Evidence map›Paper›PMID 24222690›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2013

Antibody biomarker discovery through in vitro directed evolution of consensus recognition epitopes.

John T Ballew, Joseph A Murray, Pekka Collin, Markku Mäki, Martin F Kagnoff, Katri Kaukinen, Patrick S Daugherty

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
–field-weighted citation impact
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

16 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Review
  5. A MultipleBrain sciences · 2020
    Article
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  9. 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

7 authors.

John T BallewDepartment of Chemical Engineering and Center for Bioengineering, Biomolecular Science and Engineering Program, University of California, Santa Barbara, CA 93106.
Joseph A Murray
Pekka Collin
Markku Mäki
Martin F Kagnoff
Katri Kaukinen
Patrick S Daugherty

Funding

TL MOLECULES AND GAMMA-DELTA T CELLSP01DK035108 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ECKMANN, LARS · 1986 to 2013
$19.2M
EPIDEMIOLOGY OF CELIAC DISEASE--A POPULATION BASED STUDYR01DK057892 · NIDDK · MAYO CLINIC ROCHESTER · PI MURRAY, JOSEPH A · 2000 to 2010
$3.9M
Antibody Reprtoire Characterization in Celiac DiseaseR01AI092204 · NIAID · UNIVERSITY OF CALIFORNIA SANTA BARBARA · PI DAUGHERTY, PATRICK S · 2011 to 2015
$1.5M
Quantitative Serum Antibody Specificity Screening in Celiac DiseaseR21DK080395 · NIDDK · UNIVERSITY OF CALIFORNIA SANTA BARBARA · PI DAUGHERTY, PATRICK S · 2008 to 2009
$394k
NIAID NIH HHS AI09224NIAID NIH HHS R01 AI092204NIDDK NIH HHS DK057892NIDDK NIH HHS DK080395NIDDK NIH HHS DK35108NIDDK NIH HHS P01 DK035108NIDDK NIH HHS R01 DK057892NIDDK NIH HHS R21 DK080395
6 · The paper itself

Abstract

To enable discovery of serum antibodies indicative of disease and simultaneously develop reagents suitable for diagnosis, in vitro directed evolution was applied to identify consensus peptides recognized by patients' serum antibodies. Bacterial cell-displayed peptide libraries were quantitatively screened for binders to serum antibodies from patients with celiac disease (CD), using cell-sorting instrumentation to identify two distinct consensus epitope families specific to CD patients (PEQ and (E)/DxFV(Y)/FQ). Evolution of the (E)/DxFV(Y)/FQ consensus epitope identified a celiac-specific epitope, distinct from the two CD hallmark antigens tissue transglutaminase-2 and deamidated gliadin, exhibiting 71% sensitivity and 99% specificity (n = 231). Expansion of the first-generation PEQ consensus epitope via in vitro evolution yielded octapeptides QPEQAFPE and PFPEQxFP that identified ω- and γ-gliadins, and their deamidated forms, as immunodominant B-cell epitopes in wheat and related cereal proteins. The evolved octapeptides, but not first-generation peptides, discriminated one-way blinded CD and non-CD sera (n = 78) with exceptional accuracy, yielding 100% sensitivity and 98% specificity. Because this method, termed antibody diagnostics via evolution of peptides, does not require prior knowledge of pathobiology, it may be broadly useful for de novo discovery of antibody biomarkers and reagents for their detection.

Indexed as

AdultAgedAged, 80 and overAmino Acid SequenceAntibodiesBiomarkersCeliac DiseaseCohort StudiesDirected Molecular EvolutionDNA PrimersEpitopesFemaleFinlandFlow CytometryHumansMaleAntibodiesBiomarkersDNA PrimersEpitopesPeptidesProtein Glutamine gamma Glutamyltransferase 2TGM2 protein, human

Identifiers

PMID24222690
PMCPMC3845167

What OpenQuestion holds

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Registered trials

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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.