Founded in 1998 by Canadian genomics pioneers Drs. Lap-Chee Tsui and Stephen Scherer, The Centre for Applied Genomics (TCAG) provides world-leading infrastructure, technical expertise, and experimental and informatics support for innovative research in genomics. TCAG is located on a full floor of the Research Institute of The Hospital for Sick Children (SickKids), in the Peter Gilgan Centre for Research and Learning in downtown Toronto, and is affiliated with the McLaughlin Centre and the University of Toronto. The centre is a founding member of Canada’s Genomics Enterprise (CGEn), a national genomics platform that is one of the Major Science Initiatives funded by the Canada Foundation for Innovation (CFI) as a national platform critical to Canada’s research success. Its friendly staff of approximately 100 includes highly skilled bioinformatics, statistics, and laboratory personnel, core facility managers, embedded researchers, Associate Investigators, and an administrative team. The group works closely with client scientists to ensure success of their projects.

TCAG contains individual core facilities that collectively form a full-service, end-to-end genomics pipeline that can accommodate projects from the very small to the very large. These include cores in Informatics & Biostatistics, Sequencing, Microarrays & Genotyping, and Cytogenomics & Biobanking. The facilities are run by highly experienced managers (with an average of 8 years in the role), who consult with TCAG clients to ensure optimum experimental approaches. Data are generated on a fee-for-service, cost-recovery basis, and belong to the client. TCAG data handling and analysis activities take advantage of the SickKids High Performance Computing Facility (HPF) and HPC4Health Compute Canada node, both housed in our PGCRL building, as well as cloud-based resources. The centre also developed and hosts the Database of Genomic Variants (DGV). Last year, the DGV website was visited over 230,000 times by users from 88 different countries and is cited in over 350 publications every year.

Importantly, TCAG supports projects across a wide variety of disciplines: not only human biomedical research, but also in areas as diverse as agriculture and agri-food, fisheries and oceans, biopharma research, translational diagnostics, public health, bioinformatics, biostatistics, environmental sciences and biodiversity, and many other disciplines. Work for client projects is acknowledged in hundreds of publications per year, from the over 800 Principal Investigator scientists using TCAG’s services annually.

There have been many milestones in TCAG’s long history, some of which are highlighted below:

• Since 2006, TCAG has provided services to over 2,200 laboratories: 85% from Canada including all ten Canadian Provinces; 45 countries; 331 academic institutions (universities, teaching hospitals and colleges); 157 companies (58% Canadian), and 49 government or NGO institutions. Dozens of trainees (students, fellows, visiting scientists, clinician-scientists, etc.) have trained within the facility.

• TCAG is the first genome centre in Canada to install and operate Illumina HiSeq X whole genome sequencers; these are run alongside Illumina NovaSeq and other HiSeq instruments, and many other technologies including those for single-cell genomics (10X Genomics Chromium), single-molecule, long-read nanopore sequencing (PacBio Sequel), sensitive quantitative detection methodologies (digital droplet PCR, qPCR), and an extensive slate of targeted genotyping (Agena, Taqman, etc.) and genomic analysis resources.

• TCAG developed the Ontario Population Genomics Platform repository that contains over 2,500 cell lines, DNA and demographic data from healthy controls, and has comprehensively genotyped over 850 of these. These data and population control DNA samples are available as a public resource.

• Under the leadership of current Director Stephen Scherer, and in collaboration with Google, Verily, BioTeam and DNAstack, TCAG leads the Autism Speaks “MSSNG” project, generating whole genome sequences from 10,000 members of families with autistic children. Over 8,000 genomes have been completed to date, with analysis of the first 5,200 reported in Nature Neuroscience. The capacity and capabilities built for MSSNG have resulted in many benefits to TCAG clients. One recent example is the development of an improved pipeline for whole-genome copy number variation analysis.

• TCAG has leveraged a total of over $223 million in funding over the past 20 years, including over $93 million in billed, cost-recovery services contributing to research studies in Canada and around the world. Major funding partners include CFI, the Ontario government’s Ministry of Research, Innovation and Science, Genome Canada, CIHR, the SickKids Foundation, and the McLaughlin Centre of the Unversity of Toronto.

Our group at The Centre for Applied Genomics will be pleased to help you with your research. Contacts for specific TCAG facilities can be found on our website. For general inquiries, please get in touch with TCAG’s Manager, Jo-Anne Herbrick, at (416) 813-8140, or jherbrick@sickkids.ca.

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.