Biology subjects

Reynaud, K.

Publications and source records attributed to Reynaud, K..

3 recordsLinked to original sources

bioRxiv2025

A translational transcriptomic signature of vaccine reactogenicity for the evaluation of novel formulations

Accurately predicting vaccine reactogenicity at the preclinical stage remains a major challenge in vaccine development, as conventional animal studies and in vitro assays capture general inflammation but fail to quantify local or systemic reactogenicity relevant to humans. Using transcriptomic data from the BioVacSafe consortium encompassing seven vaccines and immunostimulants in mice and five licensed vaccines in humans, we developed a cross-compartment and cross-species predictive model of vaccine reactogenicity. Reactogenicity classes were defined in mouse muscle based on the magnitude of transcriptomic responses and literature evidence. A penalized ordinal regression model was trained to predict both discrete classes and continuous scores of reactogenicity. Transcriptomic profiles from mouse muscle were highly predictive of reactogenicity, with key genes enriched in inflammatory and tissue repair pathways such as IL6/JAK/STAT3 signalling. The model retained strong performance when transferred to mouse blood and revealed shared transcriptional programs between compartments, suggesting coordinated innate responses. When applied to human blood, the classifier correctly ranked licensed vaccines by reactogenicity, identifying Fluad (MF59-adjuvanted) as the most reactogenic, in agreement with elevated C-reactive protein and ReactoScore values, while Engerix-B, Varilrix, and Stamaril were classified as low-reactogenicity formulations. These results align with clinical safety data and demonstrate that early transcriptomic signatures in mice can predict human reactogenicity profiles. Our study presents a pan-vaccine, cross-species transcriptomic signature that bridges preclinical and clinical data, offering a foundation for translational biomarkers and mechanism-informed assessment of vaccine tolerability.

bioinformatics↗

bioRxiv2024

Dbp1 is a low performance paralog of RNA helicase Ded1 that drives impaired translation and heat stress response

Ded1 and Dbp1 are paralogous conserved RNA helicases that enable translation initiation in yeast. Ded1 has been heavily studied but the role of Dbp1 is poorly understood. We find that the expression of these two helicases is controlled in an inverse and condition-specific manner. In meiosis and other long-term starvation states, Dbp1 expression is upregulated and Ded1 is downregulated, whereas in mitotic cells, Dbp1 expression is extremely low. Inserting the DBP1 ORF in place of the DED1 ORF cannot replace the function of Ded1 in supporting translation, partly due to inefficient mitotic translation of the DBP1 mRNA, dependent on features of its ORF sequence but independent of codon optimality. Global measurements of translation rates and 5 leader translation, activity of mRNA-tethered helicases, ribosome association, and low temperature growth assays show that--even at matched protein levels--Ded1 is more effective than Dbp1 at activating translation, especially for mRNAs with structured 5 leaders. Ded1 supports halting of translation and cell growth in response to heat stress, but Dbp1 lacks this function, as well. These functional differences in the ability to efficiently mediate translation activation and braking can be ascribed to the divergent, disordered N- and C-terminal regions of these two helicases. Altogether, our data show that Dbp1 is a "low performance" version of Ded1 that cells employ in place of Ded1 under long-term conditions of nutrient deficiency.

genomics↗

bioRxiv2021

Surveying the global landscape of post-transcriptional regulators

Numerous proteins regulate gene expression by modulating mRNA translation and decay. In order to uncover the full scope of these post-transcriptional regulators, we conducted an unbiased survey that quantifies regulatory activity across the budding yeast proteome and delineates the protein domains responsible for these effects. Our approach couples a tethered function assay with quantitative single-cell fluorescence measurements to analyze [~]50,000 protein fragments and determine their effects on a tethered mRNA. We characterize hundreds of strong regulators, which are enriched for canonical and unconventional mRNA-binding proteins. Regulatory activity typically maps outside the RNA-binding domains themselves, highlighting a modular architecture that separates mRNA targeting from post-transcriptional regulation. Activity often aligns with intrinsically disordered regions that can interact with other proteins, even in core mRNA translation and degradation factors. Our results thus reveal networks of interacting proteins that control mRNA fate and illuminate the molecular basis for post-transcriptional gene regulation.

molecular biology↗