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Biology subjects

Sebag, M.

Publications and source records attributed to Sebag, M..

2 recordsLinked to original sources

In Silico Generation of Gene Expression profiles usingDiffusion Models

MotivationRNA-seq data is used for precision medicine (e.g., cancer predictions), which benefits from deep learning approaches to analyze complex gene expression data. However, transcriptomics datasets often have few samples compared to deep learning standards. Synthetic data generation is thus being explored to address this data scarcity. So far, only deep generative models such as Variational Autoencoders (VAEs) and Generative Adversarial Networks (GANs) have been used for this aim. Considering the recent success of diffusion models (DM) in image generation, we propose the first generation pipeline that leverages the power of said diffusion models. ResultsThis paper presents two state-of-the-art diffusion models (DDPM and DDIM) and achieves their adaptation in the transcriptomics field. DM-generated data of L1000 landmark genes show better predictive performance over TCGA and GTEx datasets. We also compare linear and nonlinear reconstruction methods to recover the complete transcriptome. Results show that such reconstruction methods can boost the performances of diffusion models, as well as VAEs and GANs. Overall, the extensive comparison of various generative models using data quality indicators shows that diffusion models perform best and second-best, making them promising synthetic transcriptomics generators. Availability and implementationData processing and full code available at: https://forge.ibisc.univevry.fr/alacan/rna-diffusion.git Contactalice.lacan@univ-evry.fr Supplementary informationSupplementary data are available at BioRxiv online.

bioinformatics↗

Single-cell transcriptional analysis of the immune tumour microenvironment during myeloma disease evolution

Multiple myeloma is universally preceded by a premalignant disease state. However, efforts to develop preventative therapeutic strategies are hindered by an incomplete understanding of the immune mechanisms associated with progression. Using single-cell RNA-sequencing, we profiled 104,880 cells derived from the bone marrow of V{kappa}*MYC mice across the myeloma progression spectrum, of which 97,720 were identified as non-malignant cells of the tumour microenvironment. Analysis of the non-malignant cells comprising the immune microenvironment identified mechanisms associated with disease progression in innate and adaptive immune cell populations. This included activation of IL-17 signaling in myeloid cells from precursor mice, accompanied by upregulation of Il6 gene expression in basophils. In the T/Natural killer cell compartment, we identified Tox-expressing CD8+ T cells enriched in the tumour microenvironment of mice with overt disease, with co-expression of LAG3 and PD-1, as well as elevated T cell exhaustion signatures in mice with early disease. We subsequently showed that early intervention with combinatorial blockade of LAG3 and PD-1 using neutralizing monoclonal antibodies delayed tumor progression and improved survival of V{kappa}*MYC mice. Together, this work provides insight into the biology of myeloma evolution and nominates a treatment strategy for early disease.

cancer biology↗