Development and deployment of clinical genome sequencing using a cloud-based platform

Lynette Lau, Edward Higginbotham, Wilson Sung, Venuja Sriretnakumar, Meredith Curtis, Caitlin Chisholm, Meredith Gillespie, Anna Pan, Sean Kim, Sean Simko, E. Magda Price, Marianne Eliou, Anna Szuto, Michelle Axford, Martin Somerville, Kym Boycott, Jean McGowan-Jordan, Melaine Beaulieu Bergeron, James Stavropoulos, Lijia Huang, Christian Marshall

Linking human phenotype ontology (HPO) terms and pedigree information to genomic analysis platforms through PhenoTips, CHEO and SickKids built and validated an end-to-end, cloud-based, and easily updated solution to deliver clinical exome and genome sequencing for Ontarians with a suspected rare disease.

Care4Rare Canada: Outcomes from a decade of network science for rare disease gene discovery

Kym M. Boycott, Taila Hartley, Kristin D. Kernohan, David A. Dyment, Heather Howley, A. Micheil Innes, Francois P. Bernier, Michael Brudno, Care4Rare Canada Consortium

Using PhenoTips to support the collection of computer-readable phenotypic data and facilitate the data transfer first-step entry into the Care4Rare discovery pipeline, the Care4Rare Consortium used 'omic technologies to identify the molecular cause of unsolved rare diseases with a 34% diagnostic yield and significant contributions to rare disease research, including the implementation of genome-wide sequencing as a publicly funded test for rare disease diagnosis in Canada.

The performance of genome sequencing as a first-tier test for neurodevelopmental disorders

Bart P. G. H. van der Sanden, Gaby Schobers, Jordi Corominas Galbany, David A. Koolen, Margje Sinnema, Jeroen van Reeuwijk, Connie T. R. M. Stumpel, Tjitske Kleefstra, Bert B. A. de Vries, Martina Ruiterkamp-Versteeg, Nico Leijsten, Michael Kwint, Ronny Derks, Hilde Swinkels, Amber den Ouden, Rolph Pfundt, Tuula Rinne, Nicole de Leeuw, Alexander P. Stegmann, Servi J. Stevens, Arthur van den Wijngaard, Han G. Brunner, Helger G. Yntema, Christian Gilissen, Marcel R. Nelen, Lisenka E. L. M. Vissers

Using PhenoTips to collect HPO-coded phenotypic information from electronic health records, diagnostic yield for 150 patients with neurodevelopmental disorders and their parents was evaluated with genome sequencing and the current standard of care, finding similar yield but improved efficiency of genome sequencing as a first-tier test for neurodevelopmental disorders.

Genomic answers for children: Dynamic analyses of >1000 pediatric rare disease genomes

Ana SA Cohen, Emily G Farrow, Ahmed T Abdelmoity, Joseph T Alaimo, Shivarajan M Amudhavalli, John T Anderson, Lalit Bansal, Lauren Bartik, Primo Baybayan, Bradley Belden, Courtney D Berrios, Rebecca L Biswell, Pawel Buczkowicz, Orion Buske, Shreyasee Chakraborty, Warren A Cheung, Keith A Coffman, Ashley M Cooper, Laura A Cross, Thomas Curran, Thuy Tien T Dang, Mary M Elfrink, Kendra L Engleman, Erin D Fecske, Cynthia Fieser, Keely Fitzgerald, Emily A Fleming, Randi N Gadea, Jennifer L Gannon, Rose N Gelineau-Morel, Margaret Gibson, Jeffrey Goldstein, Elin Grundberg, Kelsee Halpin, Brian S Harvey, Bryce A Heese, Wendy Hein, Suzanne M Herd, Susan S Hughes, Mohammed Ilyas, Jill Jacobson, Janda L Jenkins, Shao Jiang, Jeffrey J Johnston, Kathryn Keeler, Jonas Korlach, Jennifer Kussmann, Christine Lambert, Caitlin Lawson, Jean-Baptiste Le Pichon, Steve Leeder, Vicki C Little, Daniel A Louiselle, Michael Lypka, Brittany D McDonald, Neil Miller, Ann Modrcin, Annapoorna Nair, Shelby H Neal, Christopher M Oermann, Donna M Pacicca, Kailash Pawar, Nyshele L Posey, Nigel Price, Laura MB Puckett, Julio F Quezada, Nikita Raje, William J Rowell, Eric T Rush, Venkatesh Sampath, Carol J Saunders, Caitlin Schwager, Richard M Schwend, Elizabeth Shaffer, Craig Smail, Sarah Soden, Meghan E Strenk, Bonnie R Sullivan, Brooke R Sweeney, Jade B Tam-Williams, Adam M Walter, Holly Welsh, Aaron M Wenger, Laurel K Willig, Yun Yan, Scott T Younger, Dihong Zhou, Tricia N Zion, Isabelle Thiffault, Tomi Pastinen

