Multiscale analysis of acne connects molecular subnetworks with disease status

Abstract

Acne vulgaris affects millions of individuals and can lead to psychosocial impairment as well as permanent scarring. Previous studies investigating acne pathogenesis have either examined a targeted set of biological parameters in a modest-sized cohort or carried out high-throughput assays on a small number of samples. To develop a more comprehensive understanding of acne pathophysiology, we conducted an in-depth multi-omic study of 56 acne patients and 20 individuals without acne. We collected whole blood, skin punch biopsies, microbiota from skin follicles, and relevant clinical measurements to understand how multiple factors contribute to acne. We provide an integrative analysis of multi-omics data that results in a molecular network of acne. Comparisons of lesional and non-lesional skin highlighted multiple biological processes, including immune cell and inflammatory responses, response to stress, T cell activation, lipid biosynthesis, fatty acid metabolism, keratinocytes, antimicrobial activity, epithelial cell differentiation, and response to wounding, that are differentially altered in acne lesions compared to non-lesions. Our results suggest baseline differences in the skin that may predispose individuals to develop acne. These datasets and findings offer a framework for new target identification and reference for future studies.3

Comparative transcriptome analysis of acne vulgaris, rosacea, and hidradenitis suppurativa supports high‐dose dietary zinc as a therapeutic agent

“…Through a comprehensive multi-omic analysis of acne patients' lesion and non-lesion skin samples, researchers identified a differential gene expression profile enriched in keratinization, immune response, and lipid metabolism and biosynthesis. 3 Similarly, a transcriptome analysis of rosacea patients' lesion samples indicated a Th1/Th17 polarized inflammation profile and significant macrophage infiltration across all rosacea subtypes. 4 Likewise, a study on HS showcased varying gene expression in immune response, antimicrobial response, and cell differentiation within follicular and epidermal keratinocytes.…”

“…We collected three transcriptomic datasets, each for the three diseases from NCBI's Gene Expression Omnibus (Acne vulgaris: GSE6475; PPR: GSE65914; HS: GSE148027; Figure S1a). [3][4][5] Eight additional datasets (Acne vulgaris: GSE53795, GSE108110; PPR: Dataset 1 and Dataset 2; HS: GSE122592; GSE213761; GSE154773; GSE72702) were also utilised for validation. [6][7][8][9][10][11][12][13] Figure 1A illustrates the project's overarching design: conducting bioinformatic analyses on the datasets to identify differentially expressed genes (DEGs), followed by comparing these DEGs and enriched pathways across the three diseases to pinpoint those shared and unique.…”

Comparative Transcriptome Analysis of Acne vulgaris, Rosacea, and Hidradenitis Suppurativa Supports High Dose Dietary Zinc as a Therapeutic Agent

“…The application of omics technologies has substantially deepened our grasp of the molecular changes that drives skin disorders. Through a comprehensive multi-omic analysis of acne patients’ lesion and non- lesion skin samples, researchers identified a differential gene expression profile enriched in keratinization, immune response, and lipid metabolism and biosynthesis (Hall et al 2019). Similarly, a transcriptome analysis of rosacea patients’ lesion samples indicated a Th1/Th17 polarized inflammation profile and significant macrophage infiltration across all rosacea subtypes (Buhl et al 2015).…”

“…We collected three transcriptomic datasets, each for the three diseases from NCBI’s Gene Expression Omnibus (Acne vulgaris: GSE6475; PPR: GSE65914; HS: GSE148027; Supplementary Fig. 1a) (Buhl et al 2015; Hall et al 2019; Zouboulis et al 2020). Eight additional datasets (Acne vulgaris: GSE53795, GSE108110; PPR: Dataset 1 and Dataset 2; HS: GSE122592; GSE213761; GSE154773; GSE72702) were also utilized for validation (Kelhälä et al 2014; Carlavan et al 2018; Shih et al 2020; Medgyesi et al 2020; Witte-Händel et al 2019; Lowe et al 2020; Gudjonsson et al 2020; Blok et al 2016).…”

Transcriptomics Analysis Indicates Trifarotene Reverses Acne-Related Gene Expression Changes

“…Acne vulgaris is a chronic inflammatory skin condition that develops from a combination of four critical factors: (i) increased sebum production, (ii) abnormal keratinization and cornification of the sebaceous follicular duct, (iii) colonization of the hair follicles by microbes-putatively Cutibacterium, and (iv) complex inflammatory mechanisms that involve both innate and acquired immunity (1,2). Trifarotene is the first topical retinoid molecule to be marketed in almost two decades, and it has demonstrated good efficacy in treating facial and truncal acne (3).…”