Lun, J. H. | Search bioRxiv

bioRxiv2025

Benchmarking cell-type deconvolution in cross-platform transcriptomic data

BackgroundTranscriptomic data from diverse measurement technologies are widely used to study tissue heterogeneity. Cell-type deconvolution, which resolves mixed transcriptomic signals into cellular components, is a key analytical approach. However, achieving accurate deconvolution across platforms remains challenging due to platform-specific experimental and technological biases. ResultsWe systematically benchmarked deconvolution performance using real-world cross-platform datasets and simulated data modeling distinct technological features. Our analyses provide practical guidelines for experimental design and promote more robust and comparable cross-platform transcriptomic analyses. ConclusionLog-normal regression methods such as SpatialDecon demonstrated the most reliable and consistent performance across both simulated and experimental settings, establishing a robust framework for accurate cross-platform transcriptomic deconvolution. Moreover, our results highlight potential caveats in deconvolution predictions arising from specific experimental conditions, providing guidance for more informed experimental design and interpretation Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=60 SRC="FIGDIR/small/690141v1_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@585cbdorg.highwire.dtl.DTLVardef@13088c7org.highwire.dtl.DTLVardef@163ea75org.highwire.dtl.DTLVardef@b5ccf7_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2024

Glioma-associated tertiary lymphoid structures are sites of lymphocyte clonal expansion and plasma cell formation

Adult-type diffuse gliomas, the most common primary brain tumors, pose significant clinical challenges due to limited treatment options, restricted anti-tumor immune response and dismal patient prognosis. In this study, we elucidate the immunological function and clinical relevance of intra-tumoral tertiary lymphoid structures (TLS) in adaptive anti-glioma immunity. We conducted a comprehensive, unbiased analysis of lymphoid aggregation in 642 gliomas using a multi-modal approach that combines RNA sequencing with spatial transcriptome and proteome profiling. Our findings reveal that TLS are present in 15% of tumors and correlate with improved overall survival. Gliomas with TLS exhibit a remodeled perivascular space, marked by transcriptional upregulation and spatial redistribution of collagens associated with barrier functions. Furthermore, we demonstrate that TLS maturation into sites of dynamic adaptive immune responses, characterized by clonal T and B cell expansion and IgA+ and IgG+ plasma-cell formation, is driven by efficient early T cell recruitment to the perivascular space.

immunology↗