OpenPBTA: The Open Pediatric Brain Tumor Atlas

Joshua A Shapiro; Krutika S Gaonkar; Stephanie J Spielman; Candace L Savonen; Chante J Bethell; Run Jin; Komal S Rathi; Yuankun Zhu; Laura E Egolf; Bailey K Farrow; Daniel P Miller; Yang Yang; Tejaswi Koganti; Nighat Noureen; Mateusz P Koptyra; Nhat Duong; Mariarita Santi; Jung Kim; Shannon Robins; Phillip B Storm; Stephen C Mack; Jena V Lilly; Hongbo M Xie; Payal Jain; Pichai Raman; Brian R Rood; Rishi R Lulla; Javad Nazarian; Adam A Kraya; Zalman Vaksman; Allison P Heath; Cassie Kline; Laura Scolaro; Angela N Viaene; Xiaoyan Huang; Gregory P Way; Steven M Foltz; Bo Zhang; Anna R Poetsch; Sabine Mueller; Brian M Ennis; Michael Prados; Sharon J Diskin; Siyuan Zheng; Yiran Guo; Shrivats Kannan; Angela J Waanders; Ashley S Margol; Meen Chul Kim; Derek Hanson; Nicholas Van Kuren; Jessica Wong; Rebecca S Kaufman; Noel Coleman; Christopher Blackden; Kristina A Cole; Jennifer L Mason; Peter J Madsen; Carl J Koschmann; Douglas R Stewart; Eric Wafula; Miguel A Brown; Adam C Resnick; Casey S Greene; Jo Lynne Rokita; Jaclyn N Taroni; Children’s Brain Tumor Network; Pacific Pediatric Neuro-Oncology Consortium

doi:10.1016/j.xgen.2023.100340

OpenPBTA: The Open Pediatric Brain Tumor Atlas

Cell Genom. 2023 May 31;3(7):100340. doi: 10.1016/j.xgen.2023.100340. eCollection 2023 Jul 12.

Authors

Joshua A Shapiro¹, Krutika S Gaonkar^{2

3

4}, Stephanie J Spielman^{1

5}, Candace L Savonen¹, Chante J Bethell¹, Run Jin^{2

3}, Komal S Rathi^{2

4}, Yuankun Zhu^{2

3}, Laura E Egolf^{6

7}, Bailey K Farrow^{2

3}, Daniel P Miller^{2

3}, Yang Yang⁸, Tejaswi Koganti^{2

3}, Nighat Noureen⁹, Mateusz P Koptyra^{2

3}, Nhat Duong⁴, Mariarita Santi^{10

11}, Jung Kim¹², Shannon Robins^{2

3}, Phillip B Storm^{2

3}, Stephen C Mack¹³, Jena V Lilly^{2

3}, Hongbo M Xie⁴, Payal Jain^{2

3}, Pichai Raman^{2

4}, Brian R Rood^{14

15}, Rishi R Lulla^{16

17}, Javad Nazarian^{14

15

18}, Adam A Kraya^{2

3}, Zalman Vaksman⁷, Allison P Heath^{2

3}, Cassie Kline⁷, Laura Scolaro⁷, Angela N Viaene^{10

11}, Xiaoyan Huang^{2

3}, Gregory P Way¹⁹, Steven M Foltz^{1

20}, Bo Zhang^{2

3}, Anna R Poetsch^{21

22}, Sabine Mueller²³, Brian M Ennis^{2

3}, Michael Prados²⁴, Sharon J Diskin^{7

25}, Siyuan Zheng⁹, Yiran Guo², Shrivats Kannan^{2

3}, Angela J Waanders^{26

27}, Ashley S Margol^{28

29}, Meen Chul Kim^{2

3}, Derek Hanson^{30

31}, Nicholas Van Kuren^{2

3}, Jessica Wong^{2

3}, Rebecca S Kaufman^{4

7}, Noel Coleman^{2

3}, Christopher Blackden^{2

3}, Kristina A Cole^{7

25

32}, Jennifer L Mason^{2

3}, Peter J Madsen^{2

3}, Carl J Koschmann^{33

34}, Douglas R Stewart¹², Eric Wafula⁴, Miguel A Brown^{2

3}, Adam C Resnick^{2

3}, Casey S Greene^{1

19

35}, Jo Lynne Rokita^{2

3

4}, Jaclyn N Taroni¹; Children’s Brain Tumor Network; Pacific Pediatric Neuro-Oncology Consortium

