A5029001947- Bioinformatics and Genomic Networks
- Single-cell and spatial transcriptomics
- Genomics and Rare Diseases
- Gene expression and cancer classification
- Cancer Genomics and Diagnostics
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Gene Regulatory Network Analysis
- Pharmaceutical Economics and Policy
- Adipokines, Inflammation, and Metabolic Diseases
- RNA modifications and cancer
- Neuroinflammation and Neurodegeneration Mechanisms
- Epigenetics and DNA Methylation
- Heat shock proteins research
- Adipose Tissue and Metabolism
- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- Computational Drug Discovery Methods
- Endoplasmic Reticulum Stress and Disease
- Respiratory Support and Mechanisms
- Genetic Associations and Epidemiology
- Cardiovascular Disease and Adiposity
- Ubiquitin and proteasome pathways
- Chronic Lymphocytic Leukemia Research
- COVID-19 Clinical Research Studies
Ben-Gurion University of the Negev
2016-2025
Single-cell analysis of CD4 T cells reveals a population structure associated with inflammation and declined immunity in aging.
Human adipose depots are functionally distinct. Yet, recent single-nucleus RNA sequencing (snRNA-seq) analyses largely uncovered overlapping or similar cell-type landscapes. We hypothesized that adipocyte subtypes, differentiation trajectories and/or intercellular communication patterns could illuminate this depot similarity–difference gap. For this, we performed snRNA-seq of human subcutaneous visceral tissues (five ten samples, respectively). Of 27,665 nuclei in both depots, most were...
Abstract The sensitivity of the protein-folding environment to chaperone disruption can be highly tissue-specific. Yet, organization system across physiological human tissues has received little attention. Through computational analyses large-scale tissue transcriptomes, we unveil that is composed core elements are uniformly expressed tissues, and variable differentially fit with tissue-specific requirements. We demonstrate via a proteomic analysis muscle-specific signature functional...
Knowledge of the molecular interactions human proteins within tissues is important for identifying their tissue-specific roles and shedding light on tissue phenotypes. However, many protein-protein (PPIs) have no tissue-contexts. The TissueNet database bridges this gap by associating experimentally-identified PPIs with that were shown to express both pair-mates. Users can select a protein tissue, obtain network view query its tissue-associated PPIs. v.2 an updated version previously featured...
Differential network analysis, designed to highlight changes between conditions, is an important paradigm in biology. However, differential analysis methods have been typically compare two conditions and were rarely applied multiple protein interaction networks (interactomes). Importantly, large-scale benchmarks for their evaluation lacking.Here, we present a framework assessing the ability of human tissue interactomes tissue-selective processes disorders. For this, created benchmark 6499...
A longstanding puzzle in human genetics is what limits the clinical manifestation of hundreds hereditary diseases to certain tissues, while their causal genes are expressed throughout body. general conception that tissue-selective disease phenotypes emerge when masking factors operate unaffected but specifically absent or insufficient disease-manifesting tissues. Although this has critical impact on understanding manifestation, it was never challenged a systematic manner across variety and...
Abstract The role of different cell types and their interactions in Alzheimer’s disease (AD) is an open question. Here we pursued it by assembling a high-resolution cellular map the aging frontal cortex single nucleus RNA-seq 24 individuals with clinicopathologic characteristics. We used to infer neocortical architecture 638 profiled bulk RNA-seq, providing sample size necessary for identifying statistically robust associations. uncovered diverse populations associated AD, including...
How do aberrations in widely expressed genes lead to tissue-selective hereditary diseases? Previous attempts answer this question were limited testing a few candidate mechanisms. To at larger scale, we developed "Tissue Risk Assessment of Causality by Expression" (TRACE), machine learning approach predict that underlie diseases and selectivity-related features. TRACE utilized 4,744 biologically interpretable tissue-specific gene features inferred from heterogeneous omics datasets....
