ViCEKb: Vitiligo-linked Chemical Exposome Knowledgebase

Vitiligo is a complex disease wherein the environmental factors, in conjunction with the underlying genetic predispositions, trigger the autoimmune destruction of melanocytes, ultimately leading to depigmented patches on the skin. While genetic factors have been extensively studied, the knowledge on environmental triggers remains sparse and less understood. To address this knowledge gap, we present the first comprehensive knowledgebase of vitiligo-triggering chemicals namely, Vitiligo-linked Chemical Exposome Knowledgebase (ViCEKb). ViCEKb involves an extensive and systematic manual effort in curation of published literature and subsequent compilation of 113 unique chemical triggers of vitiligo. ViCEKb standardizes various chemical information, and categorizes the chemicals based on their evidences and sources of exposure. Importantly, ViCEKb contains a wide range of metrics necessary for different toxicological evaluations. Notably, we observed that ViCEKb chemicals are present in a variety of consumer products. For instance, Propyl gallate is present as a fragrance substance in various household products, and Flutamide is used in medication to treat prostate cancer. These two chemicals have the highest level of evidence in ViCEKb, but are not regulated for their skin sensitizing effects. Furthermore, an extensive cheminformatics-based investigation revealed that ViCEKb chemical space is structurally diverse and comprises unique chemical scaffolds in comparison with skin specific regulatory lists. For example, Neomycin and 2,3,5-Triglycidyl-4-aminophenol have unique chemical scaffolds and the highest level of evidence in ViCEKb, but are not regulated for their skin sensitizing effects. Finally, a transcriptomics-based analysis of ViCEKb chemical perturbations in skin cell samples highlighted the commonality in their linked biological processes. Overall, we present the first comprehensive effort in compilation and exploration of various chemical triggers of vitiligo. We believe such a resource will enable in deciphering the complex etiology of vitiligo and aid in the characterization of human chemical exposome. ViCEKb is freely available for academic research at: https://cb.imsc.res.in/vicekb.