A bioinformatic single-cell and structure-informed framework identifies a baicalin–CA2–keratinocyte state axis in atopic dermatitis

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Publication Details

Journal
PLoS ONE
Published
2026-09-11
DOI
https://doi.org/10.1371/journal.pone.0356174
Primary Topic
Dermatology and Skin Diseases
Type
article
Field-Weighted Citation Impact
0.00
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article

A bioinformatic single-cell and structure-informed framework identifies a baicalin–CA2–keratinocyte state axis in atopic dermatitis

Guilin Zhou, Boyan Yang, Jun Dai
PLoS ONE
Dermatology and Skin Diseases
article

A bioinformatic single-cell and structure-informed framework identifies a baicalin–CA2–keratinocyte state axis in atopic dermatitis

Guilin Zhou, Boyan Yang, Jun Dai
article en

Abstract

Atopic dermatitis (AD) is characterized by a self-reinforcing loop between epidermal barrier dysfunction and type 2-skewed inflammation; yet the most perturbed keratinocyte states and actionable epidermal targets remain incompletely defined. We integrated pharmacogenomic target mining, complementary machine-learning feature selection (LASSO and SVM-RFE), single-cell state-resolved perturbation analyses (Augur and scDist), and structure-based molecular modeling (molecular docking, MD simulation, and MM-PBSA free energy calculation) to prioritize candidate targets of baicalin in AD. CA2 emerged as a convergent epidermal candidate; scRNA-seq analyses localized CA2-associated transcriptional differences to keratinocytes, with the keratinocyte compartment exhibiting the disease-associated strongest separability and transcriptomic distance, accompanied by enrichment of metabolic reprogramming, epithelial junction and barrier remodeling, and proliferative quiescence gene programs. Structure-based evaluation supported a computationally plausible baicalin-CA2 interaction, with an estimated MM-PBSA binding free energy of -22.082 kcal/mol. Collectively, these findings nominate a computationally supported "baicalin-CA2-Kcs9" axis as a hypothesis-generating framework for epidermal stratification and experimental prioritization in AD.

PLoS ONEVol. 21(9)
Fourth People's Hospital of Sichuan Province (CN), Second People’s Hospital of Yibin (CN)
Affordable and clean energy
Openalex Percentile: Top 9%
Dermatology and Skin Diseases
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