Biology subjects

Santoni, F.

Publications and source records attributed to Santoni, F..

5 recordsLinked to original sources

bioRxiv2026

COLSTATS: an interactive web platform for systematic colocalization of GWAS and QTL summary statistics

Colocalization of GWAS with QTL data is pivotal for identifying shared genetic determinants of molecular traits and diseases yet remains hindered by fragmented data sources and technical barriers. COLSTATS addresses this gap by offering a web-based Shiny platform that integrates 1,648,851 harmonized summary statistic datasets from key resources (GWAS Catalog, UK Biobank, GTEx, BluePrint, eQTLGen, and immune-phenotype studies), all formatted as VCFs aligned to hg38 with uniform chr_pos_ref_alt variant identifiers. Users can interactively select two traits, specify a genomic region or gene, define priors, and execute colocalization via coloc.abf, with results displayed in tabular and graphical form, downloadable as PDF, CSV, or PNG. The system includes result caching, history tracking, and an intuitive interface for streamlined exploration.COLSTATS is freely accessible at https://colstats.irgb.cnr.it. This resource empowers researchers, including non-bioinformaticians, to perform transparent and reproducible colocalization analyses efficiently.

bioinformatics↗

bioRxiv2025

Interdependent Dynamics of mRNA Expression and HIV-1 Viral Load: Insights from Transcriptomics and Mendelian Randomization

The interaction between HIV-1 and the host immune system plays a crucial role in the natural control and progression of the infection. Previous studies have identified APOBEC3G, Tetherin, SAMHD1, and SERINC5 as HIV-1 host restriction factors, which are counteracted by the viral proteins Vif, Vpu, and Nef, respectively. The blood expression levels of some of these host proteins are correlated with HIV load, suggesting that interindividual differences in the spontaneous control of HIV infection might lead to the identification of novel HIV restriction factors. Our study enrolled 150 participants from the Swiss HIV Cohort Study with human genome-wide genotyping data, pre-antiretroviral treatment peripheral blood mononuclear cells (PBMC) aliquots and HIV load measurements. Using BrB-seq, we quantified mRNA expression of all protein-coding genes and found significant associations between 792 genes and HIV load. Pathway analysis revealed that higher viral load associated with the upregulation of innate immune response, proteasome complex, mitochondrial and cell-cycle related activity, and with the downregulation of ribosomal transcripts and genes involved in cytokine-cytokine receptor interaction, including IL4R, IL7R, and TCF7. Mendelian Randomization confirmed the viral restriction activity of TRABD2A and identified new candidates as potential restriction factors. These findings provide novel insights into the host-virus interplay and suggest additional genes that may contribute to the natural control of HIV-1 infection.

immunology↗

bioRxiv2025

GenMasterTable: A user-friendly desktop application for filtering, summarising, and visualising large-scale annotated genetic variants

BackgroundThe rapid expansion of next-generation sequencing (NGS) technologies has generated vast amounts of genomic data, creating a growing demand for secure, scalable, and accessible tools to support variant interpretation. However, many existing solutions are command-line based, rely on cloud or server infrastructures that may pose data privacy risks, lack flexibility in supporting both VCF and CSV formats, or struggle to handle the scale and complexity of modern genomic datasets. There is a clear need for a user-friendly, locally operated application capable of efficiently processing annotated variant data for large-scale cohort level analysis. ResultsWe introduce GenMasterTable, a free, secure, and cross-platform desktop application designed to simplify variant analysis through an intuitive graphical user interface (GUI). As the first tool to enable comprehensive cohort-level analysis from both VCF and CSV files, GenMasterTable provides advanced functionality for merging, filtering, summarizing, and visualizing large-scale annotated datasets. Tailored for users without programming expertise, it enables rapid and accurate exploration of genetic variants, making it a practical solution for both research and clinical settings. ConclusionGenMasterTable addresses critical limitations in current variant analysis workflows by combining usability, data security, and scalability. Its support for multiple input formats and locally executed operations empowers clinicians, geneticists, and researchers to perform comprehensive variant analysis efficiently without the need for programming expertise.

bioinformatics↗

bioRxiv2023

Pseudospatial transcriptional gradient analysis of hypothalamic ependymal cells: towards a new tanycyte classification

The ependyma lining the third ventricle (3V) in the mediobasal hypothalamus is recognized as a critical player in controlling energy balance and glucose homeostasis. Its molecularly distinct cell types, including diverse tanycyte subpopulations and typical ependymal cells, confer a high functional heterogeneity. The study of gene expression profiles and dynamics of ependymal cells has the potential to uncover fundamental mechanisms and pathways involved in metabolic regulation. Here, we cataloged 5481 hypothalamic ependymocytes using FACS-assisted single-cell RNA sequencing from fed, 12h-fasted, and 24h-fasted adult male mice. First, standard clustering analysis revealed the limitation of the current characterization regarding the different ependymal cell subpopulations along the 3V. Indeed, while typical ependymal cells and {beta}2-tanycytes are sharply defined at the molecular level, other subpopulations (i.e., {beta}1-, 2-, and 1 tanycytes) display fuzzy boundaries and very few specific markers. Moreover, we observed that 12h- and 24h-fasting dynamically modulate gene expression, increasing tanycyte subgroup heterogeneity. Secondly, pseudospatial trajectory analysis based on peculiar UMAP neuroanatomical distribution improved the identification of tanycyte markers, distinguishing specific versus overlapping features and better segregating tanycyte specific versus standard functions. Intriguingly, we discovered numerous functions related to tanycyte-neuron and tanycyte-synapse interactions with modulation by energy balance. Finally, combining pseudospatial analysis and gene regulatory network inference, we observed that fasting dynamically shifts patterns in gene expression and transcription activity along the 3V, creating a metabolic and functional switch for some subpopulations. Altogether, this data provides a mechanism through which energy status leads to distinct cell type-specific responses along the 3V and gives new insights into molecular diversity underlying tanycyte classification.

neuroscience↗

bioRxiv2023

Transcriptomic profiling of murine GnRH neurons reveals developmental trajectories linked to human reproduction

Gonadotropin-releasing hormone (GnRH) neurons play a crucial role in human reproduction and are associated with a spectrum of conditions. However, the underlying biological mechanisms remain elusive due to their small number and sparse distribution. We performed transcriptomic profiling of GnRH neurons during mouse embryonic development, revealing their molecular identity and gene expression dynamics. Our findings show that GnRH neurons undergo a profound transcriptional shift as they migrate from the nose to the brain and that distinct expression trajectories are associated with critical biological processes, including cell migration, neuronal projections, and synapse formation. Cell-to-cell communication analysis revealed timely and spatially restricted modulation of signaling pathways involving known molecules, such as Semaphorins and Plexins, and novel candidates, such as Neurexins and Endothelins. Using GWAS genes linked to human reproductive onset, we found a specific association with GnRH neuron trajectories rising in late developmental stages and involved in neuron maturation and connectivity. Finally, analysis of the genetic burden in a large cohort of patients with congenital GnRH deficiency revealed specific GnRH neuron trajectories with a significant mutation load compared to controls. In conclusion, this study revealed the gene expression dynamics underlying GnRH neuron embryonic development and provides novel insights linking GnRH neuron biology to human reproduction.

developmental biology↗