Spatial Transcriptomics and Gene Networks for Unravelling Pathogenic Mechanisms: Atopic Dermatitis Case Study

Abstract

Spatial transcriptomics is an emerging molecular profiling technique that uniquely characterizes the simultaneous analysis of gene activity and spatial mapping within a tissue sample. It provides in-depth information on gene expression in tissue microenvironments along with the spatial distribution of genes within cells. It has two types of techniques which are imaging-based and sequencing-based. In this study, Visium spatial gene expression is used which is a component of the 10x Genomics platform. It is a cutting-edge molecular profiling tool that uses messenger RNA to classify tissues while enabling transcriptome mapping. In this study, atopic dermatitis which is commonly known as eczema is taken as a case study to identify the spatial distribution of genes. It is a chronic disease and causes inflammation, itching, and dryness, in the skin. It is most commonly found in young children, but it can occur at any age. To study further about atopic dermatitis a comparative analysis was performed between the individuals with six healthy, seven lesional, and six non-lesional skin types. Using Scanpy which is a tool of spatial transcriptomics the marker genes for each state were then identified. For further analysis, the unique and common marker genes between all the states of skin type were found. The common genes were then used to identify the top 10 hub genes across all conditions to gain new insights into the spatial distribution and pathway involvement of important genes. These hub genes were then searched with pathway analysis in the top 10 significant pathways of both the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome. It was found that the gene LOR known as loricrin was in the list of top 10 hub genes among all the conditions, and was not included in both pathway databases. This study aims to find the association of the LOR gene with atopic dermatitis. Moreover, trajectory analysis of common and unique genes was performed to understand the mechanisms of transition between various skin states, providing a thorough understanding of their involvement in the progression of atopic dermatitis.