Unraveling lncRNA Diversity at a Single Cell Resolution and in a Spatial Context across Different Cancer Types

Abstract

Long non-coding RNAs (lncRNAs) play pivotal roles in gene regulation and disease, including cancer. Overcoming the limitations of lncRNA analysis with bulk data, we analyzed single-cell and spatial transcriptomics data to uncover 354937 novel lncRNAs and their functions across 13 cancer types. LncRNA functions were assessed by identifying their cell-type specificity and distinct spatial distributions across different tissue regions. First, lncRNAs were computationally validated by comparing to existing databases, and experimentally validated using spatial long read sequencing methods. Further, genome-wide computation of spatial-autocorrelation identified coexpression of lncRNAs with cancer-associated protein coding genes across the tissue. Additionally, genomic co-localization of lncRNAs with regulatory features and disease-associated genetic variants suggest possible functional association. The identified lncRNAs were analyzed for responses to immunotherapy and prognostic value, revealing cancer-outcome associated lncRNAs. We have made this novel resource available as an open website ‘SPanC-Lnc’ hosted on AWS cloud to serve as a pan-cancer atlas of single cell- and spatially-resolved lncRNAs. These can complement established biomarkers because they reflect the unique characteristics of specific cell populations within tumors, offering new insights into disease progression and treatment response.