Biology subjects

Francois, J.

Publications and source records attributed to Francois, J..

5 recordsLinked to original sources

bioRxiv2026

AdventML: Advanced Enzyme Temperature Prediction with Transformer-Based Embeddings and Resampling Strategies

Accurate prediction of enzymes optimal catalytic temperature (Topt) is crucial in biotechnology, as enzymes with extreme Topt values are highly desirable for reactions at extreme temperatures and for their general stability. However, experimental determination of Topt is costly, labor-intensive, and time-consuming. Meanwhile, existing computational methods suffer from small and imbalanced datasets, subop-timal predictions at extreme temperatures, and insufficient validation. In this study, we address these challenges by expanding the Topt dataset and validating on an independent test set based on sequence similarity. We further tackle these limitations by comparing multiple resampling techniques to improve predictions at extremes and by considering diverse protein rep-resentations and multiple machine learning architectures. Overall, the best performing models reached R2 {approx} 0.64 with MAE {approx} 7-8 {degrees}C, while extreme resampling improved tail performance (reducing tail MAE by up to ~1.8 {degrees}C). Notably, our models show improved performance over state-of-the-art prediction models. We also demonstrate that accurate prediction of Topt is achievable even in the absence of organ-ism growth temperature (OGT). Our Topt prediction models are made freely available as AdventML on GitHub.

bioinformatics↗

bioRxiv2025

Machine learning for optimal growth temperature prediction of prokaryotes using amino acid descriptors

MotivationThe optimal growth temperature (OGT) of organisms is valuable in bioprospecting enzymes that work under extreme conditions. Existing OGT prediction models achieve high accuracy, but mainly capture trends of overrepresented groups in the training set including organisms that thrive at moderate temperatures and those from well-described taxa. ResultsIn this study, we incorporated weighted scoring and phylogenetic splits to improve the generalizability of the prediction models. We first built a new growth temperature dataset comprising more than 21,000 species distributed over all three domains of life, with special attention to include OGT and extreme temperature data. We then trained machine learning models on the OGT data of 6,401 prokaryotes using proteome-averaged amino acid descriptors. The best-performing model was the multilayer perceptron with a cross-validated RMSE of 5.07{degrees}C ({+/-} 0.24) and an R2 of 0.89 ({+/-} 0.04). The most important proteome features were related to backbone flexibility, charged residues, as well as surface accessibility. Availability and ImplementationThe MLP model is integrated in the command line tool OGTFinder and available under MIT license at: https://github.com/SC-Git1/OGTFinder.

microbiology↗

bioRxiv2023

Fine-Tuning and Remodelling of Pectins Play a Key Role in the Maintenance of Cell Adhesion

Plant cell adhesion is essential for development and stress response, mediated by pectin-rich middle lamella deposition between cell walls. However, the precise control mechanism of cell adhesion remains unclear. The qua2-1 and esmd1-1 mutants provide a better understanding of this process and suggest a signaling pathway triggering the loss and restoration of adhesion via cell wall modifications. This study attempts to characterize the potential regulatory role of endogenous oligogalacturonides (OGs) and pectin modifications in the control of cell adhesion in Arabidopsis. From dark-grown hypocotyls, our extraction revealed seven distinct endogenous OGs with varying polymerization and modifications. Abundance variations of OGs were observed among wild type, qua2-1, esmd1-1, and qua2-1/esmd1-1 mutants. The structure of homogalacturonans was analyzed by enzymatic fingerprint, in order to identify changes in esterification patterns. Expression analysis of pectin-modifying enzymes showed significant variations in PME, PMEI, and PAE genes. Gene expressions correlate with homogalacturonans modifications and cell adhesion phenotypes. This study enhances our understanding of a feedback loop between the endogenous OGs, homogalacturonans esterification fine tuning, and pectin remodeling enzymes expression in controlling cell adhesion.

plant biology↗

bioRxiv2022

Genome-wide identification of fitness determinants in the Xanthomonas campestris bacterial pathogen during early stages of plant infection

Plant diseases are an important threat to food production. While major pathogenicity determinants required for disease have been extensively studied, less is known on how pathogens thrive during host colonization especially at early infection stages. Here, we used randomly barcoded-transposon insertion site sequencing (RB-TnSeq) to perform a genome-wide screen and identify key bacterial fitness determinants of the vascular pathogen Xanthomonas campestris pv. campestris (Xcc) during infection of the cauliflower host plant (Brassica oleracea). This high-throughput analysis was conducted in hydathodes, the natural entry site of Xcc, in xylem sap and in synthetic media. Xcc did not face a strong bottleneck during hydathode infection. 183 genes important for fitness were identified in plant-associated environments with functional enrichment in genes involved in metabolism when only few genes known to be involved in virulence were found to be affected. The biological relevance of 13 genes was independently confirmed by phenotyping single mutants. Notably, we show that the XC_3388, a protein with no known function (DUF1631), plays a key role in the adaptation and virulence of Xcc possibly through c-di-GMP-mediated regulation. This study thus revealed yet unsuspected social behaviors adopted by Xcc individuals when confined inside hydathodes at early infection stages.

microbiology↗

bioRxiv2020

A balance between matrix deformation and the coordination of turning events governs directed neutrophil migration in 3-D matrices

Three-dimensional (3-D) neutrophil migration is essential for immune surveillance and inflammatory responses. During 3-D migration, especially through extravascular spaces, neutrophils rely on frontal protrusions and rear contractions to squeeze and maneuver through extracellular matrices containing narrow pores. However, the role of matrix density and the cells ability to probe and remodel matrix pores during 3-D chemotaxis are far from being understood. We investigated these processes by tracking the trajectories of over 20,000 neutrophils in a 3-D migration device containing collagen matrices of varying concentrations and analyzing the shape of these trajectories at multiple scales. Additionally, we quantified the transient 3-D matrix deformations caused by the migrating cells. The mean pore size of our reconstituted collagen matrices decreased when the collagen concentration ([col]) was increased. In low-[col] matrices, neutrophils exerted large transient deformations and migrated in relatively straight trajectories. In contrast, they were not able to appreciably deform high- [col] matrices and adapted to this inability by turning more often to circumvent these narrow matrix pores. While this adaptation resulted in slower migration, the cells were able to balance the more frequent turning with the long-range directional bias necessary for chemotaxis. Based on our statistical analysis of cell trajectories, we postulate that neutrophils achieve this balance by using matrix obstacles as pivoting points to steer their motion towards the chemoattractant. Inhibiting myosin-II contractility or Arp2/3-mediated pseudopod protrusions not only compromised the cells ability to deform the matrix, but also made them switch to increased turning in more restrictive matrices when compared to untreated control cells. Both myosin-II contractility and Arp2/3-mediated branched polymerization of actin played a role in fast migration, but Arp2/3 was also crucial for neutrophils when coordinating the orientations of successive turns to prevent veering away from the chemotactic path. These results may contribute to an improved understanding of the mechanisms employed by migrating neutrophils in confined 3-D environments, as well as the molecular and environmental regulators for maintaining persistent motion.

biophysics↗