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Puccio, S.

Publications and source records attributed to Puccio, S..

2 recordsLinked to original sources

Unveiling the Power of High-Dimensional Cytometry Data with cyCONDOR

High-dimensional cytometry (HDC) is a powerful technology for studying single-cell phenotypes in complex biological systems. Although technological developments and affordability have made HDC broadly available in recent years, technological advances were not coupled with an adequate development of analytical methods that can take full advantage of the complex data generated. While several analytical platforms and bioinformatics tools have become available for the analysis of HDC data, these are either web-hosted with limited scalability or designed for expert computational biologists, making their use unapproachable for wet lab scientists. Additionally, end-to-end HDC data analysis is further hampered due to missing unified analytical ecosystems, requiring researchers to navigate multiple platforms and software packages to complete the analysis. To bridge this data analysis gap in HDC we developed cyCONDOR, an easy-to-use computational framework covering not only all essential steps of cytometry data analysis but also including an array of downstream functions and tools to expand the biological interpretation of the data. The comprehensive suite of features of cyCONDOR, including guided pre-processing, clustering, dimensionality reduction, and machine learning algorithms, facilitates the seamless integration of cyCONDOR into clinically relevant settings, where scalability and disease classification are paramount for the widespread adoption of HDC in clinical practice. Additionally, the advanced analytical features of cyCONDOR, such as pseudotime analysis and batch integration, provide researchers with the tools to extract deeper insights from their data. We used cyCONDOR on a variety of data from different tissues and technologies demonstrating its versatility to assist the analysis of high dimensionality data from preprocessing to biological interpretation.

bioinformatics↗

Multimodal single-cell profiling of intrahepatic cholangiocarcinoma defineshyperactivated Tregs as a potential therapeutic target

The quality of the immune infiltrate of intrahepatic cholangiocarcinoma (iCCA), a rare, yet aggressive tumor of the biliary tract, remains poorly characterized, limiting development of successful immunotherapies. We used high-dimensional flow cytometry to characterise the T cell and myeloid compartments of iCCA comparing these with their tumor-free peritumoral and circulating counterparts. We found poor infiltration of putative tumor-specific CD39+ CD8+ T cells accompanied by abundant infiltration of hyperactivated CD4+ regulatory T cells (Tregs), whose frequency in relation to that of CD4+ CD69+ T cells and conventional type 2 dendritic cells was associated with poor prognosis. Single-cell RNA-sequencing identified an altered network of transcription factors in iCCA-infiltrating compared to peritumoral T cells, suggesting reduced effector functions by tumor-infiltrating CD8+ T cells and enhanced immunosuppression by CD4+ Tregs. Specifically, we found that expression of mesenchyme homeobox 1 (MEOX1) was highly enriched in tumor-infiltrating Tregs, and demonstrated that MEOX1 overexpression is sufficient to reprogram circulating precursors to acquire the transcriptional and epigenetic landscape of tumorinfiltrating Tregs. Interfering with hyperactivated Tregs should be thus explored to enhance antitumor immunity in iCCA.

immunology↗