Open Targets employs large-scale human genetics and genomics data to change the way drug targets are identified and validated. We have established a set of interlinking projects to develop both the data and analytical processes that implicate targets as valid, and the core platform to provide the information to a diverse audience of users. We are developing 2 major areas of work, which in each case can be further subdivided into individual workstreams. The major areas are the core bioinformatics platforms, including pipelines and a database to integrate existing target validation data as well as a public web portal to serve the integrated views, and experimental projects which will generate new data to feed into the database.
We have established a portfolio of experimental projects that we believe will provide target validation information relevant to key therapeutic areas. Our approach is to use high throughput methodologies that can address as near as possible the full range of relevant targets (ideally the whole genome) in systems that are relevant to the physiology of diseases with high unmet need. As such we have identified oncology, inflammatory bowel diseases (IBD), respiratory disease, inflammation and immunity as suitable therapeutic areas because in addition to the pressing need for developments in these areas due to disease burden, there is complementary expertise between the partners’ research interests.
We are using methods that provide cross cutting themes across multiple therapeutic areas. We have chosen to focus on the use of genetics as a tool for target identification and validation, and subsequent exploitation of cellular models of disease through the new gene editing technologies or single cell analysis. We are investigating the use of large populations and approaches such as Mendelian Randomisation including for metabolomic and proteomic data. In addition to clinical samples, iPS cells and cellular organoids are resources that can provide cellular phenotyping at scale with more physiological relevance than transformed cell lines.
We leverage the power of our partners’ data analyses and annotation to integrate information about common and rare diseases. Our work on core components and pipelines forms the backbone of information and display for the Open Targets Platform, and encompasses any type of data that is relevant to human disease biology.
We have established a portfolio of experimental projects that will provide target identification and prioritisation information relevant to key therapeutic areas. Our approach is to use high throughput methodologies that can address as near as possible the full range of relevant targets (ideally the whole genome) in systems that are relevant to the physiology of diseases with high unmet need.
We use genomic data from clinical cancer research to identify ‘driver’ genes in many types of cancer. This guides the way we interpret experimental results, and helps us identify potential drug targets and clinically relevant associations. To maximise the usefulness of our results, we prioritise tumour types and mutations most in need of clinical investigation.
Open Targets has developed state-of-the-art analysis methods for its immunology focus, which includes inflammatory bowel disease (IBD). These projects will validate candidate targets experimentally in gut tissue. Our immunology work benefits from access to the UK’s IBD BioResource, which collects DNA, biopsies and stool for genomic studies. We will expand this work into the area of asthma research, using single-cell genomics.
Using gene-editing techniques on neurons derived from induced-pluripotent stem cells, we are identifying factors that influence oxidative stress response and Tau uptake including mutations specific to Alzheimer’s disease. Using the same neuron systems, we are also using genome-wide association studies of Alzheimer’s and Parkinson’s disease to identify and test potential targets.