Biology subjects

Canete, P. F.

Publications and source records attributed to Canete, P. F..

2 recordsLinked to original sources

bioRxiv2024

Inferring gene regulatory networks by hypergraph variational autoencoder

In constructing Gene Regulatory Networks (GRNs), it is crucial to consider cellular heterogeneity and differential gene regulatory modules. However, traditional methods have predominantly focused on cellular heterogeneity, approaching the subject from a relatively narrow scope. We present HyperG-VAE, a Bayesian deep generative model that utilizes a hypergraph to model single-cell RNA sequencing (scRNA-seq) data. HyperG-VAE employs a cell encoder with a Structural Equation Model to address cellular heterogeneity and build GRNs, alongside a gene encoder using hypergraph self-attention to identify gene modules. Encoders are synergistically optimized by a decoder, enabling HyperG-VAE to excel in GRN inference, single-cell clustering, and data visualization, evidenced by benchmarks. Additionally, HyperG-VAE effectively reveals gene regulation patterns and shows robustness in varied downstream analyses, demonstrated using B cell development data in bone marrow. The interplay of encoders by the overlapping genes between predicted GRNs and gene modules is further validated by gene set enrichment analysis, underscoring that the gene encoder boosts the GRN inference. HyperG-VAE proves efficient in scRNA-seq data analysis and GRN inference.

bioinformatics↗

bioRxiv2020

PD-L1hi plasmablasts limit the T cell response during the acute phase of parasite infections

During infections with protozoan parasites or virus, T cell immunosuppression is generated simultaneously with a high B cell activation. Here, we show that in T. cruzi infection, all plasmablasts detected had higher surface expression of PD-L1, than other mononuclear cells. PD-L1hi plasmablasts were induced in vivo in an antigen-specific manner and required help from Bcl-6+CD4+T cells. PD-L1hi expression was not a characteristic of all antibody-secreting cells since plasma cells found during the chronic phase of infection express PD-L1 but at lower levels. PD-L1hi plasmablasts were also present in mice infected with Plasmodium or with lymphocytic choriomeningitis virus, but not in mice with autoimmune disorders or immunized with T cell-dependent antigens. PD-L1hi plasmablasts suppressed T cell response, via PD-L1, in vitro and in vivo. Thus, this study reveals that extrafollicular PD-L1hi plasmablasts, which precede the germinal center (CG) response, are a suppressive population in infections that may influence T cell response. Brief summaryPathogens develop different strategies to settle in the host. We identified a plasmablats population induced by pathogens in acute infections which suppress T cell response.

immunology↗