Evidence map›Paper›PMID 32812765›Full record

ArticleJournal of the American Society for Mass Spectrometry2020

Interlaboratory Study for Characterizing Monoclonal Antibodies by Top-Down and Middle-Down Mass Spectrometry.

Kristina Srzentić, Luca Fornelli, Yury O Tsybin, Joseph A Loo, Henrique Seckler, Jeffrey N Agar, Lissa C Anderson, Dina L Bai, Alain Beck, Jennifer S Brodbelt and 50 more

Registry-linked trialAbstract read
In one paragraph

Article in Journal of the American Society for Mass Spectrometry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05720065 (Peripheral TMD Pain Mechanisms and the Effect by Botulinum Toxin A. A Randomized, Controlled, Double-blind Study), which is not on this map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05720065 phase2recruitingnot on this mapstarted 2023, after this paper: background citation

Peripheral TMD Pain Mechanisms and the Effect by Botulinum Toxin A. A Randomized, Controlled, Double-blind Study

TypeinterventionalSponsorKarolinska InstitutetRan2023 to 2027Enrolled100ConditionsTemporomandibular DisordersArmsBotulinum toxin type A, Isotonic saline 0,9%
3 · Its place in the literature

Who cites it

46 citing papers in PubMed.

  1. Article
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  6. LC-MS/MS method for quantifying the HIV-1 broadly neutralizing antibody PGT 121.414.LS in human serum.Journal of chromatography. B, Analytical technologies in the biomedical and life sciences · 2025
    Article
  7. Article
  8. Article
  9. Top-Down and Middle-Down Mass Spectrometry of Antibodies.Molecular & cellular proteomics : MCP · 2025
    Review
  10. Review
  11. Review
  12. Article
  13. Article
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  15. Article
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  19. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

60 authors.

