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Record W4403601158 · doi:10.1002/ange.202409446

A Proteomics Pipeline for Generating Clinical Grade Biomarker Candidates from Data‐Independent Acquisition Mass Spectrometry (DIA‐MS) Discovery

2024· article· en· W4403601158 on OpenAlexaff
Qin Fu, Manasa Vegesna, Niveda Sundararaman, Eugen Damoc, Tabiwang N. Arrey, Anna Pashkova, Emebet Mengesha, Philip Debbas, Sandy Joung, Dalin Li, Susan Cheng, Jonathan Braun, Dermot Govern, Christopher I. Murray, Yue Xuan, Jennifer E. Van Eyk

Bibliographic record

VenueAngewandte Chemie · 2024
Typearticle
Languageen
FieldChemistry
TopicAdvanced Proteomics Techniques and Applications
Canadian institutionsThermo Fisher Scientific (Canada)
FundersNational Institute of Diabetes and Digestive and Kidney DiseasesNational Institutes of HealthLeona M. and Harry B. Helmsley Charitable Trust
KeywordsMass spectrometryProteomicsBiomarker discoveryPipeline (software)ChemistryBiomarkerChromatographyComputer scienceBiochemistry

Abstract

fetched live from OpenAlex

Abstract Clinical biomarker development has been stymied by inaccurate protein quantification from mass spectrometry (MS) discovery data and a prolonged validation process. To mitigate these issues, we created the Targeted Extraction Assessment of Quantification (TEAQ) software package that uses data‐independent acquisition analysis from a discovery cohort to select precursors, peptides, and proteins that adhere to analytical criteria required for established targeted assays. TEAQ was applied to DIA‐MS data from plasma samples acquired on a new high resolution accurate mass (HRAM) mass spectrometry platform where precursors were evaluated for linearity, specificity, repeatability, reproducibility, and intra‐protein correlation based on 8‐ or 11‐point loading curves at three throughputs. This data can be used as a general resource for developing other targeted assays. TEAQ analysis of data from a case and control cohort for inflammatory bowel disease (n=492) identified 1110 signature peptides for 326 quantifiable proteins from the 1179 identified proteins. Applying TEAQ analysis to discovery data will streamline targeted assay development and the transition to validation and clinical studies.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.007
metaresearch head score (Gemma)0.006
Version: metacan-v3-hybrid-931329e0061cValidation 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: Methods · Consensus signal: Methods
Teacher disagreement score0.007
Threshold uncertainty score0.038

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0070.006
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0030.002
Science and technology studies0.0010.000
Scholarly communication0.0030.002
Open science0.0010.002
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0030.005

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 head0.048
GPT teacher head0.347
Teacher spread0.299 · 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 source (direct Gemma or distilled Codex), not a consensus.

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

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

Citations3
Published2024
Admission routes1
Has abstractyes

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