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Biology subjects

Riella, L. V.

Publications and source records attributed to Riella, L. V..

3 recordsLinked to original sources

a2iHelper: a Python toolkit for a differential editing site analysis of RNA-Seq data

BackgroundA-to-I RNA editing, mediated by ADAR enzymes, plays a crucial role in cancer and autoimmune disorders but lacks standardized tools for differential analysis. After reviewing 55 studies, it highlights significant methodological heterogeneity, hindering result comparability and reproducibility. To address this, we developed a2iHelper, a Python package that streamlines RNA editing analysis by filtering noise, performing statistical analyses, and generating visualizations. a2iHelper integrates seamlessly with Python machine learning tools, aiming to standardize and simplify RNA editing research. ResultsWe applied our methods to analyze A-to-I editing in a public dataset comparing wild-type and ADAR knockout. The source code is open, freely available on GitHub, and organized in a well-documented Python package. Using Snakemake for preprocessing, we conducted differential editing analysis on the top 104 most edited genes. The results include p-values from statistical tests, Odds ratios for Manhattan plots, and correlations between editing frequencies and gene expression, visualized in various plots. ConclusionsWe developed a2iHelper, a Python-based package for analyzing and visualizing A-to-I RNA editing data. It allows researchers with minimal programming experience to perform organized, reproducible editing analyses. Novice users can easily detect editing sites, filter noise, and generate figures, while advanced users can integrate functionalities into their workflows. a2iHelper runs on personal computers without needing High-Performance Computing resources.

bioinformatics↗

Innate extracellular Hsp70 inflammatory properties are mediated by the interaction of Siglec-E and LOX-1 receptors

Innate immune responses to cell damage-associated molecular patterns induce a controlled degree of inflammation, ideally avoiding the promotion of intense unwanted inflammatory adverse events. When released by damaged cells, Hsp70 can stimulate different responses that range from immune activation to immune suppression. The effects of Hsp70 are mediated through innate receptors expressed primarily by myeloid cells, such as dendritic cells (DCs). The regulatory innate receptors that bind to extracellular mouse Hsp70 (mHsp70) are not fully characterized, and neither are their potential interactions with activating innate receptors. Here, we describe that extracellular mHsp70 interacts with a receptor complex formed by inhibitory Siglec-E and activating LOX-1 on DCs. We also find that this interaction takes place within lipid microdomains, and Siglec-E acts as a negative regulator of LOX-1-mediated innate activation upon mHsp70 or oxidized LDL binding. Thus, HSP70 can both bind to and modulate the interaction of inhibitory and activating innate receptors on the cell surface. These findings add another dimension of regulatory mechanism to how self-molecules contribute to dampening of exacerbated inflammatory responses.

immunology↗

Immune Response of Transplanted Kidney Tissues Assembled from Organoid Building Blocks

The increasing scarcity of organs and the significant morbidity linked to dialysis requires the development of engineered kidney tissues from human-induced pluripotent stem cells. To accomplish this, integrative approaches that synergize scalable kidney organoid differentiation, tissue biomanufacturing, and comprehensive assessment of their immune response and host integration are essential. Here, we create engineered human kidney tissues composed of kidney organoid building blocks (OBBs) and transplant them into mice reconstituted with allogeneic human immune cells. We assess their host vascular integration, in vivo maturation, and their ability to trigger human immune responses. Tissue-infiltrating human immune cells are composed of effector T cells and innate cells. This immune infiltration leads to kidney tissue injury characterized by reduced microvasculature, enhanced kidney cell apoptosis, and a unique inflammatory gene signature comparable to kidney organ transplant rejection in humans. Upon treatment with the immunosuppressive agent Rapamycin, the induced immune response is greatly suppressed. Our model serves as a translational platform to study engineered kidney tissue immunogenicity and develop novel therapeutic targets for kidney rejection.

bioengineering↗