Evidence map›Paper›PMID 29599435›Full record

ArticleScientific reports2018

Improved efficiency of in situ protein analysis by proximity ligation using UnFold probes.

Axel Klaesson, Karin Grannas, Tonge Ebai, Johan Heldin, Björn Koos, Mattias Leino, Doroteya Raykova, Johan Oelrich, Linda Arngården, Ola Söderberg and 1 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

37 citing papers in PubMed, 53 citations in OpenAlex.

  1. Article
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  3. A Spatiotemporal Atlas of the Androgen Receptor Proximal Interactome.bioRxiv : the preprint server for biology · 2026
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  4. Seeing Invisible Oligomers: Rethinking α-Synuclein Pathology Through Proximity Ligation Assay.Movement disorders : official journal of the Movement Disorder Society · 2026
    Review
  5. Article
  6. Single-Cell Protein Assays in Context: From 2D to 3D and In Situ Analysis.Annual review of analytical chemistry (Palo Alto, Calif.) · 2026
    Review
  7. Article
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  12. Review
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  15. Review
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  18. Article
  19. A Rapid and Modular Nanobody Assay for Plug-and-Play Antigen Detection.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

11 authors at 2 institutions in 2 countries.

Axel KlaessonDepartment of Pharmaceutical Biosciences, Pharmaceutical Cell Biology, Uppsala University, Uppsala, Sweden.
Karin GrannasDepartment of Pharmaceutical Biosciences, Pharmaceutical Cell Biology, Uppsala University, Uppsala, Sweden.
Tonge EbaiDepartment of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Johan HeldinDepartment of Pharmaceutical Biosciences, Pharmaceutical Cell Biology, Uppsala University, Uppsala, Sweden.ORCID 0000-0002-0915-5303
Björn KoosDepartment of Systemic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany.
Mattias LeinoDepartment of Pharmaceutical Biosciences, Pharmaceutical Cell Biology, Uppsala University, Uppsala, Sweden.
Doroteya RaykovaDepartment of Pharmaceutical Biosciences, Pharmaceutical Cell Biology, Uppsala University, Uppsala, Sweden.
Johan OelrichDepartment of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Linda ArngårdenDepartment of Pharmaceutical Biosciences, Pharmaceutical Cell Biology, Uppsala University, Uppsala, Sweden.
Ola SöderbergDepartment of Pharmaceutical Biosciences, Pharmaceutical Cell Biology, Uppsala University, Uppsala, Sweden. ola.soderberg@farmbio.uu.se.ORCID 0000-0003-2883-1925
Ulf LandegrenDepartment of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden. ulf.landegren@igp.uu.se.ORCID 0000-0002-7820-1000
Uppsala University · SEMax Planck Institute of Molecular Physiology · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

We have redesigned probes for in situ proximity ligation assay (PLA), resulting in more efficient localized detection of target proteins. In situ PLA depends on recognition of target proteins by pairs of antibody-oligonucleotide conjugates (PLA probes), which jointly give rise to DNA circles that template localized rolling circle amplification reactions. The requirement for dual recognition of the target proteins improves selectivity by ignoring any cross-reactivity not shared by the antibodies, and it allows detection of protein-protein interactions and post-translational modifications. We herein describe an improved design of the PLA probes -UnFold probes - where all elements required for formation of circular DNA strands are incorporated in the probes. Premature interactions between the UnFold probes are prevented by including an enzymatic "unfolding" step in the detection reactions. This allows DNA circles to form by pairs of reagents only after excess reagents have been removed. We demonstrate the performance of UnFold probes for detection of protein-protein interactions and post-translational modifications in fixed cells and tissues, revealing considerably more efficient signal generation. We also apply the UnFold probes to detect IL-6 in solution phase after capture on solid supports, demonstrating increased sensitivity over both normal sandwich enzyme-linked immunosorbent assays and conventional PLA assays.

Indexed as

Antibodies, ImmobilizedBase Sequencebeta CateninCadherinsCell LineDNA, CircularFluorescent DyesHumansMicroscopy, FluorescenceNucleic Acid ConformationOligonucleotidesProtein Interaction MappingProtein Processing, Post-TranslationalProteinsSkinAntibodies, Immobilizedbeta CateninCadherinsDNA, CircularFluorescent DyesOligonucleotidesProteins

Identifiers

PMID29599435
PMCPMC5876389
OpenAlexW2805205271

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.