High-throughput automated microfluidic sample preparation for accurate microbial genomics
Abstract
Low-cost shotgun DNA sequencing is transforming the microbial sciences. Sequencing instruments are so effective that sample preparation is now the key limiting factor. Here, we introduce a microfluidic sample preparation platform that integrates the key steps in cells to sequence library sample preparation for up to 96 samples and reduces DNA input requirements 100-fold while maintaining or improving data quality. The general-purpose microarchitecture we demonstrate supports workflows with arbitrary numbers of reaction and clean-up or capture steps. By reducing the sample quantity requirements, we enabled low-input (B10,000 cells) whole-genome shotgun (WGS) sequencing of Mycobacterium tuberculosis and soil micro-colonies with superior results. We also leveraged the enhanced throughput to sequence B400 clinical Pseudomonas aeruginosa libraries and demonstrate excellent single-nucleotide polymorphism detection performance that explained phenotypically observed antibiotic resistance. Fully-integrated lab-on-chip sample preparation overcomes technical barriers to enable broader deployment of genomics across many basic research and translational applications.
- Authors:
-
- The Broad Inst. of MIT and Harvard, Cambridge, MA (United States); Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States). Dept. of Biological Engineering
- The Broad Inst. of MIT and Harvard, Cambridge, MA (United States); Univ. of Cambridge (United Kingdom). Dept. of Biochemistry
- The Broad Inst. of MIT and Harvard, Cambridge, MA (United States); Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States). Dept. of Physics
- The Broad Inst. of MIT and Harvard, Cambridge, MA (United States); Aalto Univ., Otaniemi (Finland). Dept. of Computer Science
- The Broad Inst. of MIT and Harvard, Cambridge, MA (United States); Massachusetts General Hospital, Boston, MA (United States). Division of Infectious Diseases
- Northeastern Univ., Boston, MA (United States). Dept. of Biology
- The Broad Inst. of MIT and Harvard, Cambridge, MA (United States)
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC)
- OSTI Identifier:
- 1623869
- Grant/Contract Number:
- AC02-05CH11231
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Nature Communications
- Additional Journal Information:
- Journal Volume: 8; Journal Issue: 1; Journal ID: ISSN 2041-1723
- Publisher:
- Nature Publishing Group
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; Science & Technology - Other Topics
Citation Formats
Kim, Soohong, De Jonghe, Joachim, Kulesa, Anthony B., Feldman, David, Vatanen, Tommi, Bhattacharyya, Roby P., Berdy, Brittany, Gomez, James, Nolan, Jill, Epstein, Slava, and Blainey, Paul C. High-throughput automated microfluidic sample preparation for accurate microbial genomics. United States: N. p., 2017.
Web. doi:10.1038/ncomms13919.
Kim, Soohong, De Jonghe, Joachim, Kulesa, Anthony B., Feldman, David, Vatanen, Tommi, Bhattacharyya, Roby P., Berdy, Brittany, Gomez, James, Nolan, Jill, Epstein, Slava, & Blainey, Paul C. High-throughput automated microfluidic sample preparation for accurate microbial genomics. United States. https://doi.org/10.1038/ncomms13919
Kim, Soohong, De Jonghe, Joachim, Kulesa, Anthony B., Feldman, David, Vatanen, Tommi, Bhattacharyya, Roby P., Berdy, Brittany, Gomez, James, Nolan, Jill, Epstein, Slava, and Blainey, Paul C. Fri .
"High-throughput automated microfluidic sample preparation for accurate microbial genomics". United States. https://doi.org/10.1038/ncomms13919. https://www.osti.gov/servlets/purl/1623869.
@article{osti_1623869,
title = {High-throughput automated microfluidic sample preparation for accurate microbial genomics},
author = {Kim, Soohong and De Jonghe, Joachim and Kulesa, Anthony B. and Feldman, David and Vatanen, Tommi and Bhattacharyya, Roby P. and Berdy, Brittany and Gomez, James and Nolan, Jill and Epstein, Slava and Blainey, Paul C.},
abstractNote = {Low-cost shotgun DNA sequencing is transforming the microbial sciences. Sequencing instruments are so effective that sample preparation is now the key limiting factor. Here, we introduce a microfluidic sample preparation platform that integrates the key steps in cells to sequence library sample preparation for up to 96 samples and reduces DNA input requirements 100-fold while maintaining or improving data quality. The general-purpose microarchitecture we demonstrate supports workflows with arbitrary numbers of reaction and clean-up or capture steps. By reducing the sample quantity requirements, we enabled low-input (B10,000 cells) whole-genome shotgun (WGS) sequencing of Mycobacterium tuberculosis and soil micro-colonies with superior results. We also leveraged the enhanced throughput to sequence B400 clinical Pseudomonas aeruginosa libraries and demonstrate excellent single-nucleotide polymorphism detection performance that explained phenotypically observed antibiotic resistance. Fully-integrated lab-on-chip sample preparation overcomes technical barriers to enable broader deployment of genomics across many basic research and translational applications.},
doi = {10.1038/ncomms13919},
journal = {Nature Communications},
number = 1,
volume = 8,
place = {United States},
year = {Fri Jan 27 00:00:00 EST 2017},
month = {Fri Jan 27 00:00:00 EST 2017}
}
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