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Biology subjects

Notarbartolo, S.

Publications and source records attributed to Notarbartolo, S..

2 recordsLinked to original sources

CIA: a Cluster Independent Annotation method to investigate cell identities in scRNA-seq data

Single-cell RNA sequencing (scRNA-seq) has revolutionized our understanding of the transcriptional landscape of complex tissues, enabling the discovery of novel cell types and biological functions. However, the identification and classification of cells from scRNA-seq datasets remain significant challenges. To address this, we developed a new computational tool called CIA (Cluster Independent Annotation), which accurately identifies cell types across different datasets without requiring a fully annotated reference dataset or complex machine learning processes. Based on predefined cell type signatures, CIA provides a highly user-friendly and practical solution to functional annotation of single cells. Our results demonstrate that CIA outperforms other state-of-the-art approaches, while also having significantly lower computational running time. Overall, CIA simplifies the process of obtaining reproducible signature-based cell assignments that can be easily interpreted through graphical summaries providing researchers with a powerful tool to explore the complex transcriptional landscape of single cells. The CIA framework is implemented in both the Python and R programming languages, making it applicable to all main single-cell analysis frameworks, and it is available under the MIT license with its documentation at the following links: Python package: https://pypi.org/project/cia-python/ Python tutorial: https://cia-python.readthedocs.io/en/latest/tutorial/Cluster_Independent_Annotation.html R package and tutorial: https://github.com/ingmbioinfo/CIA_R

bioinformatics↗

The chromatin landscape of Th17 cells reveals mechanisms of diversification of regulatory and pro-inflammatory states

Th17 cells are a heterogenous cell population consisting of non-pathogenic Th17 cells (npTh17) that contribute to tissue homeostasis and pathogenic Th17 cells (pTh17) that are potent mediators of tissue inflammation. To reveal regulatory mechanisms underlying Th17 heterogeneity, we performed combined ATAC-seq and RNA-seq and discovered substantial differences in the chromatin landscape of npTh17 and pTh17 cells both in vitro and in vivo. Compared to other CD4+ T cell subsets, npTh17 cells share accessible chromatin programs with Tregs, and pTh17 cells have an intermediate profile spanning features of npTh17 cells and Th1 cells. Integrating single-cell ATAC-seq and single-cell RNA-seq, we inferred self-reinforcing and mutually exclusive regulatory networks controlling the different cell states and predicted transcription factors (TFs) shaping the chromatin landscape of Th17 cell pathogenicity. We validated one novel TF, BACH2, which promotes immunomodulatory npTh17 programs and restrains pro-inflammatory Th1-like programs in Th17 cells and showed genetic evidence for protective variants in the human BACH2 locus associated with multiple sclerosis. Our work uncovered mechanisms that regulate Th17 heterogeneity, revealed shared regulatory programs with other CD4+ T cell subsets, and identified novel drivers of Th17 pathogenicity as potential targets to mitigate autoimmunity.

immunology↗