Advanced whole transcriptome sequencing and artificial intelligence/machine learning (AI/ML) in imiquimod-induced psoriasis-like inflammation of human keratinocytes

Authors

Lii-Tzu Wu, Department of Microbiology, School of Medicine, China Medical University, Taichung, Taiwan.
Shih-Chang Tsai, Department of Biological Science and Technology, China Medical University, Taichung, Taiwan.
Tsung‑Jung Ho, Integration Center of Traditional Chinese and Modern Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan,
Hao-Ping Chen, Integration Center of Traditional Chinese and Modern Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
Yu-Jen Chiu, Division of Plastic and Reconstructive Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
Yan-Ru Peng, Department of Ophthalmology, Taipei City Hospital, Taipei, Taiwan
Ting-Yuan Liu, Million-Person Precision Medicine Initiative, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
Yu‑Ning Juan, Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan.
Jai-Sing Yang, Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan.Follow
Fuu-Jen Tsai, Million-Person Precision Medicine Initiative, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.Follow

Abstract

Introduction: Although the HaCaT keratinocyte model has been used in previous research to study the effects of anti-psoriatic agents, there is still a lack of comprehensive understanding of the mechanism of imiquimod (IMQ)-induced proliferation and signal transduction in psoriasis-like keratinocytes.

Objectives: This study aimed to investigate the molecular mechanisms and pathways associated with psoriasis-like inflammation caused by IMQ in human keratinocytes.

Materials and Methods: HaCaT cells were exposed to different concentrations of IMQ to induce inflammation similar to that observed in psoriasis. Cell viability was evaluated using the MTT assay and cell morphology was examined using phase-contrast microscopy. Gene expression profiles were analyzed through whole transcriptome sequencing, followed by bio-informatics network analysis using IPA software. The GSEA was conducted with the aim of identifying enriched pathways. The expression of key cytokines IL-6 and TNF-α was confirmed by QPCR. Artificial intelligence/machine learning (AI/ML) algorithms were used to predict potential diseases and phenotypes associated with the observed gene profiles.

Results: IMQ treatment demonstrated a substantial positive impact on cell survival without any detectable alterations in the morphology of HaCaT cells. A comprehensive analysis of the entire set of transcribed genes identified 513 genes that exhibited differential expression. Bioinformatics analysis revealed key pathways associated with immune response, cellular proliferation, and cytokine signaling. GSEA identified significant enrichment in the IFN-γ response and JAK-STAT signaling pathways. QPCR analysis confirmed the increased mRNA expression levels of IL-6 and TNF-α in cells treated with IMQ. AI/ML algorithms have identified potential correlations with diseases, such as multiple sclerosis, lympho-proliferative malignancy, and autoimmune disorders.

Conclusion: Our results highlight the importance of specific genes and pathways, particularly those associated with IFN-γ pathway and IL-6/JAK-STAT signaling. AI/ML predictions indicate potential associations with various diseases and provide valuable insights for the development of novel therapeutic approaches for psoriasis and related disorders.

Recommended Citation

Wu, Lii-Tzu; Tsai, Shih-Chang; Ho, Tsung‑Jung; Chen, Hao-Ping; Chiu, Yu-Jen; Peng, Yan-Ru; Liu, Ting-Yuan; Juan, Yu‑Ning; Yang, Jai-Sing; and Tsai, Fuu-Jen (2024) "Advanced whole transcriptome sequencing and artificial intelligence/machine learning (AI/ML) in imiquimod-induced psoriasis-like inflammation of human keratinocytes," BioMedicine: Vol. 14 : Iss. 4 , Article 3.
DOI: 10.37796/2211-8039.1468

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.