Evidence map›Paper›PMID 37652024›Full record

ArticleCell chemical biology2023

Target deconvolution with matrix-augmented pooling strategy reveals cell-specific drug-protein interactions.

Hongchao Ji, Xue Lu, Shiji Zhao, Qiqi Wang, Bin Liao, Ludwig G Bauer, Kilian V M Huber, Ray Luo, Ruijun Tian, Chris Soon Heng Tan

Open access · greenAbstract read
In one paragraph

Article in Cell chemical biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
3.6field-weighted citation impact, top 6% 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

12 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.

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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 3 institutions in 3 countries.

Hongchao JiDepartment of Chemistry and Research Center for Chemical Biology and Omics Analysis, College of Science, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China PR; Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Genome Analysis Laboratory of the Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518120, China.
Xue LuDepartment of Chemistry and Research Center for Chemical Biology and Omics Analysis, College of Science, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China PR.
Shiji ZhaoDepartment of Molecular Biology and Biochemistry, Department of Chemical and Biomolecular Engineering, Department of Materials Science and Engineering, Department of Biomedical Engineering, University of California, Irvine, Irvine, CA 92697, USA.
Qiqi WangDepartment of Chemistry and Research Center for Chemical Biology and Omics Analysis, College of Science, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China PR.
Bin LiaoDepartment of Chemistry and Research Center for Chemical Biology and Omics Analysis, College of Science, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China PR.
Ludwig G BauerCentre for Medicines Discovery, Nuffield Department of Medicine, OX3 7FZ Oxford, UK; Target Discovery Institute, Nuffield Department of Medicine, OX3 7FZ Oxford, UK.
Kilian V M HuberCentre for Medicines Discovery, Nuffield Department of Medicine, OX3 7FZ Oxford, UK; Target Discovery Institute, Nuffield Department of Medicine, OX3 7FZ Oxford, UK.
Ray LuoDepartment of Molecular Biology and Biochemistry, Department of Chemical and Biomolecular Engineering, Department of Materials Science and Engineering, Department of Biomedical Engineering, University of California, Irvine, Irvine, CA 92697, USA.
Ruijun TianDepartment of Chemistry and Research Center for Chemical Biology and Omics Analysis, College of Science, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China PR.
Chris Soon Heng TanDepartment of Chemistry and Research Center for Chemical Biology and Omics Analysis, College of Science, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China PR. Electronic address: christan@sustech.edu.cn.
Southern University of Science and Technology · CNNuffield Orthopaedic Centre · GBUniversity of California, Irvine · US

Funding

Multi-scaled Modeling of Electrostatic and Polarization Effects in BiomoleculesR35GM130367 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI RAY LUO · 2019 to 2026
$3.0M
NIGMS NIH HHS R35 GM130367
6 · The paper itself

Abstract

Target deconvolution is a crucial but costly and time-consuming task that hinders large-scale profiling for drug discovery. We present a matrix-augmented pooling strategy (MAPS) which mixes multiple drugs into samples with optimized permutation and delineates targets of each drug simultaneously with mathematical processing. We validated this strategy with thermal proteome profiling (TPP) testing of 15 drugs concurrently, increasing experimental throughput by 60x while maintaining high sensitivity and specificity. Benefiting from the lower cost and higher throughput of MAPS, we performed target deconvolution of the 15 drugs across 5 cell lines. Our profiling revealed that drug-target interactions can differ vastly in targets and binding affinity across cell lines. We further validated BRAF and CSNK2A2 as potential off-targets of bafetinib and abemaciclib, respectively. This work represents the largest thermal profiling of structurally diverse drugs across multiple cell lines to date.

Indexed as

ProteomeProteomicsCell LineDrug DiscoveryPyrimidinesProteomePyrimidinescellular thermal shift assaychemical biologychemical proteomicsdrug developmentdrug discoveryprotein mass spectrometryproteome thermal profilingtarget deconvolution

Identifiers

PMID37652024
PMCPMC10840709
OpenAlexW4386304573

What OpenQuestion holds

Textmetadata
LicenceTDM
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.