Integrative systems biology framework discovers common gene regulatory signatures in mechanistically distinct inflammatory skin diseases

• Published in: NPJ systems biology and applications Vol. 11; no. 1; pp. 21 - 15
• Main Authors: Mishra, Bharat, Gou, Yifei, Tan, Zhengzhi, Wang, Yiqing, Hu, Getian, Athar, Mohammad, Mukhtar, M. Shahid
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 27.02.2025; Nature Publishing Group; Nature Portfolio
• Subjects: 631/114; 631/208/2490; 631/337; 631/553/2490; Acne; Atopic dermatitis; Bioinformatics; Biology; Biomedical and Life Sciences; Chronic illnesses; Computational Biology - methods; Computational Biology/Bioinformatics; Computer Appl. in Life Sciences; Datasets; Dermatitis; Dermatitis, Atopic - genetics; Drug development; Gene Expression Profiling; Gene Regulatory Networks; Genes; Hidradenitis Suppurativa - genetics; Humans; Ikaros Transcription Factor - genetics; Ikaros Transcription Factor - metabolism; Inflammation - genetics; Life Sciences; Molecular modelling; Pathogenesis; Proteins; Psoriasis; Psoriasis - genetics; Rosacea; Skin diseases; Skin Diseases - genetics; Systems Biology; Systems Biology - methods; Therapeutic applications; Therapeutic targets; Transcriptome; Transcriptomics
• ISSN: 2056-7189; 2056-7189
• DOI: 10.1038/s41540-025-00498-x

More than 20% of the population across the world is affected by non-communicable inflammatory skin diseases including psoriasis, atopic dermatitis, hidradenitis suppurativa, rosacea, etc. Many of these chronic diseases are painful and debilitating with limited effective therapeutic interventions. This study aims to identify common regulatory pathways and master regulators that regulate the molecular pathogenesis of inflammatory skin diseases. We designed an integrative systems biology framework to identify the significant regulators across several diseases. Network analytics unraveled 55 high-value proteins as significant regulators in molecular pathogenesis which can serve as putative drug targets for more effective treatments. We identified IKZF1 as a shared master regulator in hidradenitis suppurativa, atopic dermatitis, and rosacea with known disease-derived molecules for developing efficacious combinatorial treatments for these diseases. The proposed framework is very modular and indicates a significant path of molecular mechanism-based drug development from complex transcriptomics data and other multi-omics data.