Mandrake: visualizing microbial population structure by embedding millions of genomes into a low-dimensional representation

Author:

Lees John A.12,Tonkin-Hill Gerry3,Yang Zhirong45,Corander Jukka367ORCID

Affiliation:

1. MRC Centre for Global Infectious Disease Analysis, School of Public Health, Imperial College London, London W2 1PG, UK

2. European Molecular Biology Laboratory, European Bioinformatics Institute EMBL-EBI, Hinxton CB10 1SD, UK

3. Department of Biostatistics, University of Oslo, 0317 Oslo, Norway

4. Department of Computer Science, Norwegian University of Science and Technology, 7491 Trondheim, Norway

5. Aalto University, 02150 Espoo, Finland

6. Parasites and Microbes, Wellcome Sanger Institute, Cambridge CB10 1SA, UK

7. Helsinki Institute for Information Technology HIIT, Department of Mathematics and Statistics, University of Helsinki, 00100 Helsinki, Finland

Abstract

In less than a decade, population genomics of microbes has progressed from the effort of sequencing dozens of strains to thousands, or even tens of thousands of strains in a single study. There are now hundreds of thousands of genomes available even for a single bacterial species, and the number of genomes is expected to continue to increase at an accelerated pace given the advances in sequencing technology and widespread genomic surveillance initiatives. This explosion of data calls for innovative methods to enable rapid exploration of the structure of a population based on different data modalities, such as multiple sequence alignments, assemblies and estimates of gene content across different genomes. Here, we present Mandrake, an efficient implementation of a dimensional reduction method tailored for the needs of large-scale population genomics. Mandrake is capable of visualizing population structure from millions of whole genomes, and we illustrate its usefulness with several datasets representing major pathogens. Our method is freely available both as an analysis pipeline (https://github.com/johnlees/mandrake) and as a browser-based interactive application (https://gtonkinhill.github.io/mandrake-web/).This article is part of a discussion meeting issue ‘Genomic population structures of microbial pathogens’.

Funder

Norges Forskningsråd

Medical Research Council

H2020 European Research Council

Publisher

The Royal Society

Subject

General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology

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