large sequencing data sets will be generated from patient samples and, paired with corresponding patient clinical data, novel analytical methods will be applied to drive the development of innovative and impactful medicines for the right patients.
Specific computational areas of interest include the optimization of intolerance scoring methods refined to identify clinically relevant non-coding regulatory sequence in the genome, as well as regional intolerance in specific genes. These techniques will significantly advance the ability to interpret and identify pathogenic variants in genes, sub-regions of genes and non-coding regions of the genome, providing new insight into biological causes of disease.
Additional areas of focus involve the identification of biological pathways in disease through signal detection theory and developing methods to control for artifact in genome wide burden scores. Additionally, the IGM is supporting AstraZeneca in the design and implement of a cloud computing framework to support large scale statistical genetic analyses.
Together, the IGM and the AstraZeneca CGR will work to utilize large scale genomic data paired with statistical genetic and computational approaches to uncover disease mechanisms across a wide range of conditions, ultimately driving the development of new precision medicines.
Gene discovery and novel therapeutic approaches to treat neurological disorders
Biogen Idec and the Institute for Genomic Medicine have formed a strategic alliance to conduct research to determine the underlying genetic causes of disease and to identify new, targeted approaches to treatment. The collaborative work not only includes target identification and validation at the early stages of drug development but also facilitates genetically informed evaluation of treatments.
Together, Biogen Idec and the IGM are investigating the genomes of patients showing unusual treatment responses or unique disease presentations and are exploring the connections among genes, pathways, and disease processes, with focuses on Alzheimer’s disease and Amyotrophic Lateral Sclerosis (ALS).
The ultimate goal is to identify multiple qualified targets for new therapeutic approaches, ultimately increasing the potential for the development of new treatments and improved patient care.
Genetics, drug toxicity and efficacy in liver disease
Gilead is working with the IGM to research the role of genetics in drug toxicity and efficacy. Serious Adverse Events (SAEs) and treatment failure during antiviral therapy are significant issues in healthcare, and this partnership aims to understand the relationship between genetic variation and drug treatment outcomes.
The IGM-Gilead partnership is also investigating the role of genetics in the risk of liver disease and disease progression. Non-alcoholic Fatty Liver Disease (NAFLD) is a major cause of morbidity and mortality in the US, affecting up to 30% of the general population. Epidemiological studies have found that susceptibility to NAFLD and the risk of developing advanced liver disease are heritable, suggesting that there is a strong genetic component to the disease. Therefore, elucidating the genetic factors that influence the risk of NAFLD progression could identify biomarkers and illuminate the biological pathways associated with disease progression.
Gene discovery and Sequencing Clinics
UCB has partnered with the IGM to drive gene discovery in undiagnosed genetic conditions of childhood, with particular emphasis on patients with neuropsychiatric disorders such as seizures, autoimmune diseases, bowel disorders, allergies, respiratory complications and osteoporosis/skeletal conditions. For the past three years this partnership has supported “Sequencing Clinics” at Duke and Columbia University, and has funded the sequencing of patients collected worldwide. Many discovered variants are now actively being characterized at the molecular level to better understand how these mutations lead to disease, with the final goal of translating these discoveries rapidly into novel treatments.
Endoplasmic Reticulum (ER) Stress Disorders
A growing number of monogenic neurological diseases exhibit a clear etiology between ER stress and pathogenicity; however, no treatments are currently available. In collaboration with Janssen Pharmaceuticals, Inc. (a pharmaceutical company of Johnson & Johnson), we are focusing our efforts on the identification of new therapeutic targets and compounds pertaining to neurological diseases associated with ER stress. We will use human stem cell as well as non-stem cell models combined with small molecule screening to discover molecular mechanisms and potential therapeutic modes for these disorders.