the centre for applied genomics type genome centre founded 1998 headquarters toronto canada area served biomedical research key people dr. stephen w. scherer scientific director services experimentation project consultation data analysis bioinformatics number of employees 70 parent the hospital for sick children website http www.tcag.ca the centre for applied genomics is a genome centre in the research institute of the hospital for sick children and is affiliated with the university of toronto . tcag also operates as a science and technology innovation centre of genome canada 1 with an emphasis on next generation sequencing ngs and bioinformatics support . research at tcag focuses on the genetic and genomic basis of human variability health and disease including research on the genetics of autism spectrum disorder and structural variation of the human genome . the centre is located in the peter gilgan centre for research and learning in downtown toronto canada . contents 1 history 2 research 2.1 genome canada projects 2.2 databases 3 core facilities 3.1 informatics and biostatistics 3.2 dna sequencing and synthesis 3.3 microarray and genetic analysis 3.4 cytogenomics and genome resources 3.5 genetic analysis 3.6 biobanking 4 funding sources 5 organization and management 5.1 scientific director 5.2 scientific management committee 5.3 associate investigators 5.4 scientific advisory board 6 references 7 external links history edit the need for a centralized core facility for human genome research at sickkids hospital prompted the establishment of the centre for applied genomics tcag in 1998 . the founding director and associate director were drs. lap chee tsui and stephen w. scherer respectively . dr. scherer is now the scientific director . the centre for applied genomics mars location funding from the canada foundation for innovation cfi enabled tcag to form by consolidating existing core facilities including the medical research council of canada genome resource facility the canadian genetic diseases network cgdn large insert clone core the cgdn dna sequencing core and the sickkids biotechnology service dna sequencing and synthesis labs . a genome wide microsatellite genotyping laboratory at the ottawa health research institute led by dr. dennis bulman was added . subsequently operational funding from the cihr genomics special projects panel provided for additional staff . in 2001 a proposal entitled genome resource core platform was submitted to the then newly formed genome canada . this provided operational support enhancing existing facilities and adding a mouse genotyping core at the university of toronto led by dr. lucy osborne . in 2002 sickkids built a new affymetrix microarray facility . this core has quickly grown to become the largest such service centre in canada and is in the top ten in north america . 2 in 2004 tcag entered a second phase of development driven by a 12 million cfi ontario innovation trust funded project entitled integrative genomics for health research 3 allowing for consolidation of the mouse genotyping core with the sickkids facilities . this award also supported the establishment of an ontario population genomics repository opgp to be used as controls in studies of common diseases . to efficiently complete this project tcag partnered with dr. john mclaughlin s group at mount sinai hospital toronto . in may 2004 an application to the newly announced cfi research hospital fund resulted in a 10.9 million award to build out lab space and consolidate all operations on the 14th and 15th floors of the toronto medical discovery tower tmdt in the mars discovery district . tcag was the first occupant of tmdt in august 2005 quickly followed by other sickkids scientists . investments in computer infrastructure from the 2003 cfi ontario innovation trust competition resulted in the establishment of new phases of the high performance computing cluster hpf that is currently used by tcag and many other users to allow analysis of large genomic datasets arising from new microarray and sequencing technologies . further enhancements to the tcag infrastructure were supported by a 10.7 million renewal grant from cfi s leading edge fund competition entitled integrative genomics for health research phase ii awarded in june 2009 . 4 more recently a cfi grant entitled the centre for applied genomics paediatric genomes to outcomes provided further infrastructure support . 5 in october 2013 tcag moved to the peter gilgan centre for research and learning a new building housing the sickkids research institute . 6 tcag operates in large part on science and technology innovation centre stic funds from genome canada administered by the ontario genomics institute . research edit current research at tcag centres around large scale projects performed by facility personnel including support of genome canada projects and a significant focus on the genetics of autism spectrum disorders and structural variation of the human genome . service work is also performed for over 600 other academic private sector and government labs each year drawn from 30 different countries and spanning a wide variety of research disciplines . 7 past research at tcag is reflected by numerous peer reviewed scientific publications . in 2008 tcag scientific directors associate scientists and staff co authored 58 peer reviewed manuscripts dependent in some way either entirely or in part on the platform infrastructure as documented in pubmed . 8 since 2002 over 270 such papers have been published . 9 support of other researchers worldwide is found in many similar publications with at least 145 papers in scholarly journals book chapters or graduate thesis dissertations acknowledging support or use of database resources during 2008 alone . 10 historical papers include discovery of genes involved in predisposition to medulloblastoma michael taylor and james rutka with tcag support 11 gene identification in shwachman diamond syndrome with johanna rommens and others 12 gene identification in lafora epilepsy with berge minassian 13 and its canine counterpart 14 a disease relevant mecp2 isoform involved in rett syndrome 15 involvement of the sumo4 gene in type i diabetes 16 severe expressive language delay related to duplication of the williams beuren locus 17 tcag was also integral to publications describing the decoding of human chromosome 7 18 the discovery of large scale copy number variation in the human genome 19 20 and the analysis of the first diploid human genome sequence with the j. craig venter institute . 