A strategy for building and using a human reference pangenome

Bastien Llamas; Giuseppe Narzisi; Valerie Schneider; Peter A Audano; Evan Biederstedt; Lon Blauvelt; Peter Bradbury; Xian Chang; Chen-Shan Chin; Arkarachai Fungtammasan; Wayne E Clarke; Alan Cleary; Jana Ebler; Jordan Eizenga; Jonas A Sibbesen; Charles J Markello; Erik Garrison; Shilpa Garg; Glenn Hickey; Gerard R Lazo; Michael F Lin; Medhat Mahmoud; Tobias Marschall; Ilia Minkin; Jean Monlong; Rajeeva L Musunuri; Sagayamary Sagayaradj; Adam M Novak; Mikko Rautiainen; Allison Regier; Fritz J Sedlazeck; Jouni Siren; Yassine Souilmi; Justin Wagner; Travis Wrightsman; Toshiyuki T Yokoyama; Qiandong Zeng; Justin M Zook; Benedict Paten; Ben Busby

doi:10.12688/f1000research.19630.2

A strategy for building and using a human reference pangenome

F1000Res. 2019 Oct 14:8:1751. doi: 10.12688/f1000research.19630.2. eCollection 2019.

Authors

Bastien Llamas^#¹, Giuseppe Narzisi^#², Valerie Schneider^#³, Peter A Audano⁴, Evan Biederstedt^{5

6}, Lon Blauvelt⁷, Peter Bradbury⁸, Xian Chang⁷, Chen-Shan Chin⁹, Arkarachai Fungtammasan⁹, Wayne E Clarke², Alan Cleary¹⁰, Jana Ebler¹¹, Jordan Eizenga⁷, Jonas A Sibbesen⁷, Charles J Markello⁷, Erik Garrison⁷, Shilpa Garg¹², Glenn Hickey⁷, Gerard R Lazo¹³, Michael F Lin¹⁴, Medhat Mahmoud¹⁵, Tobias Marschall¹¹, Ilia Minkin¹⁶, Jean Monlong⁷, Rajeeva L Musunuri², Sagayamary Sagayaradj^{17

18}, Adam M Novak⁷, Mikko Rautiainen¹¹, Allison Regier¹⁹, Fritz J Sedlazeck¹⁵, Jouni Siren⁷, Yassine Souilmi¹, Justin Wagner²⁰, Travis Wrightsman²¹, Toshiyuki T Yokoyama²², Qiandong Zeng²³, Justin M Zook²⁰, Benedict Paten⁷, Ben Busby³

Affiliations

¹ Australian Centre for Ancient DNA, School of Biological Sciences, Environment Institute, The University of Adelaide, Adelaide, South Australia, 5005, Australia.
² New York Genome Center, New York, NY, 10013, USA.
³ National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, 20894, USA.
⁴ Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, 98195, USA.
⁵ Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
⁶ Department of Biomedical Informatics, Harvard Medical School, Boston, MA, 02215, USA.
⁷ Genomics Institute, University of California, Santa Cruz, Santa Cruz, CA, 95064, USA.
⁸ Robert W. Holley Center, USDA-ARS, Ithaca, NY, 14853, USA.
⁹ DNAnexus, Mountain View, CA, 94040, USA.
¹⁰ National Center for Genome Resources 87505, Santa Fe, NM, 87505, USA.
¹¹ Max Planck Institute for Informatics, Saarbrücken, Germany.
¹² Department of Genetics, Harvard Medical School, Boston, MA, 02115, USA.
¹³ Western Regional Research Center, USDA-ARS, Albany, CA, 94710-1105, USA.
¹⁴ mlin.net LLC, San Jose, CA, 95113, USA.
¹⁵ Human Genome Sequencing Center, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston TX, TX, 77030, USA.
¹⁶ Department of Computer Science and Engineering, The Pennsylvania State University, University Park, PA, 16802, USA.
¹⁷ Genome Center, University of California, Davis, Davis, CA, USA.
¹⁸ BASF, West Sacramento, CA, USA.
¹⁹ McDonnell Genome Institute, Washington University in St Louis, St Louis, MO, 63108, USA.
²⁰ Material Measurement Laboratory, National Institute of Standards and Technology, Gaithersburg, MD, 20899, USA.
²¹ Section of Plant Breeding and Genetics, Cornell University, Ithaca, NY, 14853, USA.
²² Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba, Japan.
²³ Laboratory Corporation of America Holdings, Westborough, MA, 01581, USA.

^# Contributed equally.

Abstract

In March 2019, 45 scientists and software engineers from around the world converged at the University of California, Santa Cruz for the first pangenomics codeathon. The purpose of the meeting was to propose technical specifications and standards for a usable human pangenome as well as to build relevant tools for genome graph infrastructures. During the meeting, the group held several intense and productive discussions covering a diverse set of topics, including advantages of graph genomes over a linear reference representation, design of new methods that can leverage graph-based data structures, and novel visualization and annotation approaches for pangenomes. Additionally, the participants self-organized themselves into teams that worked intensely over a three-day period to build a set of pipelines and tools for specific pangenomic applications. A summary of the questions raised and the tools developed are reported in this manuscript.

Keywords: Graph Genome; Hackathon; Pangenome; RNAseq; Structural Variant.

Abstract

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