Sancho, D. | bioRxiv Science

bioRxiv2023

SpatialDDLS: An R package to deconvolute spatial transcriptomics data using neural networks

SummarySpatial transcriptomics has changed our way to study tissue structure and cellular organization. However, there are still limitations in its resolution, and most available plaXorms do not reach a single cell resolution. To address this issue, we introduce SpatialDDLS, a fast neural network-based algorithm for cell type deconvolution of spatial transcriptomics data. SpatialDDLS leverages single-cell RNA sequencing (scRNA-seq) data to simulate mixed transcriptional profiles with predefined cellular composition, which are subsequently used to train a fully-connected neural network to uncover cell type diversity within each spot. By comparing it with two state-of-the-art spatial deconvolution methods, we demonstrate that SpatialDDLS is an accurate and faster alternative to the available state-of-the art tools. Availability and implementationThe R package SpatialDDLS is available via CRAN-The Comprehensive R Archive Network: https://CRAN.R-project.org/package=SpatialDDLS. A detailed manual of the main functionalities implemented in the package can be found at https://diegommcc.github.io/SpatialDDLS. Contactfscabo@cnic.es Supplementary informationSupplementary data are available at Bioinformatics online.

bioinformatics↗

bioRxiv2022

Specific targeting of inflammatory osteoclastogenesis by the probiotic yeast S. boulardii CNCM I-745 reduces bone loss in osteoporosis

Bone destruction is a hallmark of chronic inflammation, and bone-resorbing osteoclasts arising under such a condition differ from steady-state ones. However, osteoclast diversity remains poorly explored. Here, we combined transcriptomic profiling, differentiation assays and in vivo analysis in mouse to decipher specific traits for inflammatory and steady state osteoclasts. We identified and validated the pattern-recognition receptors (PRR) TLR2, Dectin-1 and Mincle, all involved in yeast recognition as major regulators of inflammatory osteoclasts. We showed that administration of the yeast probiotic Saccharomyces boulardi CNCM I-745 (Sb) in vivo reduced bone loss in OVX but not sham mice by reducing inflammatory osteoclasts. This beneficial impact of Sb is mediated by the regulation of the inflammatory environment required for the generation of inflammatory osteoclasts. We also showed that Sb derivatives as well as agonists of TLR2, Dectin-1 and Mincle specifically inhibited directly the differentiation of inflammatory but not steady state osteoclasts in vitro. These findings demonstrate a preferential use of the PRR-associated costimulatory differentiation pathway by inflammatory osteoclasts, thus enabling their specific inhibition, which opens new therapeutic perspectives for inflammatory bone loss.

physiology↗