Biology subjects

Ben-Zvi, D.

Publications and source records attributed to Ben-Zvi, D..

5 recordsLinked to original sources

bioRxiv2026

Benchmarking single-cell foundation models reveals an advantage in the low-data regime for cell-type and disease-state prediction

Single-cell foundation models perform well on cell-type classification, but their value for disease-state prediction and their advantage over classical representations remains unclear. We benchmarked cell-representations from four foundation models using logistic regression, on 868 disease-prediction tasks (82 datasets) and 65 cell-type datasets from CELLxGENE. With full data, the baseline (log-normalized counts) outperformed the best model (TranscriptFormer-Sapiens) for cell type and matched it for disease. However, with few labeled cells, TranscriptFormer-Sapiens significantly outperformed the baseline in both tasks up to ~102 samples per class. Our comprehensive zero-shot benchmark identifies the data-scarce regime as a domain where Single-cell foundation models truly show advantage.

bioinformatics↗

bioRxiv2023

Inhibition of somatostatin enhances the long-term metabolic outcomes of sleeve gastrectomy in mice

Bariatric surgery is an effective obesity treatment, leading to weight loss and improvement in glycemia, that is characterized by hypersecretion of gastrointestinal hormones. However, weight regain and relapse of hyperglycemia are not uncommon. Here, we investigated the role of somatostatin (Sst) in bariatric surgery outcomes using a mouse model of sleeve gastrectomy (SG). Sst knockout (sst-ko) mice fed with a calorie-rich diet gained weight normally, and had a mild favorable metabolic phenotype compared to heterozygous sibling controls, including elevated plasma levels of Glp1. Mathematical modeling of the feedback inhibition between Sst and Glp1 showed that Sst exerts its maximal effect on Glp1 under conditions of high hormonal stimulation, such as following SG. Obese sst-ko mice that underwent SG had higher levels of Glp1 compared with heterozygous SG-operated controls. Accordingly, SG-sst-ko mice regained less weight than controls and maintained lower glycemia months after surgery. Obese wild-type mice that underwent SG and were treated daily with a Sst receptor inhibitor for two months, had higher Glp1 levels, regained less weight, and improved glycemia compared to saline- treated SG-operated controls. Our results suggest that Sst signaling inhibition enhances and maintains the long-term favorable metabolic outcomes of bariatric surgery.

physiology↗

bioRxiv2022

A multiomics comparison of weight loss interventions shows the distinct effects of bariatric surgery and intermittent fasting on hepatic metabolism

The prevalence of obesity and non-alcoholic fatty liver (NAFL) is steadily increasing. Weight loss can lead to improvement in NAFL in patients and in model organisms. Weight loss can be achieved through either dietary and lifestyle interventions, pharmacotherapy, and bariatric surgery. Some interventions, such as intermittent fasting, have been purported to have benefits beyond those conferred by weight loss alone. In this study, rats were provided a high-fat, high-sucrose diet for 7 weeks and then were assigned to strict caloric restriction with intermittent fasting (IF-CR) or to sleeve gastrectomy (SG) bariatric surgery, achieving equivalent weight loss. The two interventions were compared to ad-libitum fed controls. The metabolome of the blood entering the liver was analyzed in the three experimental groups, as well as the metabolome and transcriptome of the liver under fasting conditions, to test how different means of weight loss affect the input of the liver and hepatic metabolism. Surprisingly, the two interventions had different and often opposite effects on the composition of portal blood and liver metabolites. IF-CR resulted in sweeping changes across multiple central metabolic pathways, including an increase in de novo lipogenesis and triglyceride export, and upregulation of glycolysis, citric acid cycle, and the pentose phosphate pathway, as well as an increase in glycogen storage. Meanwhile, the effects of SG concentrated on one-carbon metabolic pathways, with changes in metabolite and transcript levels pointing to decreased transmethylation and methionine cycle activity, with downstream effects on levels of glutathione and the hepatic oxidative state. In conclusion, our study highlights how different means of weight loss affect distinct metabolic pathways and demonstrates a unique effect of bariatric surgery on hepatic one-carbon and redox pathways.

physiology↗

bioRxiv2021

Physically interacting beta-delta pairs in the regenerating pancreas revealed by single cell sequencing

The endocrine pancreas is able to regenerate in response to insult, including by driving beta-cells into the cell division cycle. Until recently, communication between neighboring cells in islets of Langerhans was overlooked by single-cell genomic technologies, which require rigorous tissue dissociation into single cells. Here, we utilize sorting of physically interacting cells (PICs) with single-cell RNA-sequencing to systematically map cellular interactions in the regenerating endocrine pancreas. The cellular landscape of the regenerated pancreas features regeneration-associated endocrine populations. We explore the unexpected heterogeneity of beta-cells in regeneration, including an interaction-specific program between paired beta and delta-cells. Our analysis suggests that the particular cluster of beta-cells that pair with delta-cells benefits from stress protection, implying that the interaction between beta and delta-cells safeguards against regeneration-associated challenges.

cell biology↗

bioRxiv2019

α-Synuclein-induced Kv4 channelopathy in mouse vagal motoneurons causes non-motor parkinsonian symptoms

No disease modifying therapy is currently available for Parkinsons disease (PD), the second most common neurodegenerative disease. The long non-motor prodromal phase of PD is a window of opportunity for early detection and intervention. However, we lack the pathophysiological understanding to develop selective biomarkers and interventions. By developing a mutant -synuclein selective-overexpression mouse model of prodromal PD, we identified a cell-autonomous selective Kv4 channelopathy in dorsal motor nucleus of the vagus (DMV) neurons. This functional remodeling of intact DMV neurons leads to impaired pacemaker function in vitro and in vivo, which in turn reduces gastrointestinal motility which is a common, very early symptom of prodromal PD. We show for the first time a causal chain of events from -synuclein via a biophysical dysfunction of specific neuronal populations to a clinically relevant prodromal symptom. These findings can facilitate the rational design of clinical biomarkers to identify people at risk for PD.

neuroscience↗