Biology subjects

Salignon, J.

Publications and source records attributed to Salignon, J..

3 recordsLinked to original sources

bioRxiv2025

Pasta, an age-shift transcriptomic clock, maps the chemical and genetic determinants of aging and rejuvenation

With the growing burden of age-related diseases, understanding and modulating the aging process has become a priority. Transcriptomic aging clocks (TACs) can track biological age but remain limited by platform dependence, tissue specificity, or restricted accessibility. To address this, we developed Pasta, a robust and broadly applicable human TAC built using a novel age-shift learning framework. Pasta accurately predicted relative age across diverse tissues, data types, including bulk and single-cell RNA-Seq as well as microarray data, and species. Its predictions aligned with senescent and stem-like cellular states, with model coefficients enriched for p53 and DNA damage response pathways. Pastas age scores correlated with tumor grade and patient survival in several cancer types, indicating potential clinical relevance. Applied to the Connectivity Map L1000 dataset, Pasta identified both established and previously unrecognized age-modulatory compounds and genetic perturbations, highlighting mitochondrial translation and mRNA splicing as key determinants of cellular propensity for aging and rejuvenation, respectively. Experimental validation confirmed pralatrexate as a potent senescence inducer and piperlongumine as a rejuvenating agent. Together, these findings establish Pasta as a versatile and accessible tool for aging research and therapeutic discovery.

bioinformatics↗

bioRxiv2023

Cactus: a user-friendly and reproducible ATAC-Seq and mRNA-Seq analysis pipeline for data preprocessing, differential analysis, and enrichment analysis

The ever decreasing cost of Next-Generation Sequencing coupled with the emergence of efficient and reproducible analysis pipelines has rendered genomic methods more accessible. However, downstream analyses are basic or missing in most workflows, creating a significant barrier for non-bioinformaticians. To help close this gap, we developed Cactus, an end-to-end pipeline for analyzing ATAC-Seq and mRNA-Seq data, either separately or jointly. Its Nextflow-, container-, and virtual environment-based architecture ensures efficient and reproducible analyses. Cactus preprocesses raw reads, conducts differential analyses between conditions, and performs enrichment analyses in various databases, including DNA-binding motifs, ChIP-Seq binding sites, chromatin states, and ontologies. We demonstrate the utility of Cactus in a multi-modal and multi-species case study as well as by showcasing its unique capabilities as compared to other ATAC-Seq pipelines. In conclusion, Cactus can assist researchers in gaining comprehensive insights from chromatin accessibility and gene expression data in a quick, user-friendly, and reproducible manner.

bioinformatics↗

bioRxiv2017

Genomics of cellular proliferation under periodic stress

Living systems control cell growth dynamically by processing information from their environment. Although responses to one environmental change have been intensively studied, little is known about how cells react to fluctuating conditions. Here we address this question at the genomic scale by measuring the relative proliferation rate (fitness) of 3,568 yeast gene deletion mutants in out-of-equilibrium conditions: periodic oscillations between two salinity conditions. Fitness and its genetic variance largely depended on the stress period. Surprisingly, dozens of mutants displayed pronounced hyperproliferation at short periods, identifying unexpected controllers of growth under fast dynamics. We validated the implication of the high-affinity cAMP phosphodiesterase and of a regulator of protein translocation to mitochondria in this control. The results illustrate how natural selection acts on mutations in a fluctuating environment, highlighting unsuspected genetic vulnerabilities to periodic stress in molecular processes that are conserved across all eukaryotes.

systems biology↗