A strategy for building and using a human reference pangenome

Authors: LLAMAS, BASTIEN - University Of Adelaide; NARZISI, GIUSEPPE - New York Genome Center; SCHNEIDER, VALERIE - National Institutes Of Health (NIH); AUDANO, PETER - University Of Washington Medical School; BIEDERSTEDT, EVAN - Memorial Sloan Kettering; BLAUVELT, LON - University Of California Santa Cruz; Bradbury, Peter; CHANG, XIN - University Of California Santa Cruz; CHIN, CHEN-SHAN - Dnanexus; FUNGTAMMASAN, ARKARACHAI - Dnanexus; CLARKE, WAYNE - New York Genome Center; CLEARY, ALAN - National Center For Genome Resources; EBLER, JANA - Max Planck Institute For Informatics; EIZENGA, JORDAN - University Of California Santa Cruz; SIBBESEN, JONAS - University Of California Santa Cruz; MARKELLO, CHARLES - University Of California Santa Cruz; GARRISON, ERIK - University Of California Santa Cruz; Lazo, Gerard; LIN, MICHAEL - Dnanexus; MAHMOUD, MEDHAT - Baylor College Of Medicine; MARSCHALL, TOBIAS - Saarland University; MINKIN, LLIA - Pennsylvania State University; MONLONG, JEAN - University Of California Santa Cruz; MUSUNURI, RAJEEVA - New York Genome Center; SAGAYARADJ, SAGAYAMARY - Uc Davis Medical Center; NOVAK, ADAM - University Of California Santa Cruz; RAUTIAINEN, MIKKO - Max Planck Institute For Informatics; REGIER, ALLISON - Washington University; SEDLAZECK, FRITZ - Baylor College Of Medicine; SIREN, JOUNI - University Of California Santa Cruz; SOUILMI, YASSINE - University Of Adelaide; SOUILMI, YASSINE - National Institute Of Standards And Technology; WRIGHTSMAN, TRAVIS - Cornell University; YOKOYAMA, TOSHIYUKI - University Of Tokyo; ZENG, QIANDONG - Labcorp; ZOOK, JUSTIN - National Institute Of Standards And Technology; PATEN, BENEDICT - University Of California Santa Cruz; BUSBY, BEN - National Institutes Of Health (NIH)

Submitted to: F1000Research
Publication Type: Other
Publication Acceptance Date: 10/14/2019
Publication Date: 10/14/2019
Citation: Llamas, B., Narzisi, G., Schneider, V., Audano, P.A., Biederstedt, E., Blauvelt, L., Bradbury, P., Chang, X., Chin, C., Fungtammasan, A., Clarke, W.E., Cleary, A., Ebler, J., Eizenga, J.M., Sibbesen, J.A., Markello, C.J., Garrison, E., Lazo, G.R., Lin, M.F., Mahmoud, M., Marschall, T., Minkin, L., Monlong, J., Musunuri, R.L., Sagayaradj, S., Novak, A.M., Rautiainen, M., Regier, A., Sedlazeck, F.J., Siren, J., Souilmi, Y., Souilmi, Y., Wrightsman, T., Yokoyama, T., Zeng, Q., Zook, J.M., Paten, B., Busby, B. 2019. A strategy for building and using a human reference pangenome. F1000Research. 8:1751. https://doi.org/10.12688/f1000research.19630.1.
DOI: https://doi.org/10.12688/f1000research.19630.1

Interpretive Summary: In March 2019, 45 scientists and software engineers from around the world converged at the University of California, Santa Cruz for the first pangenomics hackathon. The purpose of the meeting was to propose technical specifications and standards for a usable human pangenome as well as to write software tools. Although, a high-quality human reference genome exists that represents a single individual, DNA of all humans contain a lot of sequence variation and whole DNA segments not present in the reference genome. A representation of the genomic variation present in all individuals of a species is called a pangenome. Some software tools already exist to create and use a graphical representation of a pangenome. The pangenomics hackathon assembled experts in the field who developed new software and organized test data sets with the goal of creating a reference human pangenome. Some participants investigated the application of these methods to other species such as corn and wheat.

Technical 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 hackathon. 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