Biology subjects

Souza, D.

Publications and source records attributed to Souza, D..

3 recordsLinked to original sources

bioRxiv2024

Spatial Deconvolution of Cell Types and Cell States at Scale Utilizing TACIT

Identifying cell types and states remains a time-consuming and error-prone challenge for spatial biology. While deep learning is increasingly used, it is difficult to generalize due to variability at the level of cells, neighborhoods, and niches in health and disease. To address this, we developed TACIT, an unsupervised algorithm for cell annotation using predefined signatures that operates without training data, using unbiased thresholding to distinguish positive cells from background, focusing on relevant markers to identify ambiguous cells in multiomic assays. Using five datasets (5,000,000-cells; 51-cell types) from three niches (brain, intestine, gland), TACIT outperformed existing unsupervised methods in accuracy and scalability. Integration of TACIT-identified cell with a novel Shiny app revealed new phenotypes in two inflammatory gland diseases. Finally, using combined spatial transcriptomics and proteomics, we discover under- and overrepresented immune cell types and states in regions of interest, suggesting multimodality is essential for translating spatial biology to clinical applications.

bioinformatics↗

bioRxiv2023

Short-term consumption of ultra-processed semi-synthetic diets impairs the sense of smell and brain metabolism in mice

The prevalence of highly-palatable, ultra-processed food in our modern diet has exacerbated obesity rates and contributed to a global health crisis. While accumulating evidence suggests that chronic consumption of ultra-processed semi-synthetic food is detrimental to sensory and neural physiology, it is unclear whether its short-term intake has adverse effects. Here, we assessed how short-term consumption (<2 months) of three ultra-processed diets (one grain-based diet, and two semi-synthetic) influence olfaction and brain metabolism in mice. Our results demonstrate that short-term consumption of semi-synthetic diets, regardless of macronutrient composition, adversely affect odor-guided behaviors, physiological responses to odorants, transcriptional profiles in the olfactory mucosa and brain regions, and brain glucose metabolism and mitochondrial respiration. These findings reveal that even short periods of ultra-processed semi-synthetic food consumption are sufficient to cause early olfactory and brain abnormalities, which has the potential to alter food choices and influence the risk of developing metabolic disease.

neuroscience↗

bioRxiv2021

Characterisation of the Ubiquitin-ESCRT pathway in Asgard archaea sheds new light on origins of membrane trafficking in eukaryotes

The ESCRT machinery performs a critical role in membrane remodelling events in all eukaryotic cells, including in membrane trafficking, membrane repair, cytokinetic abscission, in viral egress, and in the generation of extracellular vesicles. While the machinery is complex in modern day eukaryotes, where it comprises dozens of proteins, the system has simpler and more ancient origins. Indeed, homologues of ESCRT-III and the Vps4 ATPase, the proteins that execute the final membrane scission reaction, play analogous roles in cytokinesis and potentially in extracellular vesicle formation in TACK archaea where ESCRT-I and II homologues seem to be absent. Here, we explore the phylogeny, structure, and biochemistry of homologues of the ESCRT machinery and the associated ubiquitylation system found in genome assemblies of the recently discovered Asgard archaea. In these closest living prokaryotic relatives of eukaryotes, we provide evidence for the ESCRT-I and II sub-complexes being involved in the ubiquitin-directed recruitment of ESCRT-III,_as it is in eukaryotes. This analysis suggests a pre-eukaryotic origin for the Ub-coupled ESCRT system and a likely path of ESCRT evolution via a series of gene duplication and diversification events.

cell biology↗