The 2nd Deep Learning and Artificial Intelligence Winter School 2018
10th – 13th December 2018, Bangkok, Thailand

Richard Wintle
Assistant Director, The Centre for Applied Genomics, The
Hospital for Sick Children, Toronto, Canada
Associate Scientific Director, CP-NET Cerebral Palsy
Integrated Discovery Program

Topic: Detecting structural variation from whole genome sequence data: application toneurodevelopmental disorders
Abstract:
Variation within the human genome can take many forms, the most commonof which include single nucleotide variation (SNV), short insertions/deletions (indels),and large-scale copy number variation (insertions, deletions; CNV). Rarer structuralvariations (SV) can include translocations, translocational insertions, inversions, and complex
events (such as translocations with deletions or duplications at the breakpoints). There
are robust and established methods for detecting CNV from genome-wide microarray
data, and for detecting SNV and indels from sequence data. However, detection of CNV
and in particular, SV, from whole genome sequence (WGS) data are not yet optimal,
particularly for complex events. Here, we will discuss recent work at The Centre forApplied Genomics (TCAG; www.tcag.ca), in particular centred around our recent
publication of optimized CNV methods. We will also highlight newer work using
anomalous paired-end and split read methods to resolve breakpoints, and touch on theutility of deep learning methods to refine CNV boundaries. These methods form partof TCAG’s integrated pipeline for analysis of WGS data from a number ofneurodevelopmental disorder projects, most notably the MSSNG project that is
examining the genomes of 10,000 subjects from families with autism spectrum disorder.
Reference:• Trost B, Walker S, Wang Z, Thiruvahindrapuram B, MacDonald JR, Sung WWL,Pereira SL, Whitney J, Chan AJS, Pellecchia G, Reuter MS, Lok S, Yuen RKC,Marshall CR, Merico D, Scherer SW (2018).
• A Comprehensive Workflow for Read Depth-Based Identification of Copy-Number
Variation from Whole-Genome Sequence Data. Am J Hum Genet. 102(1):142-155.
doi: 10.1016/j.ajhg.2017.12.007. PMID: 29304372 Article available athttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5777982/.
Bio:Dr. Wintle’s scientific interests lie in the application of genomic technologies to theunderstanding of individual genetic variability, with a specific focus on the neuromotor
condition, Cerebral Palsy. He serves as both Associate Scientific Director of the CP-NETCerebral Palsy Integrated Discovery Program within Ontario, Canada, and as a founding

The 2nd Deep Learning and Artificial Intelligence Winter School 2018
10th – 13th December 2018, Bangkok, Thailand

member of the Governance Council of the International Cerebral Palsy Genomics Consortium(ICPGC). His most recent work has focused on the discovery of large-scale, highly-penetrant
rare variation in children with CP, and the delineation of the extent to which genetic andgenomic changes contribute to this disorder.
Dr. Wintle holds a PhD in Molecular and Medical Genetics from the University ofToronto, during which he characterized the human immunoglobulin heavy chain gene cluster,as part of international efforts supporting chromosome 14 mapping for the Human Genome
Project. He completed his postdoctoral training at the Centre for Addiction and Mental Healthin Toronto, studying the molecular neurobiology of dopamine signalling in the modelorganism, the nematode C. elegans. Following this, he worked in two related biotechnology
startup companies, in a variety of R&D and Operations roles, mainly focused on the complex
genetics of autoimmune and inflammatory disorders. Since 2006, he has been with TheCentre for Applied Genomics (TCAG), a genome centre located within the Research Instituteof The Hospital for Sick Children in Toronto, Canada, where he serves as Assistant Director
and a member of its Scientific Management. TCAG is a Genomics Technology Platform ofGenome Canada, and a founding member of Canada’s Genomics Enterprise, a nationallyfunded, pan-Canadian genome sequencing network, and is affiliated with the University ofToronto. A major focus of work at TCAG is in developing approaches to identify and interpret
structural variation within whole genome sequence (WGS) data. Dr. Wintle has also acted asa consultant to a wide variety of private- and public-sector biotechnology, market research,and healthcare organizations.