21 genome canada projects edit as a science and technology innovation centre of genome canada tcag currently supports numerous large scale projects including research on autism spectrum disorders structural variation of the human genome integrative biology conditional mouse mutagenesis interactions of signaling molecules type i diabetes cancer stem cells cystic fibrosis biodiversity structural biology and stem cells from genome canada s competition iii new technology development and applied genomics research in bioproducts or crops abc competitions . 22 23 24 the centre is now working with applicants in the large scale applied research project 25 and advancing technology innovation through discovery 26 competitions . databases edit tcag also hosts and curates websites and databases developed from supported projects namely the chromosome 7 database the database of genomic variants 27 the segmental duplication database the autism chromosome rearrangement database and others . 28 these databases contain publicly available information . core facilities edit tcag dna synthesis facility tcag employs a variety of genomic technologies to support different types of experimentation . these are organized into separate core facilities with dedicated managers . informatics and biostatistics edit the bioinformatics team assists with data handling and analysis and develops new algorithms and analytical methods with a focus on the analysis of high throughput next generation sequencing data . the statistical analysis group provides project consultation and power analysis statistical analysis genetic microarray and pathway data epidemiology population genetics and copy number variation analysis as well as developing new statistical methods . dna sequencing and synthesis edit the facility uses conventional capillary sanger sequencing on applied biosystems 3730xl instruments governed by a laboratory information management system lims . additionally next generation sequencing ngs using illumina hiseq 2500 and hiscan sq instruments life technologies ion proton and applied biosystems solid instruments and a 454 roche gs flx titanium instrument is performed . a key component of this facility is the use of high performance computing and bioinformatics support for ngs analysis . the oligonucleotide synthesis component of this facility makes conventional long up to 120 bases and modified oligonucleotides and purifies these by desalting cartridge or high performance liquid chromatography hplc . microarray and genetic analysis edit the microarray and gene expression core facility has a dedicated manager and operates technologies from affymetrix agilent and illumina . additionally there is a wide variety of analytical software packages available for on site data analysis . cytogenomics and genome resources edit the cytogenomics and genome resources core facility has a single manager between these two functions . cytogenomics includes karyotyping and spectral sky karyotyping for mouse human and other species fluorescent in situ hybridization fish mapping transgenic insertion site mapping g to fish mapping and clone labeling for fish experiments . the genome resources components includes a clone repository mammalian gene collection mgc cdna mouse and human genomic clones including human bacterial artificial chromosomes bacs and provides project consultation and design assistance annotation database queries probe selection . it also provides cdna library screening and quantitative pcr . genetic analysis edit the genetic analysis area includes capillary based genotyping applied biosystems taqman and snapshot microsatellites custom genotyping e.g. heteroduplex analysis mouse genotyping for cross progeny and genetic linkage analysis and methylation analysis for epigenetics research . biobanking edit the biobanking core facility has its own dedicated manager . it performs white cell immortalization from blood and banking fibroblast culture and banking culture and banking of other cell types including non human cells genomic dna preparation from blood saliva tissues or cells and whole genome amplification wga . funding sources edit tcag is funded by several agencies including the canada foundation for innovation cfi genome canada through the ontario genomics institute the ontario ministry of research and innovation . additionally philanthropic donations are administered by the hospital for sick children foundation and specific research projects are funded by a wide variety of agencies and charitable foundations . organization and management edit scientific director edit the scientific director of tcag is dr. stephen w. scherer senior staff scientist in the hospital for sick children s research institute director of the mclaughlin centre 29 and a professor at the university of toronto . 30 scientific management committee edit tcag is governed by a scientific management committee who meet regularly to discuss high level strategic planning . the scientific management committee consists of dr. gary bader dr. michael brudno dr. jayne danska dr. lisa strug dr. andrew paterson dr. peter ray dr. michael wilson drs. bader and brudno are located at the university of toronto and the others at the hospital for sick children brudno is also appointed at sickkids . the committee also includes three ex officio members the assistant director facility manager and a representative from the ontario genomics institute . associate investigators edit since 2006 tcag has appointed associate investigators . these associates consult on their specific areas of expertise and assist in identification and implementation of new technologies . at present there are seven associate investigators drs. ann george sickkids esteban parra utm mary shago sickkids mark silverberg msh james stavropoulos sickkids michael taylor sickkids and john vincent camh . scientific advisory board edit high level scientific oversight of tcag s scientific mandate and operations is provided through an external scientific advisory board sab . the sab members are dr. samuel levy chair genomic health dr. abdallah s. daar university of toronto dalla lana school of public health dr. mark daly whitehead institute dr. arend sidow stanford university the ontario genomics institute ogi and genome canada also provide ex officio members . references edit genome canada science and technology platforms data provided by affymetrix inc. integrative genomics for health research news item ontario innovation trust website 1 sickkids press release june 18 2009 sickkids kicks off 2013 with two leading edge fund grants january