Evidence map›Paper›PMID 36457147›Full record

ArticleRNA biology2022

Characterization of protein isoform diversity in human umbilical vein endothelial cells via long-read proteogenomics.

Madison M Mehlferber, Erin D Jeffery, Jamie Saquing, Ben T Jordan, Leon Sheynkman, Mayank Murali, Gael Genet, Bipul R Acharya, Karen K Hirschi, Gloria M Sheynkman

Open access · goldAbstract read
In one paragraph

Article in RNA biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.3field-weighted citation impact, top 20% 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

11 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. Review
  3. Perplexity as a Metric for Isoform Diversity in the Human Transcriptome.bioRxiv : the preprint server for biology · 2025
    Article
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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

10 authors at 2 institutions in 2 countries.

Madison M MehlferberDepartment of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA, USA.
Erin D JefferyDepartment of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia, USA.
Jamie SaquingDepartment of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia, USA.
Ben T JordanDepartment of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia, USA.
Leon SheynkmanDepartment of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia, USA.
Mayank MuraliDepartment of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia, USA.
Gael GenetDepartment of Cell Biology, University of Virginia School of Medicine, Charlottesville, VA, USA.
Bipul R AcharyaDepartment of Cell Biology, University of Virginia School of Medicine, Charlottesville, VA, USA.
Karen K HirschiDepartment of Cell Biology, University of Virginia School of Medicine, Charlottesville, VA, USA.
Gloria M SheynkmanDepartment of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA, USA.ORCID 0000-0002-4223-9947
University of Virginia · USWellcome Centre for Cell-Matrix Research · GB

Funding

BASIC CARDIOVASCULAR RESEARCH TRAINING GRANTT32HL007284 · NHLBI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI Brant E Isakson, Gary K Owens · 1985 to 2026
$19.6M
Defining SMC phenotypes critical in late stage atherosclerosis pathogenesisR01HL136314 · NHLBI · UNIVERSITY OF VIRGINIA · PI OWENS, GARY K · 2018 to 2021
$3.0M
miR-223 regulates endothelial to hematopoietic transitionR01DK118728 · NIDDK · YALE UNIVERSITY · PI HIRSCHI, KAREN KEMPER, NICOLI, STEFANIA · 2020 to 2023
$2.9M
Endothelial Cell Cycle State and Cell FateR01HL146056 · NHLBI · UNIVERSITY OF VIRGINIA · PI HIRSCHI, KAREN KEMPER · 2019 to 2022
$2.1M
Uncovering the functional diversification mechanisms of transcription factor isoforms involved in stem cell differentiationR35GM142647 · NIGMS · UNIVERSITY OF VIRGINIA · PI SHEYNKMAN, GLORIA · 2021 to 2025
$2.1M
miR-223 regulates endothelial to hematopoietic transitionR56DK118728 · NIDDK · YALE UNIVERSITY · PI HIRSCHI, KAREN KEMPER, NICOLI, STEFANIA · 2018 to 2018
$100k
NHLBI NIH HHS R01 HL136314NHLBI NIH HHS R01 HL146056NHLBI NIH HHS T32 HL007284NIDDK NIH HHS R01 DK118728NIDDK NIH HHS R56 DK118728NIGMS NIH HHS R35 GM142647
6 · The paper itself

Abstract

Endothelial cells (ECs) comprise the lumenal lining of all blood vessels and are critical for the functioning of the cardiovascular system. Their phenotypes can be modulated by alternative splicing of RNA to produce distinct protein isoforms. To characterize the RNA and protein isoform landscape within ECs, we applied a long read proteogenomics approach to analyse human umbilical vein endothelial cells (HUVECs). Transcripts delineated from PacBio sequencing serve as the basis for a sample-specific protein database used for downstream mass-spectrometry (MS) analysis to infer protein isoform expression. We detected 53,863 transcript isoforms from 10,426 genes, with 22,195 of those transcripts being novel. Furthermore, the predominant isoform in HUVECs does not correspond with the accepted "reference isoform" 25% of the time, with vascular pathway-related genes among this group. We found 2,597 protein isoforms supported through unique peptides, with an additional 2,280 isoforms nominated upon incorporation of long-read transcript evidence. We characterized a novel alternative acceptor for endothelial-related gene CDH5, suggesting potential changes in its associated signalling pathways. Finally, we identified novel protein isoforms arising from a diversity of RNA splicing mechanisms supported by uniquely mapped novel peptides. Our results represent a high-resolution atlas of known and novel isoforms of potential relevance to endothelial phenotypes and function.[Figure: see text].

Indexed as

ProteogenomicsAlternative SplicingHumansHuman Umbilical Vein Endothelial CellsProtein IsoformsRNAProtein IsoformsRNAalternative splicingcardiovascularendothelial cellsHUVECsisoformsLong-read RNA-seqmass-spectrometry-based proteomicsMetaMorpheusnextflowOrbitrapPacBioprotein isoformsproteogenomics

Identifiers

PMID36457147
PMCPMC9721438
OpenAlexW4307811641

What Socratic 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 Socratic graph.