Bombaci, M. | Search bioRxiv

bioRxiv2022

Combinatorial selection of biomarkers to optimize gene signatures in diagnostics and single cell applications

Here we present the combiroc R package, for signatures refinement in high throughput omics. Based on a ROC-driven marker selection, it can be used to find powerful smaller sub-signatures from scRNAseq experiments and to annotate cells using fewer markers. Trained on PBMC dataset, combiroc found NK marker combinations with high cell-discriminating power, in agreement with human protein atlas and that were validated both computationally and experimentally on independent datasets.

bioinformatics↗

bioRxiv2020

Insights into kinetics, release, and behavioral effects of brain-targeted hybrid nanoparticles forcholesterol delivery in Huntington disease

Supplementing brain cholesterol is emerging as a potential treatment for Huntingtons disease (HD), a genetic neurodegenerative disorder characterized, among other abnormalities, by inefficient brain cholesterol biosynthesis. However, delivering cholesterol to the brain is challenging due to the bloodbrain barrier (BBB), which prevents it from reaching the striatum, especially, with therapeutically relevant doses. Here we describe the distribution, kinetics, release, and safety of novel hybrid polymeric nanoparticles made of PLGA and cholesterol which were modified with an heptapeptide (g7) for BBB transit (hybrid-g7-NPs-chol). We show that these NPs rapidly reach the brain and target neural cells. Moreover, deuterium-labeled cholesterol from hybrid-g7-NPs-chol is released in a controlled manner within the brain and accumulates over time, while being rapidly removed from peripheral tissues and plasma. We confirm that systemic and repeated injections of the new hybrid-g7-NPs-chol enhanced endogenous cholesterol biosynthesis, prevented cognitive decline, and ameliorated motor defects in HD animals, without any inflammatory reaction. In summary, this study provides insights about the benefits and safety of cholesterol delivery through advanced brain-permeable nanoparticles for HD treatment.

neuroscience↗