Cost-effectiveness of CTC guided chemo- or endocrine therapy in ER+ HER2- metastatic breast cancer – results from a randomized controlled multicenter trial

Patients with metastatic, Estrogen Receptor (ER) positive, HER2-negative, breast cancer, before initiating CDK4/6 inhibitors, receive either single agent endocrine- or chemotherapy based on their clinical risk. In this first-ever trial-based economic evaluation of Circulating Tumor Cells (CTCs), the cost-effectiveness of standardizing the prescription of endocrine- or chemotherapy using a CTC count threshold (with >5 CTCs/7.5mL indicative of unfavorable disease outcomes) was compared to current clinical practice. N=755 ER+ HER2-patients, enrolled in 17 French centres, were randomized to CTC guided or standard of care and were treated according to either through the CTC score or clinical examination. Health state utilities were calculated by mapping the QLQ-C30 to EQ-5D utilities and used to calculate Quality-Adjusted Life Years (QALY) over a 2-year time horizon. Bootstrapping and additional sensitivity analyses were performed to quantify the impact of uncertainty. Health outcomes in both arms were similar, but costs were higher in the CTC guided arm (€19,403) compared to the usual care (€18,254), resulting in an ICER of €104,078/QALY in favor of usual care. However, when the analysis was performed for the clinically high- and low-risk groups separately, CTC enumeration could be a dominant strategy (cost saving) if treatment is de-escalated in clinically high-risk patients as indicated by CTC scores. However, the current analysis was based on the PFS and OS data reported in 2021 and long-term Overall Survival data is collected since then (JCO, 2023 in press). A further analysis of the health economic impact of CTC enumeration in clinically low and high-risk groups is therefore indicated

Wood Utilization Is Dependent on Catalase Activities in the Filamentous Fungus Podospora anserina

Catalases are enzymes that play critical roles in protecting cells against the toxic effects of hydrogen peroxide. They are implicated in various physiological and pathological conditions but some of their functions remain unclear. In order to decipher the role(s) of catalases during the life cycle of Podospora anserina, we analyzed the role of the four monofunctional catalases and one bifunctional catalase-peroxidase genes present in its genome. The five genes were deleted and the phenotypes of each single and all multiple mutants were investigated. Intriguingly, although the genes are differently expressed during the life cycle, catalase activity is dispensable during both vegetative growth and sexual reproduction in laboratory conditions. Catalases are also not essential for cellulose or fatty acid assimilation. In contrast, they are strictly required for efficient utilization of more complex biomass like wood shavings by allowing growth in the presence of lignin. The secreted CATB and cytosolic CAT2 are the major catalases implicated in peroxide resistance, while CAT2 is the major player during complex biomass assimilation. Our results suggest that P. anserina produces external H2O2 to assimilate complex biomass and that catalases are necessary to protect the cells during this process. In addition, the phenotypes of strains lacking only one catalase gene suggest that a decrease of catalase activity improves the capacity of the fungus to degrade complex biomass

BRANet: Graph-based Integration of Multi-omics Data with Biological a priori for Regulatory Network Inference

International audienc

BRANet: Graph-based Integration of Multi-omics Data with Biological a priori for Regulatory Network Inference

International audienc

Multiomics Data Integration for Gene Regulatory Network Inference with Exponential Family Embeddings

International audienceThe advent of omics technologies has enabled the generation of huge, complex, heterogeneous, and high-dimensional omics data. Imposing numerous challenges in data integration, these data could lead to a better understanding of the organism's cellular system. Omics data are typically represented as networks to study relations between biological entities, such as protein-protein interaction, gene regulation, and signal transduction. To this end, network embedding approaches allow us to learn latent feature representations for nodes of a graph structure. In this study, we propose a new methodology to learn embeddings by modeling the underlying interactions among biological entities (nodes) with exponential family distributions from a well-chosen set of omics modalities. We evaluate our proposed method based on the gene regulatory network (GRN) inference problem. As the ground truth for evaluation, we use GRN available in public databases and demonstrate its effectiveness by comparing to other network integration approaches

Multiomics Data Integration for Gene Regulatory Network Inference with Exponential Family Embeddings

International audienceThe advent of omics technologies has enabled the generation of huge, complex, heterogeneous, and high-dimensional omics data. Imposing numerous challenges in data integration, these data could lead to a better understanding of the organism's cellular system. Omics data are typically represented as networks to study relations between biological entities, such as protein-protein interaction, gene regulation, and signal transduction. To this end, network embedding approaches allow us to learn latent feature representations for nodes of a graph structure. In this study, we propose a new methodology to learn embeddings by modeling the underlying interactions among biological entities (nodes) with exponential family distributions from a well-chosen set of omics modalities. We evaluate our proposed method based on the gene regulatory network (GRN) inference problem. As the ground truth for evaluation, we use GRN available in public databases and demonstrate its effectiveness by comparing to other network integration approaches

The cellulase induction system in Trichoderma reesei strains remains well conserved despite several generations of random mutagenesis and screening

International audienceno abstrac

Sensitivity to hydrogen peroxide (H₂O₂) of wild type and the catalase mutant strains.

<p>Upper panel depicts the growth phenotypes. The strains were inoculated at 27°C on solid M2 medium without H₂O₂ (M2) or with 0.025% or 0.05% H₂O₂. Diameters (mm) of the thalli were measured after 48 hours. Lower panel: Corresponding histograms. The value for each strain is an average of 6 cultures and error bars represent standard deviation. Significant changes are indicated by an asterisk (p<0.001).</p