Kristina SrzentićNorthwestern University, Evanston, Illinois 60208-0001, United States.
Luca FornelliNorthwestern University, Evanston, Illinois 60208-0001, United States.
Yury O TsybinSpectroswiss, EPFL Innovation Park, Building I, 1015 Lausanne, Switzerland.ORCID http://orcid.org/0000-0001-7533-0774
Joseph A LooUniversity of California-Los Angeles, Los Angeles, California 90095, United States.ORCID http://orcid.org/0000-0001-9989-1437
Henrique SecklerNorthwestern University, Evanston, Illinois 60208-0001, United States.
Jeffrey N AgarNortheastern University, Boston, Massachusetts 02115, United States.
Lissa C AndersonNational High Magnetic Field Laboratory, Tallahassee, Florida 32310, United States.ORCID http://orcid.org/0000-0001-8633-0251
Dina L BaiUniversity of Virginia, Charlottesville, Virginia 22901, United States.
Alain BeckCentre d'immunologie Pierre Fabre, 74160 Saint-Julien-en-Genevois, France.ORCID http://orcid.org/0000-0002-4725-1777
Jennifer S BrodbeltUniversity of Texas at Austin, Austin, Texas 78712-1224, United States.ORCID http://orcid.org/0000-0003-3207-0217
Yuri E M van der BurgtLeiden University Medical Centre, 2300 RC Leiden, The Netherlands.ORCID http://orcid.org/0000-0003-0556-5564
Julia Chamot-RookeInstitute Pasteur, 75015 Paris, France.ORCID http://orcid.org/0000-0002-9427-543X
Sneha ChatterjeeUniversity of Antwerp, 2000 Antwerp, Belgium.
Yunqiu ChenBiogen, Inc., Cambridge, Massachusetts 02142-1031, United States.
David J ClarkeThe University of Edinburgh, EH9 3FJ Edinburgh, United Kingdom.ORCID http://orcid.org/0000-0002-3741-2952
Paul O DanisConsortium for Top-Down Proteomics, Cambridge, Massachusetts 02142, United States.
Jolene K DiedrichThe Scripps Research Institute, La Jolla, California 92037, United States.
Robert A D'IppolitoUniversity of Virginia, Charlottesville, Virginia 22901, United States.ORCID http://orcid.org/0000-0001-7542-6629
Mathieu DupréInstitute Pasteur, 75015 Paris, France.ORCID http://orcid.org/0000-0002-1845-0048
Natalia GasilovaEcole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
Ying GeUniversity of Wisconsin-Madison, Madison, Wisconsin 53706, United States.ORCID http://orcid.org/0000-0001-5211-6812
Young Ah GooUniversity of Maryland, Baltimore, Maryland 21201, United States.
David R GoodlettUniversity of Maryland, Baltimore, Maryland 21201, United States.
Sylvester GreerUniversity of Texas at Austin, Austin, Texas 78712-1224, United States.
Kim F HaselmannNovo Nordisk, DK-2760 Malov, Denmark.
Lidong HeNational High Magnetic Field Laboratory, Tallahassee, Florida 32310, United States.
Christopher L HendricksonNational High Magnetic Field Laboratory, Tallahassee, Florida 32310, United States.
Joshua D HinkleUniversity of Virginia, Charlottesville, Virginia 22901, United States.ORCID http://orcid.org/0000-0002-7626-8957
Matthew V HoltBaylor College of Medicine, Houston, Texas 77030-3411, United States.
Sam HughesThe University of Edinburgh, EH9 3FJ Edinburgh, United Kingdom.
Donald F HuntUniversity of Virginia, Charlottesville, Virginia 22901, United States.
Neil L KelleherNorthwestern University, Evanston, Illinois 60208-0001, United States.ORCID http://orcid.org/0000-0002-8815-3372
Anton N KozhinovSpectroswiss, EPFL Innovation Park, Building I, 1015 Lausanne, Switzerland.
Ziqing LinUniversity of Wisconsin-Madison, Madison, Wisconsin 53706, United States.
Christian MalosseInstitute Pasteur, 75015 Paris, France.
Alan G MarshallNational High Magnetic Field Laboratory, Tallahassee, Florida 32310, United States.ORCID http://orcid.org/0000-0001-9375-2532
Laure MeninEcole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
Robert J MillikinUniversity of Wisconsin-Madison, Madison, Wisconsin 53706, United States.ORCID http://orcid.org/0000-0001-7440-3695
Konstantin O NagornovSpectroswiss, EPFL Innovation Park, Building I, 1015 Lausanne, Switzerland.
Simone NicolardiLeiden University Medical Centre, 2300 RC Leiden, The Netherlands.ORCID http://orcid.org/0000-0001-8393-1625
Ljiljana Paša-TolićPacific Northwest National Laboratory, Richland, Washington 99354, United States.
Stuart PengelleyBruker Daltonik GmbH, 28359 Bremen, Germany.ORCID http://orcid.org/0000-0003-2676-8096
Neil R QuebbemannUniversity of California-Los Angeles, Los Angeles, California 90095, United States.
Anja ResemannBruker Daltonik GmbH, 28359 Bremen, Germany.
Wendy SandovalGenentech, Inc., South San Francisco, California 94080-4990, United States.
Richa SarinBiogen, Inc., Cambridge, Massachusetts 02142-1031, United States.
Nicholas D SchmittNortheastern University, Boston, Massachusetts 02115, United States.
Jeffrey ShabanowitzUniversity of Virginia, Charlottesville, Virginia 22901, United States.
Jared B ShawPacific Northwest National Laboratory, Richland, Washington 99354, United States.ORCID http://orcid.org/0000-0002-1130-1728
Michael R ShortreedUniversity of Wisconsin-Madison, Madison, Wisconsin 53706, United States.
Lloyd M SmithUniversity of Wisconsin-Madison, Madison, Wisconsin 53706, United States.
Frank SobottUniversity of Antwerp, 2000 Antwerp, Belgium.ORCID http://orcid.org/0000-0001-9029-1865
Detlev SuckauBruker Daltonik GmbH, 28359 Bremen, Germany.
Timothy TobyNorthwestern University, Evanston, Illinois 60208-0001, United States.
Chad R WeisbrodNational High Magnetic Field Laboratory, Tallahassee, Florida 32310, United States.ORCID http://orcid.org/0000-0001-5324-4525
Norelle C WildburgerWashington University School of Medicine, St. Louis, Missouri 63110, United States.
John R YatesThe Scripps Research Institute, La Jolla, California 92037, United States.ORCID http://orcid.org/0000-0001-5267-1672
Sung Hwan YoonUniversity of Maryland, Baltimore, Maryland 21201, United States.
Nicolas L YoungBaylor College of Medicine, Houston, Texas 77030-3411, United States.ORCID http://orcid.org/0000-0002-3323-2815
Mowei ZhouPacific Northwest National Laboratory, Richland, Washington 99354, United States.ORCID http://orcid.org/0000-0003-3575-3224

