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A scalable, fully automated process for construction of sequence-ready human exome targeted capture libraries

Sheila Fisher1, Andrew Barry1, Justin Abreu1, Brian Minie1, Jillian Nolan1, Toni M Delorey1, Geneva Young1, Timothy J Fennell1, Alexander Allen1, Lauren Ambrogio1, Aaron M Berlin2, Brendan Blumenstiel3, Kristian Cibulskis3, Dennis Friedrich1, Ryan Johnson1, Frank Juhn4, Brian Reilly1, Ramy Shammas1, John Stalker1, Sean M Sykes2, Jon Thompson1, John Walsh1, Andrew Zimmer1, Zac Zwirko14, Stacey Gabriel2, Robert Nicol1 and Chad Nusbaum2*

Author Affiliations

1 Genome Sequencing Platform, Broad Institute of MIT and Harvard, 320 Charles Street, Cambridge, MA 02141, USA

2 Genome Sequencing and Analysis Program, Broad Institute of MIT and Harvard, 320 Charles Street, Cambridge, MA 02141, USA

3 Genetic Analysis Platform, Broad Institute of MIT and Harvard, 320 Charles Street, Cambridge, MA 02141, USA

4 Foundation Medicine, One Kendall Square, Suite B6501, Cambridge, MA 02139, USA

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Genome Biology 2011, 12:R1  doi:10.1186/gb-2011-12-1-r1

Published: 4 January 2011

Abstract

Genome targeting methods enable cost-effective capture of specific subsets of the genome for sequencing. We present here an automated, highly scalable method for carrying out the Solution Hybrid Selection capture approach that provides a dramatic increase in scale and throughput of sequence-ready libraries produced. Significant process improvements and a series of in-process quality control checkpoints are also added. These process improvements can also be used in a manual version of the protocol.