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Title: Millstone: software for multiplex microbial genome analysis and engineering

Abstract

Inexpensive DNA sequencing and advances in genome editing have made computational analysis a major rate-limiting step in adaptive laboratory evolution and microbial genome engineering. Here, we describe Millstone, a web-based platform that automates genotype comparison and visualization for projects with up to hundreds of genomic samples. To enable iterative genome engineering, Millstone allows users to design oligonucleotide libraries and create successive versions of reference genomes. Millstone is open source and easily deployable to a cloud platform, local cluster, or desktop, making it a scalable solution for any lab.

Authors:
; ; ; ; ; ; ;
Publication Date:
Research Org.:
Harvard Univ., Boston, MA (United States). Harvard Medical School
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER)
Contributing Org.:
AWS Cloud Credits for Research Program
OSTI Identifier:
1618928
Alternate Identifier(s):
OSTI ID: 1371690
Grant/Contract Number:  
FG02-02ER63445
Resource Type:
Published Article
Journal Name:
Genome Biology (Online)
Additional Journal Information:
Journal Name: Genome Biology (Online) Journal Volume: 18 Journal Issue: 1; Journal ID: ISSN 1474-760X
Publisher:
Springer Science + Business Media
Country of Publication:
United Kingdom
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; Synthetic biology; Bioinformatics; Synthetic genomics; Genome engineering; Microbial evolution; Whole-genome sequencing; Laboratory evolution; Experimental evolution

Citation Formats

Goodman, Daniel B., Kuznetsov, Gleb, Lajoie, Marc J., Ahern, Brian W., Napolitano, Michael G., Chen, Kevin Y., Chen, Changping, and Church, George M. Millstone: software for multiplex microbial genome analysis and engineering. United Kingdom: N. p., 2017. Web. doi:10.1186/s13059-017-1223-1.
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Goodman, Daniel B., Kuznetsov, Gleb, Lajoie, Marc J., Ahern, Brian W., Napolitano, Michael G., Chen, Kevin Y., Chen, Changping, & Church, George M. Millstone: software for multiplex microbial genome analysis and engineering. United Kingdom. https://doi.org/10.1186/s13059-017-1223-1
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Goodman, Daniel B., Kuznetsov, Gleb, Lajoie, Marc J., Ahern, Brian W., Napolitano, Michael G., Chen, Kevin Y., Chen, Changping, and Church, George M. Thu . "Millstone: software for multiplex microbial genome analysis and engineering". United Kingdom. https://doi.org/10.1186/s13059-017-1223-1.
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@article{osti_1618928,
title = {Millstone: software for multiplex microbial genome analysis and engineering},
author = {Goodman, Daniel B. and Kuznetsov, Gleb and Lajoie, Marc J. and Ahern, Brian W. and Napolitano, Michael G. and Chen, Kevin Y. and Chen, Changping and Church, George M.},
abstractNote = {Inexpensive DNA sequencing and advances in genome editing have made computational analysis a major rate-limiting step in adaptive laboratory evolution and microbial genome engineering. Here, we describe Millstone, a web-based platform that automates genotype comparison and visualization for projects with up to hundreds of genomic samples. To enable iterative genome engineering, Millstone allows users to design oligonucleotide libraries and create successive versions of reference genomes. Millstone is open source and easily deployable to a cloud platform, local cluster, or desktop, making it a scalable solution for any lab.},
doi = {10.1186/s13059-017-1223-1},
journal = {Genome Biology (Online)},
number = 1,
volume = 18,
place = {United Kingdom},
year = {Thu May 25 00:00:00 EDT 2017},
month = {Thu May 25 00:00:00 EDT 2017}
}
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Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
https://doi.org/10.1186/s13059-017-1223-1
Copyright Statement
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Citation Metrics:
Cited by: 3 works
Citation information provided by
Web of Science

Figures / Tables:

Fig. 1 Fig. 1: Millstone enables rapid iterative multiplex genome analysis and engineering. a To use Millstone, a researcher uploads a reference genome and next-generation sequencing reads for many individual genomic clones, for example from long-term evolution or targeted genome editing. Millstone performs alignment and variant calling for both single nucleotide variantsmore » and structural variation and then assigns predicted effects based on reference genome annotations. A unified data model stores sample genotype, phenotype, and variant annotation data. Variants can then be queried, filtered, and grouped into sets for export, triage, and analysis. These variant sets can be used to design oligonucleotides to recreate or revert mutations of interest, or used to generate new versions of the reference genome. b A combined screenshot of the Millstone analysis and alignment visualization views (condensed and cropped for clarity). A custom query language and a corresponding query form in the user interface allow searching and filtering over the data. As variant calls sometimes require visual inspection and comparison, Millstone’s variant analysis view provides programmatically generated links to visualizations of the relevant read alignments in JBrowse [18]« less
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