Peak-tracking algorithm for use in comprehensive two-dimensional liquid chromatography – Application to monoclonal-antibody peptides

Stef R.A. Molenaar; Tina A. Dahlseid; Gabriel M. Leme; Dwight R. Stoll; Peter J. Schoenmakers; Bob W.J. Pirok

doi:10.1016/j.chroma.2021.461922

Peak-tracking algorithm for use in comprehensive two-dimensional liquid chromatography – Application to monoclonal-antibody peptides

Stef R.A. Molenaar, Tina A. Dahlseid, Gabriel M. Leme, Dwight R. Stoll, Peter J. Schoenmakers, Bob W.J. Pirok

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

Abstract

A peak-tracking algorithm was developed for use in comprehensive two-dimensional liquid chromatography coupled to mass spectrometry. Chromatographic peaks were tracked across two different chromatograms, utilizing the available spectral information, the statistical moments of the peaks and the relative retention times in both dimensions. The algorithm consists of three branches. In the pre-processing branch, system peaks are removed based on mass spectra compared to low intensity regions and search windows are applied, relative to the retention times in each dimension, to reduce the required computational power by elimination unlikely pairs. In the comparison branch, similarity between the spectral information and statistical moments of peaks within the search windows is calculated. Lastly, in the evaluation branch extracted-ion-current chromatograms are utilized to assess the validity of the pairing results. The algorithm was applied to peptide retention data recorded under varying chromatographic conditions for use in retention modelling as part of method optimization tools. Moreover, the algorithm was applied to complex peptide mixtures obtained from enzymatic digestion of monoclonal antibodies. The algorithm yielded no false positives. However, due to limitations in the peak-detection algorithm, cross-pairing within the same peaks occurred and six trace compounds remained falsely unpaired.

Original language	English
Article number	461922
Journal	Journal of Chromatography A
Volume	1639
DOIs	https://doi.org/10.1016/j.chroma.2021.461922
Publication status	Published - 22 Feb 2021
Externally published	Yes

Funding

SM acknowledges the UNMATCHED project, which is supported by BASF, DSM and Nouryon, and receives funding from the Dutch Research Council ( NWO ) in the framework of the Innovation Fund for Chemistry and from the Ministry of Economic Affairs in the framework of the “PPS-toeslagregeling”. TD, GL, and DS acknowledge support from an Agilent Thought Leader Award from Agilent Technologies. The instrumentation and columns used for this work were provided by Agilent. BP acknowledges the Agilent UR grant # 4354 . Dr. Andrea F.G. Gargano is acknowledged for his useful revisions of the manuscript. The authors would like to thank Dr. Gregory Staples for the provided peptide samples. SM acknowledges the UNMATCHED project, which is supported by BASF, DSM and Nouryon, and receives funding from the Dutch Research Council (NWO) in the framework of the Innovation Fund for Chemistry and from the Ministry of Economic Affairs in the framework of the ?PPS-toeslagregeling?. TD, GL, and DS acknowledge support from an Agilent Thought Leader Award from Agilent Technologies. The instrumentation and columns used for this work were provided by Agilent. BP acknowledges the Agilent UR grant #4354. Dr. Andrea F.G. Gargano is acknowledged for his useful revisions of the manuscript. The authors would like to thank Dr. Gregory Staples for the provided peptide samples. This work was performed in the context of the Chemometrics and Advanced Separations Team (CAST) within the Centre for Analytical Sciences Amsterdam (CASA). The valuable contributions of the CAST members are gratefully acknowledged.

Funders	Funder number
Agilent UR	4354
Agilent Technologies
BASF
Diagnostic Services Manitoba
Ministerie van Economische Zaken
Nederlandse Organisatie voor Wetenschappelijk Onderzoek
China Academy of Space Technology
DSM Research

UN SDGs

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title = "Peak-tracking algorithm for use in comprehensive two-dimensional liquid chromatography – Application to monoclonal-antibody peptides",

abstract = "A peak-tracking algorithm was developed for use in comprehensive two-dimensional liquid chromatography coupled to mass spectrometry. Chromatographic peaks were tracked across two different chromatograms, utilizing the available spectral information, the statistical moments of the peaks and the relative retention times in both dimensions. The algorithm consists of three branches. In the pre-processing branch, system peaks are removed based on mass spectra compared to low intensity regions and search windows are applied, relative to the retention times in each dimension, to reduce the required computational power by elimination unlikely pairs. In the comparison branch, similarity between the spectral information and statistical moments of peaks within the search windows is calculated. Lastly, in the evaluation branch extracted-ion-current chromatograms are utilized to assess the validity of the pairing results. The algorithm was applied to peptide retention data recorded under varying chromatographic conditions for use in retention modelling as part of method optimization tools. Moreover, the algorithm was applied to complex peptide mixtures obtained from enzymatic digestion of monoclonal antibodies. The algorithm yielded no false positives. However, due to limitations in the peak-detection algorithm, cross-pairing within the same peaks occurred and six trace compounds remained falsely unpaired.",

author = "Molenaar, {Stef R.A.} and Dahlseid, {Tina A.} and Leme, {Gabriel M.} and Stoll, {Dwight R.} and Schoenmakers, {Peter J.} and Pirok, {Bob W.J.}",

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AU - Leme, Gabriel M.

AU - Stoll, Dwight R.

AU - Schoenmakers, Peter J.

AU - Pirok, Bob W.J.

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Peak-tracking algorithm for use in comprehensive two-dimensional liquid chromatography – Application to monoclonal-antibody peptides

Abstract

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UN SDGs

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