Evidence map›Paper›PMID 38854075›Full record

ArticlebioRxiv : the preprint server for biology2024

Molecular Display of the Animal Meta-Venome for Discovery of Novel Therapeutic Peptides.

Meng-Hsuan Hsiao, Yang Miao, Zixing Liu, Konstantin Schütze, Nathachit Limjunyawong, Daphne Chun-Che Chien, Wayne Denis Monteiro, Lee-Shin Chu, William Morgenlander, Sahana Jayaraman and 6 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors.

Meng-Hsuan HsiaoInstitute for Cell Engineering, Division of Immunology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Yang MiaoInstitute for Cell Engineering, Division of Immunology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Zixing LiuInstitute for Cell Engineering, Division of Immunology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Konstantin SchützeSchool of Biological Sciences, Seoul National University, Seoul, South Korea.
Nathachit LimjunyawongThe Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Daphne Chun-Che ChienThe Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Wayne Denis MonteiroInstitute for Cell Engineering, Division of Immunology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Lee-Shin ChuDepartment of Chemical and Biomolecular Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
William MorgenlanderInstitute for Cell Engineering, Division of Immunology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Sahana JayaramanInstitute for Cell Engineering, Division of Immunology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Sung-Eun JangSchool of Biological Sciences, Seoul National University, Seoul, South Korea.
Jeffrey J GrayDepartment of Chemical and Biomolecular Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.ORCID 0000-0001-6380-2324
Heng ZhuDepartment of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Xinzhong DongThe Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Martin SteineggerSchool of Biological Sciences, Seoul National University, Seoul, South Korea.ORCID 0000-0001-8781-9753
H Benjamin LarmanInstitute for Cell Engineering, Division of Immunology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Funding

Design and Analysis of Displayed PeptidomesR01GM136724 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI LARMAN, HARRY BENJAMIN, RUCZINSKI, INGO · 2020 to 2023
$1.9M
NIGMS NIH HHS R01 GM136724
6 · The paper itself

Abstract

Animal venoms, distinguished by their unique structural features and potent bioactivities, represent a vast and relatively untapped reservoir of therapeutic molecules. However, limitations associated with extracting or expressing large numbers of individual venoms and venom-like molecules have precluded their therapeutic evaluation via high throughput screening. Here, we developed an innovative computational approach to design a highly diverse library of animal venoms and "metavenoms". We employed programmable M13 hyperphage display to preserve critical disulfide-bonded structures for highly parallelized single-round biopanning with quantitation via high-throughput DNA sequencing. Our approach led to the discovery of Kunitz type domain containing proteins that target the human itch receptor Mas-related G protein-coupled receptor X4 (MRGPRX4), which plays a crucial role in itch perception. Deep learning-based structural homology mining identified two endogenous human homologs, tissue factor pathway inhibitor (TFPI) and serine peptidase inhibitor, Kunitz type 2 (SPINT2), which exhibit agonist-dependent potentiation of MRGPRX4. Highly multiplexed screening of animal venoms and metavenoms is therefore a promising approach to uncover new drug candidates.

Indexed as

database miningitch receptorligand discoveryphage displayvenom

Identifiers

PMID38854075
PMCPMC11160688

What OpenQuestion holds

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LicenceCC BY-ND
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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.