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Sensitive and Comprehensive Lipid Mediator Analysis using Advanced Scheduled MRM with Polarity Switching and QTRAP Enhanced Product Ion Scanning

2020· article· en· W3017736921 on OpenAlexaff
Paul C. Norris, Mackenzie Pearson, Santosh Kapil, Baljit K. Ubhi

Bibliographic record

VenueThe FASEB Journal · 2020
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMetabolomics and Mass Spectrometry Studies
Canadian institutionsSciex (Canada)
Fundersnot available
KeywordsChemistryLipid signalingLipidomicsMediatorAnalyteChromatographyLipid metabolismBiochemistryEnzymeCell biologyBiology

Abstract

fetched live from OpenAlex

Using a QTRAP® 6500+ system coupled with an ExionLC™ System, we developed a targeted panel of 88 compounds for comprehensive profiling of lipid mediators and pathway markers. A Kinetex® Polar C18 column was used for LC based separation of lipid mediators, epimers and other isoelemental structures within a 20 min run time. Advanced scheduled sMRM was used to optimize scanning windows and dwell weighting. The negative mode lipid mediator panel includes pro‐inflammatory prostaglandins, leukotrienes and their primary metabolites, specialized pro‐resolving mediators (SPM) including resolvins, protectins, maresins, and lipoxins, biomarkers of ROS and NOS, and fatty acid and mono‐hydroxy fatty acid precursors. The positive mode panel includes cysteinyl leukotrienes, PAF, and maresin and protectin conjugates in tissue regeneration (MCTRs and PCTRs). Concentration curves were generated by injecting 3 replicate injections of 8 different concentrations of each lipid mediator standard. Excellent linearity is observed with r 2 of at least 0.997 for all analytes. Excellent sensitivity was obtained for all lipid mediator species with LLOQ between 0.05 and 1 ng/mL and CV < 30%. The unique qualitative/quantitative QTRAP platform also enabled MRM triggered EPI experiments which provided high sensitivity MS/MS data for confirmation of low level analytes. Baseline separation of LXA 4 and 15‐epi‐LXA 4 well as RvD1 and 17‐epi‐RvD1 enables the differentiation of enzymatic pathway utilization for pro‐resolving lipid mediator production.

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)0.003
metaresearch head score (Gemma)0.002
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: Empirical · Consensus signal: none
Teacher disagreement score0.004
Threshold uncertainty score0.015

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0030.002
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0020.001
Science and technology studies0.0010.001
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0040.002

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 head0.250
Teacher spread0.236 · 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
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
Published2020
Admission routes1
Has abstractyes

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