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Biology subjects

Brunel, A.

Publications and source records attributed to Brunel, A..

3 recordsLinked to original sources

From vehicles to wildlife: transferable deep learning for trajectory generation

Realistic simulation of animal movement is fundamental to conservation, habitat modeling, and ecological scenario evaluation. Traditional approaches struggle to capture multi-scale trajectory dynamics, while generative deep learning for complete trajectory simulation remains largely unexplored in ecology due to data scarcity. We show that a diffusion model pre-trained on millions of vehicle GPS trajectories can be fine-tuned on hundreds of seabird central-place foraging trips to simultaneously generate ecologically realistic trajectories for five species and six breeding colonies. The fine-tuned model consistently outperforms four state-of-the-art baselines (GAN, VAE, HMM, iSSF) across movement metrics spanning step dynamics, spatial distribution, and behavioral temporality, with comparable or shorter computation times. Domain transfer reaches full performance in 35 minutes versus 7 hours from scratch, and conditioning on species and colony enables generalization to unseen combinations from as few as 10 trajectories. These results establish cross-domain transfer learning as a new paradigm for data-efficient generative animal movement modeling.

bioinformatics↗

Repression of exosome secretion by mutated β-catenin contributes to immune escape in hepatocellular carcinoma

Immune checkpoint inhibitors have produced encouraging results in cancer patients. However, the majority of {beta}-catenin-mutated tumors have been described as lacking immune infiltrates and resistant to immunotherapy. The mechanisms by which oncogenic {beta}-catenin affects immune surveillance remain unclear. Herein, we highlighted the involvement of {beta}-catenin in the regulation of the exosomal pathway and, by extension, in immune/cancer cell communication in hepatocellular carcinoma (HCC). We showed that mutated {beta}-catenin represses expression of SDC4 and RAB27A, two main actors in exosome biogenesis, in both liver cancer cell lines and HCC patient samples. Using nanoparticle tracking analysis and live-cell imaging, we further demonstrated that activated {beta}-catenin represses exosome release. Then, we demonstrated in 3D spheroid models that activation of {beta}-catenin promotes a decrease in immune cell infiltration through a defect in exosome secretion. Taken together, our results provide the first evidence that oncogenic {beta}-catenin plays a key role in exosome biogenesis. Our study gives new insight into the impact of {beta}-catenin mutations on tumor microenvironment remodeling, which could lead to the development of new strategies to enhance immunotherapeutic response.

cancer biology↗

Translatome-based classification reveals a dual metabolic dependency of a new tumor subtype of pancreatic cancer.

Molecular profiling of Pancreatic Ductal Adenocarcinoma (PDA), based on transcriptomic analyses, identifies two main prognostic subtypes (basal-like and classical), but does not allow personalized first-line treatment. To date, tumors have not been profiled based on protein synthesis rates, yet the step of mRNA translation is highly deregulated in both PDA cancer cells and their microenvironment. Using a collection of twenty-seven pancreatic Patient-Derived Xenografts (PDX), we performed genome-wide analysis of translated mRNA (translatome). Unsupervised bioinformatics analysis revealed a new tumor subtype harboring a low protein synthesis rate, but associated with a robust translation of mRNAs encoding effectors of the integrated stress response (ISR), including the transcription factor ATF4. Functional characterization of the "ISR-activated" human cancer cells revealed a high resistance to drugs, low autophagic capacities, and importantly, metabolic impairments in the serine synthesis and transsulfuration pathways. Overall, our study highlights the strength of translatomic profiling on PDA, which here revealed an unforeseen drug-resistant cancer cell phenotype, whose auxotrophy to both serine and cysteine may be amenable to targeted therapy.

cancer biology↗