The One Hour Human Proteome

Lia R. Serrano; Trenton M. Peters-Clarke; Tabiwang N. Arrey; Eugen Damoc; Margaret Lea Robinson; Noah M. Lancaster; Evgenia Shishkova; Corinne Moss; Anna Pashkova; Pavel Sinitcyn; Dain R. Brademan; Scott T. Quarmby; Amelia C. Peterson; Martin Zeller; Daniel Hermanson; Hamish Stewart; Christian Hock; Alexander Makarov; Vlad Zabrouskov; Joshua J. Coon

doi:10.1016/j.mcpro.2024.100760

The One Hour Human Proteome

Lia R. Serrano, Trenton M. Peters-Clarke, Tabiwang N. Arrey, Eugen Damoc, Margaret Lea Robinson, Noah M. Lancaster, Evgenia Shishkova, Corinne Moss, Anna Pashkova, Pavel Sinitcyn, Dain R. Brademan, Scott T. Quarmby, Amelia C. Peterson, Martin Zeller, Daniel Hermanson, Hamish Stewart, Christian Hock, Alexander Makarov, Vlad Zabrouskov, Joshua J. Coon^*

^*Corresponding author for this work

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Research output: Contribution to journal › Article › Academic › peer-review

Abstract

We describe deep analysis of the human proteome in less than 1 h. We achieve this expedited proteome characterization by leveraging state-of-the-art sample preparation, chromatographic separations, and data analysis tools, and by using the new Orbitrap Astral mass spectrometer equipped with a quadrupole mass filter, a high-field Orbitrap mass analyzer, and an asymmetric track lossless (Astral) mass analyzer. The system offers high tandem mass spectrometry acquisition speed of 200 Hz and detects hundreds of peptide sequences per second within data-independent acquisition or data-dependent acquisition modes of operation. The fast-switching capabilities of the new quadrupole complement the sensitivity and fast ion scanning of the Astral analyzer to enable narrow-bin data-independent analysis methods. Over a 30-min active chromatographic method consuming a total analysis time of 56 min, the Q-Orbitrap-Astral hybrid MS collects an average of 4319 MS1 scans and 438,062 tandem mass spectrometry scans per run, producing 235,916 peptide sequences (1% false discovery rate). On average, each 30-min analysis achieved detection of 10,411 protein groups (1% false discovery rate). We conclude, with these results and alongside other recent reports, that the 1-h human proteome is within reach.

Original language	English
Article number	100760
Journal	Molecular & Cellular Proteomics
Volume	23
Issue number	5
DOIs	https://doi.org/10.1016/j.mcpro.2024.100760
Publication status	Published - May 2024

Bibliographical note

Publisher Copyright:
© 2024 THE AUTHORS. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology.

Funding

The authors thank other members of the Coon Lab and the many employees of Thermo Fisher Scientific without whom this work would not be possible. This work was supported in part by a sponsored research agreement with Thermo Fisher Scientific (J. J. C.), the National Institute of General Medical Sciences of the National Institutes of Health (grants P41GM108538 and R35GM118110 to J. J. C.), and the National Human genome Research Institution through a training grant to the Genomic Science Training Program (grant T32HG002760 to L. R. S.). T. M. P.-C. acknowledges the ACS Division of Analytical Chemistry and Agilent for support through a graduate fellowship. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. ported in part by a sponsored research agreement with Thermo Fisher Scientific (J. J. C.), the National Institute of General Medical Sciences of the National Institutes of Health (grants P41GM108538 and R35GM118110 to J. J. C.), and the National Human genome Research Institution through a training grant to the Genomic Science Training Program (grant T32HG002760 to L. R. S.). T. M. P.-C. acknowledges the ACS Division of Analytical Chemistry and Agilent for support through a graduate fellowship. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Funders	Funder number
National Institute of General Medical Sciences
National Institutes of Health	R35GM118110, P41GM108538
National Institutes of Health
National Human Genome Research Institute	T32HG002760
National Human Genome Research Institute

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Serrano, L. R., Peters-Clarke, T. M., Arrey, T. N., Damoc, E., Robinson, M. L., Lancaster, N. M., Shishkova, E., Moss, C., Pashkova, A., Sinitcyn, P., Brademan, D. R., Quarmby, S. T., Peterson, A. C., Zeller, M., Hermanson, D., Stewart, H., Hock, C., Makarov, A., Zabrouskov, V., & Coon, J. J. (2024). The One Hour Human Proteome. Molecular & Cellular Proteomics, 23(5), Article 100760. https://doi.org/10.1016/j.mcpro.2024.100760

