XYcellAtlas: a cell-type- and spatial-resolved pan-cancer atlas of sex-biased and Y chromosome loss-associated molecular signatures

Abstract

Sex is a critical determinant of cancer susceptibility, clinical prognosis, and therapeutic response. Sex chromosome aberrations, particularly somatic loss of the Y chromosome (LOY) in male malignancies, exert profound impacts on transcriptional regulation, tumor immune microenvironment remodeling, and malignant progression, highlighting an urgent demand for comprehensive integration of single–cell and spatial omics profiles dissecting sex-biased and LOY landscapes across human cancers. Here, we developed XYcellAtlas (http://www.xycellatlas.top/), an integrative database for integration and multidimensional visualization of sex disparities and LOY features across human tissues at single-cell transcriptomic, epigenomic, and spatial-transcriptomic resolutions. This resource aggregates data from 6764 patient samples covering 18 cancer types, eight precancerous lesions, and 21 tissue origins, encompassing over 25.8 million single cells and one million spatial-transcriptomic spots. Leveraging random forest classifiers trained on normal tissue datasets, XYcellAtlas quantifies cell-type-specific LOY frequencies across cell types. Furthermore, it systematically catalogs sex-biased and LOY-associated molecular alterations, including differentially expressed genes, chromatin peaks, core transcription factors, as well as their functional annotations and dysregulatory signatures within malignant cells and the tumor microenvironment. In summary, XYcellAtlas provides a unified, all-in-one analytical platform enabling researchers to query, inspect, quantify, and visualize sex-associated and LOY-derived multi-omics features underlying tumor evolutionary processes.