Using PhenoTips to store structured phenotypes, prioritized variants and pedigrees, 960 families with suspected genetic disorders received comprehensive diagnostic and candidate analyses through the Genomic Answers for Kids (GA4K) program.

Genomics4RD: An integrated platform to share Canadian deep-phenotype and multiomic data for international rare disease gene discovery

Hannah G. Driver, Taila Hartley, E. Magda Price, Andrei L. Turinsky, Orion J. Buske, Matthew Osmond, Arun K. Ramani, Emily Kirby, Kristin D. Kernohan, Madeline Couse, Hillary Elrick, Kevin Lu, Pouria Mashouri, Aarthi Mohan, Delvin So, Conor Klamann, Hannah G. B. H. Le, Andrea Herscovich, Christian R. Marshall, Andrew Statia, Care4Rare Canada Consortium, Bartha M. Knoppers, Michael Brudno, Kym M. Boycott

Genomics4RD is a platform to share Canadian phenotypic and multiomic data, collected and standardized via PhenoTips, between researchers for the purpose of discovering the mechanisms that cause rare disease.

PhenomeCentral: 7 years of rare disease matchmaking

Matthew Osmond, Taila Hartley, Brittney Johnstone, Sasha Andjic, Marta Girdea, Meredith Gillespie, Orion Buske, Sergiu Dumitriu, Veronika Koltunova, Arun Ramani, Kym M Boycott, Michael Brudno

Over the past 7 years PhenomeCentral, a rare disease data repository facilitating matchmaking and built on PhenoTips technology, has resulted in 60,000 matches and multiple gene discoveries. Read more about where PhenomeCentral is today and its potential future applications.

Genome Sequencing as a Diagnostic Test in Children With Unexplained Medical Complexity.

Gregory Costain, Susan Walker, Maria Marano, Danielle Veenma, Meaghan Snell, Meredith Curtis, Stephanie Luca, Jason Buera, Danielle Arje, Miriam S. Reuter, Bhooma Thiruvahindrapuram, Brett Trost, Wilson W. L. Sung, Ryan K. C. Yuen, David Chitayat, Roberto Mendoza-Londono, D. James Stavropoulos, Stephen W. Scherer, Christian R. Marshall, Ronald D. Cohn, Eyal Cohen, Julia Orkin, M. Stephen Meyn, Robin Z. Hayeems

Using PhenoTips to capture family history and HPO-coded phenotype data, 138 children with medical complexity and prior negative genetic testing results received genome sequencing resulting in a new diagnosis for 31% of patients.

The Cardiac Genome Clinic: implementing genome sequencing in pediatric heart disease.

Miriam S. Reuter, Rajiv R. Chaturvedi, Eriskay Liston, Roozbeh Manshaei, Ritu B. Aul, Sarah Bowdin, Iris Cohn, Meredith Curtis, Priya Dhir, Robin Z. Hayeems, S. Mohsen Hosseini, Reem Khan, Linh G. Ly, Christian R. Marshall, Luc Mertens, John B. A. Okello, Sergio L. Pereira, Akshaya Raajkumar, Mike Seed, Bhooma Thiruvahindrapuram, Stephen W. Scherer, Raymond H. Kim, Rebekah K. Jobling

Using PhenoTips to capture HPO-coded phenotype data, genome sequencing data of 111 families with cardiac lesions were analyzed for rare, disease-associated variation, demonstrating the diagnostic and scientific value of genome sequencing in pediatric heart disease, anticipating its role as a first-tier diagnostic test.