WebCSEA: web-based cell-type-specific enrichment analysis of genes
Yulin Dai, Ruifeng Hu, Andi Liu, Kyung Serk Cho, Astrid M. Manuel, Xiaoyang Li, Xianjun Dong, Peilin Jia, Zhongming Zhao
Abstract
Human complex traits and common diseases show tissue- and cell-type- specificity. Recently, single-cell RNA sequencing (scRNA-seq) technology has successfully depicted cellular heterogeneity in human tissue, providing an unprecedented opportunity to understand the context-specific expression of complex trait-associated genes in human tissue-cell types (TCs). Here, we present the first web-based application to quickly assess the cell-type-specificity of genes, named Web-based Cell-type Specific Enrichment Analysis of Genes (WebCSEA, available at https://bioinfo.uth.edu/webcsea/). Specifically, we curated a total of 111 scRNA-seq panels of human tissues and 1,355 TCs from 61 different general tissues across 11 human organ systems. We adapted our previous decoding tissue-specificity (deTS) algorithm to measure the enrichment for each tissue-cell type (TC). To overcome the potential bias from the number of signature genes between different TCs, we further developed a permutation-based method that accurately estimates the TC-specificity of a given inquiry gene list. WebCSEA also provides an interactive heatmap that displays the cell-type specificity across 1355 human TCs, and other interactive and static visualizations of cell-type specificity by human organ system, developmental stage, and top-ranked tissues and cell types. In short, WebCSEA is a one-click application that provides a comprehensive exploration of the TC-specificity of genes among human major TC map.