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Record W7117303134 · doi:10.1021/acsptsci.5c00658

Direct Injection Mass Spectrometry and iFishMass for the High-Throughput Analysis of Antibody Modifications

2025· article· en· W7117303134 on OpenAlexaff
Jennifer T. Aguilan, Carlos Madrid-Aliste, Fereshteh Zandkarimi, Alexey A. Makarov, Alycia Shoultz, Umme Ayesa, Zachary E. X. Dance, Anumita Saha-Shah, Simone Sidoli

Bibliographic record

VenueACS Pharmacology & Translational Science · 2025
Typearticle
Languageen
FieldChemistry
TopicAdvanced Proteomics Techniques and Applications
Canadian institutionsIONICS Mass Spectrometry (Canada)
FundersEinstein-Mount Sinai Diabetes Research Center, Albert Einstein College of MedicineNIH Office of the DirectorMSD K.K.Hevolution Foundation
KeywordsMass spectrometryPipetteAntibody-drug conjugateMonoclonal antibodyProteomicsSample preparationTandem mass spectrometryDrug discoveryAnalyte

Abstract

fetched live from OpenAlex

High-throughput analysis has become a critical component in chemical biology and analytical chemistry due to the large libraries of compounds that are screened every day for drug development. Mass spectrometry (MS)-based proteomics is the methodology of choice for large-scale identification and quantification of protein modifications, both chemically deposited and biological post-translational modifications (PTMs). With the advent of antibody drug conjugates (ADCs) and other novel protein-based conjugates, the demand for such an analysis has skyrocketed. Here, we present a new protocol that achieves quantitative data for modified peptides in approximately 30 s of MS acquisition time. This platform includes a direct injection MS approach coupled with new software named iFishMass to extract targeted signals from hundreds of runs. iFishMass automatically generates plots and statistics. This platform will enable a faster analysis of synthetic modifications installed on monoclonal antibodies to create ADCs, and it is potentially scalable to biological PTMs. Sample preparation can be parallelized for 384 samples by using multichannel pipettes and 96-well plates, paving the way to an inexpensive but effective platform for high-throughput screening of conjugation sites on proteins.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.737
Threshold uncertainty score0.380

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.002
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.015
GPT teacher head0.361
Teacher spread0.346 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations1
Published2025
Admission routes1
Has abstractyes

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