Funding

PROTEIN SEQUENCING BY TANDEM MASS SPECTROMETRYR01GM037537 · NIGMS · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI HUNT, DONALD F · 1987 to 2023
$17.8M
Institutional Training in the Genomic SciencesT32HG002760 · NHGRI · UNIVERSITY OF WISCONSIN-MADISON · PI Qiongshi Lu · 2003 to 2026
$17.7M
TR&D 7: Cell Specific ProteomicsP41GM108569 · NIGMS · NORTHWESTERN UNIVERSITY · PI KELLEHER, NEIL L · 2015 to 2024
$13.6M
Revealing Proteoforms: The Primary Effectors of Biological FunctionR35GM126914 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI Lloyd M Smith · 2018 to 2026
$6.2M
UV Laser for Photodissociation-Mass Spectrometry of Proteins and Protein ComplexesR01GM103479 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LOO, JOSEPH A · 2012 to 2021
$3.2M
Chemistry of Life Processes Predoctoral Training ProgramT32GM105538 · NIGMS · NORTHWESTERN UNIVERSITY · PI KELLEHER, NEIL L · 2013 to 2022
$2.7M
Ultra-High Resolution Mass Spectrometer for Biomedical ResearchS10RR028893 · NCRR · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LOO, JOSEPH A · 2010 to 2010
$2.7M
Ultra High Resolution Mass Spectrometer for Biomedical ResearchS10OD018475 · OD · UNIVERSITY OF WISCONSIN-MADISON · PI GE, YING · 2015 to 2015
$2.0M
MASH Explorer, a Comprehensive Software Environment for Top-Down ProteomicsR01GM125085 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI GE, YING · 2018 to 2021
$1.2M
High-Resolution Ion Mobility Mass SpectrometerS10OD018504 · OD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LOO, JOSEPH A · 2014 to 2014
$915k
NCRR NIH HHS S10 RR028893NHGRI NIH HHS T32 HG002760NIGMS NIH HHS P41 GM108569NIGMS NIH HHS R01 GM037537NIGMS NIH HHS R01 GM103479NIGMS NIH HHS R01 GM125085NIGMS NIH HHS R35 GM126914NIGMS NIH HHS T32 GM105538NIH HHS S10 OD018475NIH HHS S10 OD018504
6 · The paper itself

Abstract

The Consortium for Top-Down Proteomics (www.topdownproteomics.org) launched the present study to assess the current state of top-down mass spectrometry (TD MS) and middle-down mass spectrometry (MD MS) for characterizing monoclonal antibody (mAb) primary structures, including their modifications. To meet the needs of the rapidly growing therapeutic antibody market, it is important to develop analytical strategies to characterize the heterogeneity of a therapeutic product's primary structure accurately and reproducibly. The major objective of the present study is to determine whether current TD/MD MS technologies and protocols can add value to the more commonly employed bottom-up (BU) approaches with regard to confirming protein integrity, sequencing variable domains, avoiding artifacts, and revealing modifications and their locations. We also aim to gather information on the common TD/MD MS methods and practices in the field. A panel of three mAbs was selected and centrally provided to 20 laboratories worldwide for the analysis: Sigma mAb standard (SiLuLite), NIST mAb standard, and the therapeutic mAb Herceptin (trastuzumab). Various MS instrument platforms and ion dissociation techniques were employed. The present study confirms that TD/MD MS tools are available in laboratories worldwide and provide complementary information to the BU approach that can be crucial for comprehensive mAb characterization. The current limitations, as well as possible solutions to overcome them, are also outlined. A primary limitation revealed by the results of the present study is that the expert knowledge in both experiment and data analysis is indispensable to practice TD/MD MS.

Indexed as

Antibodies, MonoclonalAnimalsComplementarity Determining RegionsHumansMass SpectrometryMiceProteomicsAntibodies, MonoclonalComplementarity Determining RegionsFourier transform mass spectrometryFTMSglycoformintact mass measurementMS/MStandem mass spectrometryTherapeutic protein

Identifiers

PMID32812765
PMCPMC7539639

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.