The Network Biology Collaborative Centre (NBCC) at the Lunenfeld-Tanenbaum Research Institute assists scientists with connecting information on genomic and phenotypic variation in health and disease with a functional understanding of how gene products convey biological information and how their alterations drive disease. The Centre provides critical added value to Canada\’s genomics enterprise by offering an integrated suite of resources that support the discovery and validation of targets and disease mechanisms. To fulfill this mandate, the NBCC incorporates key proteomics technologies that allow users to map dynamic physical interactions between proteins on either a small or large scale in either cell lines or tissues. This is a powerful strategy to gain insight into the biological function of poorly studied proteins, so-called “guilt-by-association”. Protein networks can then be functionally interrogated by systematically depleting specific nodes from a cell or tissue system, for instance by RNA interference or by CRISPR gene editing, and the impact on a myriad of cell behaviours can then be assessed by end-point assays, sophisticated automated microscopy, super-resolution microscopy (to provide for detailed analysis of tissue and subcellular structures) or by evaluating impact on transcriptomes. Extensive resources to perturb networks using targeted chemical probes are also utilized to provide another powerful dimension to understanding how biological networks control cell function. NBCC resources thus allow users to rapidly reveal new disease gene functions, uncover novel pathways driving disease pathology and establish rational bases for the design of therapeutic strategies in the clinic.

The NBCC traces its roots back to 1999 with the establishment of one of the first proteomics mass spectrometry facilities in Canada and the development of one of the first academic screening centres. In 2014, these facilities were amalgamated into the Network Biology Collaborative Centre to provide Canadian scientists with integrated services in functional genomics, chemical genetics and proteomics. The NBCC subsequently expanded with new offerings in high spatio-temporal resolution imaging and next-generation sequencing. The Centre is directed by Drs. Jeff Wrana and Anne-Claude Gingras with expert input from co-investigators Drs. Laurence Pelletier and Daniel Durocher. Together, they provide unparalleled expertise in genetic and chemical screens, protein interactions and networks, advanced imaging, and transcriptomics.  Since its amalgamation, the NBCC has contributed to >100 publications with over 25% being in prestigious journals (Cell, Molecular Cell, Science, Nature family journals). These publications have resulted from collaborations with >175 Principal Investigators across Canada and internationally.

The NBCC operates through multiple complementary nodes: proteomics, high-throughput screening, next-generation sequencing, and high-content to high-resolution imaging. Each of these nodes is managed by an experience technical expert with oversight provided by Centre Manager Dr. Karen Colwill. The proteomics node has unique expertise in functional proteomics, particularly protein-protein interactions, where validated experimental approaches are combined with a unique and robust computational platform. This pipeline dovetails with the high-throughput screening (HTS) node, which incorporates sophisticated automated robotics and sample management. This enables the physical and functional interrogation of mammalian systems through application of an extensive collection of cDNA libraries, RNA interference resources and small molecule libraries. Complementing these two nodes, a suite of high-content, automated imaging and high spatial-temporal resolution instruments permit various screening modalities. Lastly, our next-generation sequencing node specializes in transcriptomics and CRISPR pooled screening support. The NBCC provides not only its extensive expertise in the design and application of sophisticated screening strategies through these nodes, but also its ability to integrate these screens with each other to drive biological insights. Customers often enter the NBCC through one node, e.g. HTS that identifies genes with interesting phenotypes, then move to imaging to obtain detailed phenotypical readouts and proteomics to identify interaction partners; this enables rapid transition from target identification to functional insight; a unique strength of the NBCC.

