Pediatric Cancer Variant Pathogenicity Information Exchange (PeCanPIE): a cloud-based platform for curating and classifying germline variants
- Michael N. Edmonson1,11,
- Aman N. Patel1,11,
- Dale J. Hedges1,
- Zhaoming Wang1,
- Evadnie Rampersaud1,
- Chimene A. Kesserwan2,
- Xin Zhou1,
- Yanling Liu1,
- Scott Newman1,
- Michael C. Rusch1,
- Clay L. McLeod1,
- Mark R. Wilkinson1,
- Stephen V. Rice1,
- Thierry Soussi3,4,5,
- J. Paul Taylor6,7,
- Michael Benatar8,
- Jared B. Becksfort1,
- Kim E. Nichols2,
- Leslie L. Robison9,
- James R. Downing10 and
- Jinghui Zhang1
- 1Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA;
- 2Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA;
- 3Sorbonne Université, UPMC Univ Paris 06, F-75005 Paris, France;
- 4Department of Oncology-Pathology, Cancer Center Karolinska (CCK), Karolinska Institutet, 171 64 Stockholm, Sweden;
- 5INSERM, U1138, Équipe 11, Centre de Recherche des Cordeliers, 75006 Paris, France;
- 6Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA;
- 7Department of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA;
- 8Department of Neurology, University of Miami, Miami, Florida 33136, USA;
- 9Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA;
- 10Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA
-
↵11 These authors contributed equally to this work.
Abstract
Variant interpretation in the era of massively parallel sequencing is challenging. Although many resources and guidelines are available to assist with this task, few integrated end-to-end tools exist. Here, we present the Pediatric Cancer Variant Pathogenicity Information Exchange (PeCanPIE), a web- and cloud-based platform for annotation, identification, and classification of variations in known or putative disease genes. Starting from a set of variants in variant call format (VCF), variants are annotated, ranked by putative pathogenicity, and presented for formal classification using a decision-support interface based on published guidelines from the American College of Medical Genetics and Genomics (ACMG). The system can accept files containing millions of variants and handle single-nucleotide variants (SNVs), simple insertions/deletions (indels), multiple-nucleotide variants (MNVs), and complex substitutions. PeCanPIE has been applied to classify variant pathogenicity in cancer predisposition genes in two large-scale investigations involving >4000 pediatric cancer patients and serves as a repository for the expert-reviewed results. PeCanPIE was originally developed for pediatric cancer but can be easily extended for use for nonpediatric cancers and noncancer genetic diseases. Although PeCanPIE's web-based interface was designed to be accessible to non-bioinformaticians, its back-end pipelines may also be run independently on the cloud, facilitating direct integration and broader adoption. PeCanPIE is publicly available and free for research use.
Footnotes
-
[Supplemental material is available for this article.]
-
Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.250357.119.
-
Freely available online through the Genome Research Open Access option.
- Received March 13, 2019.
- Accepted July 23, 2019.
This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.