Computational pan-genomics: status, promises and challenges

• Published in: Briefings in bioinformatics Vol. 19; no. 1; pp. 118 - 135
• Main Authors: Marschall, Tobias, Marz, Manja, Abeel, Thomas, Dijkstra, Louis, Dutilh, Bas E, Ghaffaari, Ali, Kersey, Paul, Kloosterman, Wigard P, Mäkinen, Veli, Novak, Adam M, Paten, Benedict, Porubsky, David, Rivals, Eric, Alkan, Can, Baaijens, Jasmijn A, Paul I W De Bakker, Boeva, Valentina, Bonnal, Raoul J P, Chiaromonte, Francesca, Chikhi, Rayan, Ciccarelli, Francesca D, Cijvat, Robin, Datema, Erwin, Van Duijn, Cornelia M, Eichler, Evan E, Ernst, Corinna, Eskin, Eleazar, Garrison, Erik, El-Kebir, Mohammed, Klau, Gunnar W, Korbel, Jan O, Eric-Wubbo Lameijer, Langmead, Benjamin, Martin, Marcel, Medvedev, Paul, Mu, John C, Neerincx, Pieter, Ouwens, Klaasjan, Peterlongo, Pierre, Pisanti, Nadia, Rahmann, Sven, Raphael, Ben, Reinert, Knut, de Ridder, Dick, de Ridder, Jeroen, Schlesner, Matthias, Schulz-Trieglaff, Ole, Sanders, Ashley D, Sheikhizadeh, Siavash, Shneider, Carl, Smit, Sandra, Valenzuela, Daniel, Wang, Jiayin, Wessels, Lodewyk, Zhang, Ying, Guryev, Victor, Vandin, Fabio, Ye, Kai, Schönhuth, Alexander
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.01.2018; Oxford Publishing Limited (England); Oxford University Press (OUP)
• Subjects: Algorithms; Bioinformatica; Bioinformatics; Computational Biology - methods; computational methodology; Computer applications; Computer Science; data collection; data structures; Domains; EPS; Gene sequencing; Genetics; genome; Genome, Human; Genomes; Genomics; Genomics - methods; Graphical representations; graphs; haplotypes; Homo sapiens; human genetics; Humans; Microbiology; nucleotide sequences; Oncology; pan-genome; Plant breeding; read mapping; sequence graph; Software; virology; pan-genome; haplotypes; data structures; read mapping; sequence graph
• ISSN: 1467-5463; 1477-4054; 1477-4054
• DOI: 10.1093/bib/bbw089

Abstract Many disciplines, from human genetics and oncology to plant breeding, microbiology and virology, commonly face the challenge of analyzing rapidly increasing numbers of genomes. In case of Homo sapiens, the number of sequenced genomes will approach hundreds of thousands in the next few years. Simply scaling up established bioinformatics pipelines will not be sufficient for leveraging the full potential of such rich genomic data sets. Instead, novel, qualitatively different computational methods and paradigms are needed. We will witness the rapid extension of computational pan-genomics, a new sub-area of research in computational biology. In this article, we generalize existing definitions and understand a pan-genome as any collection of genomic sequences to be analyzed jointly or to be used as a reference. We examine already available approaches to construct and use pan-genomes, discuss the potential benefits of future technologies and methodologies and review open challenges from the vantage point of the above-mentioned biological disciplines. As a prominent example for a computational paradigm shift, we particularly highlight the transition from the representation of reference genomes as strings to representations as graphs. We outline how this and other challenges from different application domains translate into common computational problems, point out relevant bioinformatics techniques and identify open problems in computer science. With this review, we aim to increase awareness that a joint approach to computational pan-genomics can help address many of the problems currently faced in various domains.