Title: PeakDecoder enables machine learning-based metabolite annotation and accurate profiling in multidimensional mass spectrometry measurements

Abstract

Multidimensional measurements using state-of-the-art separations and mass spectrometry provide advantages in untargeted metabolomics analyses for studying biological and environmental bio-chemical processes. However, the lack of rapid analytical methods and robust algorithms for these heterogeneous data has limited its application. Here, we develop and evaluate a sensitive and high-throughput analytical and computational workflow to enable accurate metabolite profiling. Our workflow combines liquid chromatography, ion mobility spectrometry and data-independent acquisition mass spectrometry with PeakDecoder, a machine learning-based algorithm that learns to distinguish true co-elution and co-mobility from raw data and calculates metabolite identification error rates. We apply PeakDecoder for metabolite profiling of various engineered strains of Aspergillus pseudoterreus, Aspergillus niger, Pseudomonas putida and Rhodosporidium toruloides. Results, validated manually and against selected reaction monitoring and gas-chromatography platforms, show that 2683 features could be confidently annotated and quantified across 116 microbial sample runs using a library built from 64 standards.

Authors:

Bilbao, Aivett  ^[1];

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• Search DOE PAGES for ORCID "0000-0003-2985-8249"

Munoz, Nathalie  ^[1];

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• Search DOE PAGES for ORCID "0000-0002-2723-3512"

Kim, Joonhoon  ^[1];

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• Search DOE PAGES for ORCID "0000-0002-7425-1828"

Orton, Daniel J.  ^[2];

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• Search DOE PAGES for ORCID "0000-0002-0253-6859"

Gao, Yuqian  ^[1];

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• Search DOE PAGES for ORCID "0000-0003-1646-4515"

Poorey, Kunal ^[3]; Pomraning, Kyle R.  ^[1];

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• Search DOE PAGES for ORCID "0000-0003-2324-2881"

Weitz, Karl ^[2]; Burnet, Meagan ^[2]; Nicora, Carrie D.  ^[2];

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Wilton, Rosemarie ^[4]; Deng, Shuang ^[1]; Dai, Ziyu ^[1]; Oksen, Ethan  ^[5];

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• Search DOE PAGES for ORCID "0000-0001-6903-9104"

Gee, Aaron ^[6]; Fasani, Rick A. ^[6]; Tsalenko, Anya ^[6]; Tanjore, Deepti ^[7]; Gardner, James ^[7]; Smith, Richard D.  ^[2]

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more »; Michener, Joshua K.  ^[8];

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• Search DOE PAGES for ORCID "0000-0003-2302-8180"

Gladden, John M. ^[9]; Baker, Erin S.  ^[10];

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Petzold, Christopher J.  ^[7];

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Kim, Young-Mo  ^[1];

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• Search DOE PAGES for ORCID "0000-0002-8972-7593"

Apffel, Alex ^[6]; Magnuson, Jon K.  ^[1];

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• Search DOE PAGES for ORCID "0000-0001-7712-7024"

Burnum-Johnson, Kristin E.  ^[1]

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• Search DOE PAGES for ORCID "0000-0002-2722-4149"

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+ Show Author Affiliations

1. Pacific Northwest National Laboratory (PNNL), Richland, WA (United States); USDOE Agile BioFoundry, Emeryville, CA (United States)
2. Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
3. Sandia National Laboratory (SNL-CA), Livermore, CA (United States)
4. Argonne National Laboratory (ANL), Argonne, IL (United States); USDOE Agile BioFoundry, Emeryville, CA (United States)
5. Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
6. Agilent Technologies, Santa Clara, CA (United States)
7. Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States); USDOE Agile BioFoundry, Emeryville, CA (United States)
8. Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States); USDOE Agile BioFoundry, Emeryville, CA (United States)
9. Sandia National Laboratory (SNL-CA), Livermore, CA (United States); USDOE Agile BioFoundry, Emeryville, CA (United States)
10. University of North Carolina, Chapel Hill, NC (United States)

Publication Date:

Fri Apr 28 00:00:00 EDT 2023

Research Org.:

Argonne National Laboratory (ANL), Argonne, IL (United States); Pacific Northwest National Laboratory (PNNL), Richland, WA (United States); Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)

Sponsoring Org.:

USDOE Office of Energy Efficiency and Renewable Energy (EERE), Office of Sustainable Transportation. Bioenergy Technologies Office (BETO); National Institutes of Health (NIH)

OSTI Identifier:

1994378

Alternate Identifier(s):

OSTI ID: 1973113; OSTI ID: 1996726

Report Number(s):

PNNL-SA-174727
Journal ID: ISSN 2041-1723; 178960

Grant/Contract Number:  

AC02-06CH11357; P41 GM103493; AC05-76RL01830; AC05-00OR22725

Resource Type:

Accepted Manuscript

Journal Name:

Nature Communications

Additional Journal Information:

Journal Volume: 14; Journal Issue: 1; Journal ID: ISSN 2041-1723

Publisher:

Nature Publishing Group

Country of Publication:

United States

Language:

English

Subject:

59 BASIC BIOLOGICAL SCIENCES; HILIC; data-independent acquisition; ion mobility spectrometry; mass spectrometry; metabolomics; synthetic biology; Data processing; Machine learning