The NBCC has been funded as a technology platform by Genome Canada, through Ontario Genomics, since 2015, with a recent investment of $5 million in 2017 for operation support and technology development.   With this funding, the Centre is incorporating new capabilities into the Centre to better model health and disease states. The NBCC will establish next generation screening modalities by pairing CRISPR-based screening with more complex readouts including single cell sequencing and imaging-based phenotyping. Chemical screening capabilities will be extended by adding a chemical proteomics pipeline to identify proteins targeted by compounds of interest. Finally, data management and analytics across all the NBCC nodes will be expanded and strengthened to allow users to rapidly extract mechanistic insight into their biological and disease models. These improvements will help ensure that future NBCC users remain internationally competitive and drive their science to realize the greatest benefit.

Major advances in genomics and informatics over the past several years have resulted in individual research projects producing enormous amounts of data. In particular, genomic data from large population and clinical cohorts, coupled with extensive health and lifestyle data, have the potential to generate critical biological insights into human health and novel determinants of disease. These technological developments have emerged as a new challenge for researchers because advances in genomics will be made (or limited) by bioinformatics analytical capacity and the ability to store and analyze data in new and more sophisticated ways.

The Canadian Data Integration Centre was established to help translate the biological research insights into tangible improvements for patients with cancer and chronic disease. Genome Canada recently renewed its commitment to the Canadian Data Integration Centre (CDIC), with a $6.4 million investment to establish a Genome Canada’s Genome Technology Platforms. Housed at the Ontario Institute for Cancer Research (OICR), the CDIC offers opportunities for cutting-edge pan-disease health research and big data analytical approaches.

As Canada’s first public site to offer third generation bioinformatics and genomics tools to support both functional and clinical genomics, the CDIC has emerged as a tried-and-tested solution for challenges faced in the application and management of advanced sequencing technologies, pathology and biospecimen handling, genomics, and data integration. This is evidenced by the platform supporting large-scale health and research initiatives such as the International Cancer Genome Consortium and Canada’s largest population cohort and precision health program, the Canadian Partnership for Tomorrow Project.

The CDIC is led by Dr. Philip Awadalla (Director of the CDIC and CPTP), and co-investigators Lincoln Stein, Jared Simpson, Vincent Ferretti and John Bartlett, bringing together a team of international experts on the collection, harmonization and publication of genomic and phenomic data. Together, they are able to provide the full breadth of support for projects ranging from the initial design, collection and analysis of complex data, through to the development of integrated data portals to facilitate data sharing and the translation of research findings into tangible health outcomes. The CDIC provides client-oriented access services that are customizable to diverse research areas, such as genomics, epigenetics and population level studies, in addition to supporting biopharmaceutical initiatives in biomarkers discovery, drug development and repurposing. Having supported some of the world’s largest programs in data analysis and hosting, including the NCI Cancer Genomic Data Commons and the Pan-Cancer Analysis of Whole Genomes Consortium, the platform has been established as an international leader in genomics, informatics, and translational research.

To date, the CDIC has attracted more than $87 million in grants and generated $14 million in service revenue through providing bespoke support for local and international projects. This has culminated in numerous high-impact publications in Nature, Science and Nature family journals, including a recent study featured in Nature Communications, and highlighted in the Globe and Mail, showing that environmental exposures are more determinant of respiratory health outcomes than inherited genetics.

The investment through Ontario Genomics will support the expansion of the CDIC’s services to include the genomic infrastructure supported by OICR’s Genome Technologies and Diagnostics teams. The informatics and bio-computing core at the CDIC is currently the largest academic cancer informatics program in Canada, offering real-time, long-read PromethION direct sequencing technology, Chromium 10X single cell library preparation and is proudly home to the first operational NovaSeq in Ontario. This allows the CDIC to equip researchers and industry clients alike with state-of-the-art software and analytical tools to interrogate the underlying causes of complex diseases. As CDIC researchers help to facilitate a new era of Canadian-led genomics and informatics research projects, they will develop novel technologies and methodologies for long-read sequencing, facilitate the development and clinical roll-out of therapeutic biomarkers and streamline the translation of research innovations to the clinical context. With this renewed commitment from Genome Canada, the CDIC looks forward to supporting national and international efforts to better combat cancer, chronic and infectious disease.