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title = "The One Hour Human Proteome",

abstract = "We describe deep analysis of the human proteome in less than 1 h. We achieve this expedited proteome characterization by leveraging state-of-the-art sample preparation, chromatographic separations, and data analysis tools, and by using the new Orbitrap Astral mass spectrometer equipped with a quadrupole mass filter, a high-field Orbitrap mass analyzer, and an asymmetric track lossless (Astral) mass analyzer. The system offers high tandem mass spectrometry acquisition speed of 200 Hz and detects hundreds of peptide sequences per second within data-independent acquisition or data-dependent acquisition modes of operation. The fast-switching capabilities of the new quadrupole complement the sensitivity and fast ion scanning of the Astral analyzer to enable narrow-bin data-independent analysis methods. Over a 30-min active chromatographic method consuming a total analysis time of 56 min, the Q-Orbitrap-Astral hybrid MS collects an average of 4319 MS1 scans and 438,062 tandem mass spectrometry scans per run, producing 235,916 peptide sequences (1% false discovery rate). On average, each 30-min analysis achieved detection of 10,411 protein groups (1% false discovery rate). We conclude, with these results and alongside other recent reports, that the 1-h human proteome is within reach.",

author = "Serrano, {Lia R.} and Peters-Clarke, {Trenton M.} and Arrey, {Tabiwang N.} and Eugen Damoc and Robinson, {Margaret Lea} and Lancaster, {Noah M.} and Evgenia Shishkova and Corinne Moss and Anna Pashkova and Pavel Sinitcyn and Brademan, {Dain R.} and Quarmby, {Scott T.} and Peterson, {Amelia C.} and Martin Zeller and Daniel Hermanson and Hamish Stewart and Christian Hock and Alexander Makarov and Vlad Zabrouskov and Coon, {Joshua J.}",

note = "Publisher Copyright: {\textcopyright} 2024 THE AUTHORS. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology.",

year = "2024",

month = may,

doi = "10.1016/j.mcpro.2024.100760",

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Serrano, LR, Peters-Clarke, TM, Arrey, TN, Damoc, E, Robinson, ML, Lancaster, NM, Shishkova, E, Moss, C, Pashkova, A, Sinitcyn, P, Brademan, DR, Quarmby, ST, Peterson, AC, Zeller, M, Hermanson, D, Stewart, H, Hock, C, Makarov, A, Zabrouskov, V & Coon, JJ 2024, 'The One Hour Human Proteome', Molecular & Cellular Proteomics, vol. 23, no. 5, 100760. https://doi.org/10.1016/j.mcpro.2024.100760

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T1 - The One Hour Human Proteome

AU - Serrano, Lia R.

AU - Peters-Clarke, Trenton M.

AU - Arrey, Tabiwang N.

AU - Damoc, Eugen

AU - Robinson, Margaret Lea

AU - Lancaster, Noah M.

AU - Shishkova, Evgenia

AU - Moss, Corinne

AU - Pashkova, Anna

AU - Sinitcyn, Pavel

AU - Brademan, Dain R.

AU - Quarmby, Scott T.

AU - Peterson, Amelia C.

AU - Zeller, Martin

AU - Hermanson, Daniel

AU - Stewart, Hamish

AU - Hock, Christian

AU - Makarov, Alexander

AU - Zabrouskov, Vlad

AU - Coon, Joshua J.

PY - 2024/5

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N2 - We describe deep analysis of the human proteome in less than 1 h. We achieve this expedited proteome characterization by leveraging state-of-the-art sample preparation, chromatographic separations, and data analysis tools, and by using the new Orbitrap Astral mass spectrometer equipped with a quadrupole mass filter, a high-field Orbitrap mass analyzer, and an asymmetric track lossless (Astral) mass analyzer. The system offers high tandem mass spectrometry acquisition speed of 200 Hz and detects hundreds of peptide sequences per second within data-independent acquisition or data-dependent acquisition modes of operation. The fast-switching capabilities of the new quadrupole complement the sensitivity and fast ion scanning of the Astral analyzer to enable narrow-bin data-independent analysis methods. Over a 30-min active chromatographic method consuming a total analysis time of 56 min, the Q-Orbitrap-Astral hybrid MS collects an average of 4319 MS1 scans and 438,062 tandem mass spectrometry scans per run, producing 235,916 peptide sequences (1% false discovery rate). On average, each 30-min analysis achieved detection of 10,411 protein groups (1% false discovery rate). We conclude, with these results and alongside other recent reports, that the 1-h human proteome is within reach.

AB - We describe deep analysis of the human proteome in less than 1 h. We achieve this expedited proteome characterization by leveraging state-of-the-art sample preparation, chromatographic separations, and data analysis tools, and by using the new Orbitrap Astral mass spectrometer equipped with a quadrupole mass filter, a high-field Orbitrap mass analyzer, and an asymmetric track lossless (Astral) mass analyzer. The system offers high tandem mass spectrometry acquisition speed of 200 Hz and detects hundreds of peptide sequences per second within data-independent acquisition or data-dependent acquisition modes of operation. The fast-switching capabilities of the new quadrupole complement the sensitivity and fast ion scanning of the Astral analyzer to enable narrow-bin data-independent analysis methods. Over a 30-min active chromatographic method consuming a total analysis time of 56 min, the Q-Orbitrap-Astral hybrid MS collects an average of 4319 MS1 scans and 438,062 tandem mass spectrometry scans per run, producing 235,916 peptide sequences (1% false discovery rate). On average, each 30-min analysis achieved detection of 10,411 protein groups (1% false discovery rate). We conclude, with these results and alongside other recent reports, that the 1-h human proteome is within reach.

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DO - 10.1016/j.mcpro.2024.100760

M3 - Article

SN - 1535-9476

VL - 23

JO - Molecular & Cellular Proteomics

JF - Molecular & Cellular Proteomics

IS - 5

M1 - 100760

ER -

The One Hour Human Proteome

Abstract

Bibliographical note

Funding

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