Evidence map›Paper›PMID 33986742›Full record

ArticleFrontiers in immunology2021

Protein-Based Immunome Wide Association Studies (PIWAS) for the Discovery of Significant Disease-Associated Antigens.

Winston A Haynes, Kathy Kamath, Rebecca Waitz, Patrick S Daugherty, John C Shon

Open access · goldAbstract readValidation Study
In one paragraph

Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.5field-weighted citation impact, top 11% 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

19 citing papers in PubMed, 25 citations in OpenAlex.

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  15. medRxiv : the preprint server for health sciences · 2021
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  19. Autoantibody Landscape in Patients with Advanced Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020
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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

5 authors at 1 institution in 1 country.

Winston A HaynesSerimmune, Inc., Santa Barbara, CA, United States.
Kathy KamathSerimmune, Inc., Santa Barbara, CA, United States.
Rebecca WaitzSerimmune, Inc., Santa Barbara, CA, United States.
Patrick S DaughertySerimmune, Inc., Santa Barbara, CA, United States.
John C ShonSerimmune, Inc., Santa Barbara, CA, United States.
Serimmune (United States) · US

Funding

INTERNATIONAL RESEARCH REGISTRY NETWORK FOR SJOGERNS SYNDROME-268032636N01DE032636 · NIDCR · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GREENSPAN, JOHN · 2005 to 2006
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NIDCR NIH HHS N01 DE032636
6 · The paper itself

Abstract

Identification of the antigens associated with antibodies is vital to understanding immune responses in the context of infection, autoimmunity, and cancer. Discovering antigens at a proteome scale could enable broader identification of antigens that are responsible for generating an immune response or driving a disease state. Although targeted tests for known antigens can be straightforward, discovering antigens at a proteome scale using protein and peptide arrays is time consuming and expensive. We leverage Serum Epitope Repertoire Analysis (SERA), an assay based on a random bacterial display peptide library coupled with next generation sequencing (NGS), to power the development of Protein-based Immunome Wide Association Study (PIWAS). PIWAS uses proteome-based signals to discover candidate antibody-antigen epitopes that are significantly elevated in a subset of cases compared to controls. After demonstrating statistical power relative to the magnitude and prevalence of effect in synthetic data, we apply PIWAS to systemic lupus erythematosus (SLE, n=31) and observe known autoantigens, Smith and Ribosomal protein P, within the 22 highest scoring candidate protein antigens across the entire human proteome. We validate the magnitude and location of the SLE specific signal against the Smith family of proteins using a cohort of patients who are positive by predicate anti-Sm tests. To test the generalizability of the method in an additional autoimmune disease, we identified and validated autoantigenic signals to SSB, CENPA, and keratin proteins in a cohort of individuals with Sjogren's syndrome (n=91). Collectively, these results suggest that PIWAS provides a powerful new tool to discover disease-associated serological antigens within any known proteome.

Indexed as

AutoimmunityImmunodominant EpitopesProteomeProteomicsAutoantibodiesAutoantigensCase-Control StudiesComputer SimulationDatabases, ProteinEnzyme-Linked Immunosorbent AssayHumansLupus Erythematosus, SystemicPeptide LibraryReproducibility of ResultsSerologic TestsSjogren's SyndromeAutoantibodiesAutoantigensImmunodominant EpitopesPeptide LibraryProteomeantigenbioinformatics & computational biologycomputational immunologyimmunology & inflammationimmunome

Identifiers

PMID33986742
PMCPMC8110919
OpenAlexW3158064763

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.