Affiliations

¹ Childhood Cancer Data Lab, Alex's Lemonade Stand Foundation, Bala Cynwyd, PA 19004, USA.
² Center for Data-Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
³ Division of Neurosurgery, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
⁴ Department of Bioinformatics and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
⁵ Rowan University, Glassboro, NJ 08028, USA.
⁶ Cell and Molecular Biology Graduate Group, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
⁷ Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
⁸ Ben May Department for Cancer Research, University of Chicago, Chicago, IL 60637, USA.
⁹ Greehey Children's Cancer Research Institute, UT Health San Antonio, San Antonio, TX 78229, USA.
¹⁰ Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
¹¹ Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
¹² Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20850, USA.
¹³ Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
¹⁴ Children's National Research Institute, Washington, DC 20012, USA.
¹⁵ George Washington University School of Medicine and Health Sciences, Washington, DC 20052, USA.
¹⁶ Division of Hematology/Oncology, Hasbro Children's Hospital, Providence, RI 02903, USA.
¹⁷ Department of Pediatrics, The Warren Alpert School of Brown University, Providence, RI 02912, USA.
¹⁸ Department of Pediatrics, University of Zurich, Zurich, Switzerland.
¹⁹ Department of Biomedical Informatics, University of Colorado School of Medicine, Aurora, CO 80045, USA.
²⁰ Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA.
²¹ Biotechnology Center, Technical University Dresden, Dresden, Germany.
²² National Center for Tumor Diseases, Dresden, Germany.
²³ Department of Neurology, Neurosurgery and Pediatrics, University of California, San Francisco, San Francisco, CA 94115, USA.
²⁴ University of California, San Francisco, San Francisco, CA 94115, USA.
²⁵ Department of Pediatrics, University of Pennsylvania, Philadelphia, PA 19104, USA.
²⁶ Division of Hematology, Oncology, Neuro-Oncology, and Stem Cell Transplant, Ann & Robert H Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA.
²⁷ Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
²⁸ Division of Hematology and Oncology, Children's Hospital of Los Angeles, Los Angeles, CA 90027, USA.
²⁹ Department of Pediatrics, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033, USA.
³⁰ Hackensack Meridian School of Medicine, Nutley, NJ 07110, USA.
³¹ Hackensack University Medical Center, Hackensack, NJ 07601, USA.
³² Abramson Family Cancer Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
³³ Department of Pediatrics, University of Michigan Health, Ann Arbor, MI 48105, USA.
³⁴ Pediatric Hematology Oncology, Mott Children's Hospital, Ann Arbor, MI 48109, USA.
³⁵ Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Abstract

Pediatric brain and spinal cancers are collectively the leading disease-related cause of death in children; thus, we urgently need curative therapeutic strategies for these tumors. To accelerate such discoveries, the Children's Brain Tumor Network (CBTN) and Pacific Pediatric Neuro-Oncology Consortium (PNOC) created a systematic process for tumor biobanking, model generation, and sequencing with immediate access to harmonized data. We leverage these data to establish OpenPBTA, an open collaborative project with over 40 scalable analysis modules that genomically characterize 1,074 pediatric brain tumors. Transcriptomic classification reveals universal TP53 dysregulation in mismatch repair-deficient hypermutant high-grade gliomas and TP53 loss as a significant marker for poor overall survival in ependymomas and H3 K28-mutant diffuse midline gliomas. Already being actively applied to other pediatric cancers and PNOC molecular tumor board decision-making, OpenPBTA is an invaluable resource to the pediatric oncology community.

Keywords: brain tumors; classification; open science; pediatric cancer; reproducibility; somatic variation; tumor atlas.

Grants and funding

R01 NS119231/NS/NINDS NIH HHS/United States