Evidence map›Paper›PMID 34861815›Full record

ArticleClinical proteomics2021

A validated analysis pipeline for mass spectrometry-based vitreous proteomics: new insights into proliferative diabetic retinopathy.

Sarah R Weber, Yuanjun Zhao, Jingqun Ma, Christopher Gates, Felipe da Veiga Leprevost, Venkatesha Basrur, Alexey I Nesvizhskii, Thomas W Gardner, Jeffrey M Sundstrom

Open access · goldAbstract read
In one paragraph

Article in Clinical proteomics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.3field-weighted citation impact, top 21% of its field
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 10 citations in OpenAlex.

  1. Artificial intelligence in diabetic retinopathy: from automated screening to risk-stratified care.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026
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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

9 authors at 5 institutions in 1 country.

Sarah R WeberDepartment of Ophthalmology, Penn State College of Medicine, 500 University Drive, Hershey, PA, 17033, USA.
Yuanjun ZhaoDepartment of Ophthalmology, Penn State College of Medicine, 500 University Drive, Hershey, PA, 17033, USA.
Jingqun MaDepartment of Pathology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38105, USA.
Christopher GatesBioinformatics Core, Biomedical Research Core Facilities, University of Michigan Medical School, 2800 Plymouth Road, Ann Arbor, MI, 48109, USA.
Felipe da Veiga LeprevostDepartment of Pathology, University of Michigan Medical School, 1301 Catherine Street, Ann Arbor, MI, 48109, USA.
Venkatesha BasrurDepartment of Pathology, University of Michigan Medical School, 1301 Catherine Street, Ann Arbor, MI, 48109, USA.
Alexey I NesvizhskiiDepartment of Pathology, University of Michigan Medical School, 1301 Catherine Street, Ann Arbor, MI, 48109, USA.
Thomas W GardnerKellogg Eye Center, University of Michigan Medical School, 1000 Wall Street, Ann Arbor, MI, 48105, USA.
Jeffrey M SundstromDepartment of Ophthalmology, Penn State College of Medicine, 500 University Drive, Hershey, PA, 17033, USA. jsundstrom@pennstatehealth.psu.edu.ORCID http://orcid.org/0000-0003-2738-2224
University of Michigan · USW.K. Kellogg Foundation · USPennsylvania State University · USSt. Jude Children's Research Hospital · USWashtenaw Community College · US

Funding

XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Alexey I Nesvizhskii · 1988 to 2026
$178.2M
Regional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Mehboob A Hussain · 2013 to 2026
$24.3M
COMPUTATIONAL TOOLS FOR MASS SPECTROMETRY-BASED INTERACTOME DATAR01GM094231 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Alexey I Nesvizhskii · 2010 to 2026
$5.4M
NCI NIH HHS P30 CA046592NIDDK NIH HHS P30 DK020572NIGMS NIH HHS R01 GM094231
6 · The paper itself

Abstract

backgroundVitreous is an accessible, information-rich biofluid that has recently been studied as a source of retinal disease-related proteins and pathways. However, the number of samples required to confidently identify perturbed pathways remains unknown. In order to confidently identify these pathways, power analysis must be performed to determine the number of samples required, and sample preparation and analysis must be rigorously defined.

methodsControl (n = 27) and proliferative diabetic retinopathy (n = 23) vitreous samples were treated as biologically distinct individuals or pooled together and aliquoted into technical replicates. Quantitative mass spectrometry with tandem mass tag labeling was used to identify proteins in individual or pooled control samples to determine technical and biological variability. To determine effect size and perform power analysis, control and proliferative diabetic retinopathy samples were analyzed across four 10-plexes. Pooled samples were used to normalize the data across plexes and generate a single data matrix for downstream analysis.

resultsThe total number of unique proteins identified was 1152 in experiment 1, 989 of which were measured in all samples. In experiment 2, 1191 proteins were identified, 727 of which were measured across all samples in all plexes. Data are available via ProteomeXchange with identifier PXD025986. Spearman correlations of protein abundance estimations revealed minimal technical (0.99-1.00) and biological (0.94-0.98) variability. Each plex contained two unique pooled samples: one for normalizing across each 10-plex, and one to internally validate the normalization algorithm. Spearman correlation of the validation pool following normalization was 0.86-0.90. Principal component analysis revealed stratification of samples by disease and not by plex. Subsequent differential expression and pathway analyses demonstrated significant activation of metabolic pathways and inhibition of neuroprotective pathways in proliferative diabetic retinopathy samples relative to controls.

conclusionsThis study demonstrates a feasible, rigorous, and scalable method that can be applied to future proteomic studies of vitreous and identifies previously unrecognized metabolic pathways that advance understanding of diabetic retinopathy.

Indexed as

Diabetic retinopathyMass spectrometryPower analysisPrecision medicineProteomicsRetinal diseaseVitreous

Identifiers

PMID34861815
PMCPMC8903510
OpenAlexW3185621400

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.