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Hybrid selection for sequencing pathogen genomes from clinical samples

Alexandre Melnikov1, Kevin Galinsky1, Peter Rogov1, Timothy Fennell1, Daria Van Tyne2, Carsten Russ1, Rachel Daniels1, Kayla G Barnes2, James Bochicchio1, Daouda Ndiaye3, Papa D Sene3, Dyann F Wirth2, Chad Nusbaum1, Sarah K Volkman2, Bruce W Birren1, Andreas Gnirke1 and Daniel E Neafsey1*

Author Affiliations

1 Genome Sequencing and Analysis Program, Broad Institute, 7 Cambridge Center, Cambridge, MA 02142, USA

2 Department of Immunology and Infectious Disease, Harvard School of Public Health, 665 Huntington Ave, Boston, MA 02115, USA

3 Faculty of Medicine and Pharmacy, Cheikh Anta Diop University, BP 7325, Dakar, Senegal

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Genome Biology 2011, 12:R73 doi:10.1186/gb-2011-12-8-r73

Published: 11 August 2011

Abstract

We have adapted a solution hybrid selection protocol to enrich pathogen DNA in clinical samples dominated by human genetic material. Using mock mixtures of human and Plasmodium falciparum malaria parasite DNA as well as clinical samples from infected patients, we demonstrate an average of approximately 40-fold enrichment of parasite DNA after hybrid selection. This approach will enable efficient genome sequencing of pathogens from clinical samples, as well as sequencing of endosymbiotic organisms such as Wolbachia that live inside diverse metazoan phyla.