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Lee Cantrell

@leecantrell.bsky.social

320 followers 369 following 99 posts

Biological Mass Spectrometry Proteomics at Scale Scientist at Seer Opinions independent of employer

Lee Cantrell @leecantrell.bsky.social · 30/07/2026

We found that peak area as proxy for peak height and peak symmetry have strong impact on quantification accuracy, independent of datapoints per peak. Peak measurement precision is more reliant on datapoints per peak. Simulations were used to support this observation. 4/6

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Lee Cantrell @leecantrell.bsky.social · 30/07/2026

We also applied synthetic sampling to a biological cohort. Under reasonable study design at appreciable depth with Proteograph XT processed plasma, statistical power is achieved at native measurement. However, accelerated throughput degraded statistically powered and significant IDs. 3/6

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Lee Cantrell @leecantrell.bsky.social · 30/07/2026

While IDs and may be reasonably stable, quantification quality is notably impaired. Using a matrix-matched calibration curve framework, ratios over multiple orders of magnitude are assessed for linear response on a bi-linear fit model. 2/6

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Lee Cantrell @leecantrell.bsky.social · 18/05/2026

8/ IDs are not the output to biology. Well-quantified ions are. Power can occur with reasonably balanced, appropriately sized cohorts at realistic precision, but ID expansion should rely on high-quality acquisition. Benchmark MS methods by LOQ yield, peak shape, and sample context, not IDs alone.

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Lee Cantrell @leecantrell.bsky.social · 18/05/2026

7/ In a 20 vs 20 plasma case-control cohort, reduced sampling preserved broad fold-change structure but eroded q-value concordance, achieved power, and BH-significant + powered precursors. Losses were enriched among lower-abundance features.

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Lee Cantrell @leecantrell.bsky.social · 18/05/2026

6/ Simulations recapitulated the pattern. Increasing DPPP mainly reduced integration variance. But integration accuracy remained governed by SNR, baseline/noise structure, and peak asymmetry. More scans help; they do not rescue poor chromatography or weak signal.

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Lee Cantrell @leecantrell.bsky.social · 18/05/2026

5/ DPPP was useful but incomplete. Low DPPP did not mean peaks were non-quantitative. Integration accuracy and precision were more governed by peak area than by DPPP alone. Peak context mattered more than a single sampling proxy.

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Lee Cantrell @leecantrell.bsky.social · 18/05/2026

4/ Key observation: LOD was comparatively resilient to reduced DPPP, while LOQ degraded strongly. Precursors could remain detectable yet lose the linearity and precision needed for quantitative interpretation.

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Lee Cantrell @leecantrell.bsky.social · 18/05/2026

www.biorxiv.org/content/10.6... 1/ Proteomics method development often optimizes for IDs. But for cohort biology, IDs only matter if they remain quantitative, precise, and powered. We ask how chromatographic sampling density propagates from peaks → LOQ → discovery. 🧵

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