Mendelian diseases tend to manifest clinically in certain tissues, yet their affected cell types typically remain elusive. Single-cell expression studies showed that overexpression of disease-associated genes may point the types. Here, we developed a method infers disease-affected from preferential (PrEDiCT). We applied PrEDiCT single-cell data six human infer diseases. Overall, inferred likely for 328 corroborated our findings by literature text-mining, expert validation, and recapitulation...
Abstract Motivation The distinct functionalities of human tissues and cell types underlie complex phenotype–genotype relationships, yet often remain elusive. Harnessing the multitude bulk single-cell transcriptomes while focusing on processes can help reveal these functionalities. Results Tissue-Process Activity (TiPA) method aims to identify that are preferentially active or under-expressed in specific contexts, by comparing expression levels process genes between contexts. We tested TiPA...
Hereditary diseases and complex traits often manifest in specific tissues, whereas their causal genes are expressed many tissues that remain unaffected. Among the mechanisms have been suggested for this enigmatic phenomenon is dosage-sensitive compensation by paralogs of genes. Accordingly, tissue-selectivity stems from dosage imbalance between occurs particularly disease-susceptible tissues. Here, we used a large-scale dataset thousands tissue transcriptomes applied linear mixed model (LMM)...
ABSTRACT Motivation Differential network analysis, designed to highlight interaction changes between conditions, is an important paradigm in biology. However, analysis methods have been typically compare few were rarely applied protein networks (interactomes). Moreover, large-scale benchmarks for their evaluation lacking. Results Here, we assess five by applying them 34 human tissues interactomes. For this, created a manually-curated benchmark of 6,499 tissue-specific, gene ontology...
Abstract Background High and increasing drug prices have prompted the establishment of a broad range cost-containment treatment policies in health systems globally. In 2012, supplemental insurance program large Israeli maintenance organization (Clalit Health Services) introduced prior authorization process for second-line use ranibizumab patients with retinal disease whom bevacizumab proved to be ineffective. A Clalit steering committee established criteria based on cost periodically updated...
ABSTRACT Genetic studies of Mendelian and rare diseases face the critical challenges identifying pathogenic gene variants their modes-of-action. Previous efforts rarely utilized tissue-selective manifestation these for elucidation. Here we introduce an interpretable machine learning (ML) platform that utilizes heterogeneous large-scale tissue-aware datasets human genes, rigorously, concurrently quantitatively assesses hundreds candidate mechanisms per disease. The resulting ML is applicable...
ABSTRACT Human adipose depots are functionally distinct. Yet, recent single-nucleus RNA-sequencing (snRNA-seq) analyses largely uncovered overlapping/similar cell-type landscapes. We hypothesized that adipocytes subtypes, differentiation trajectories, and/or intercellular communication patterns could illuminate this depot similarity-difference gap. For this, we performed snRNA-seq of human subcutaneous and visceral tissue. Whereas the majority in both were ‘classical’, namely enriched lipid...
ABSTRACT A longstanding puzzle in human genetics is what limits the clinical manifestation of hundreds hereditary diseases to certain tissues or cell types, while their causal genes are present and expressed throughout body. Here we considered a possible role for paralogs affecting this tissue selectivity. It has been shown across organisms that can compensate loss each other. We hypothesized specifically disease imbalanced, leading insufficient compensation emergence phenotypes. While...
Abstract Background: Rising drug prices prompt the establishment of cost-containment treatment policies. Ranibizumab was approved for retinal diseases, although less-costly, off label, bevacizumab has been found equally effective. We describe a novel prior-authorization approach, which we applied to ranibizumab as second-line treatment, in non-responders first-line bevacizumab: A steering committee set funding criteria based on cost and updating clinical considerations; an ophthalmic...
Abstract The sensitivity of the protein-folding environment to chaperone disruption can be highly tissue-specific. Yet, organization system across physiological human tissues has received little attention. Here, we used tissue RNA-sequencing profiles analyze expression and chaperones 29 main tissues. We found that relative protein-coding genes, were significantly more ubiquitously expressed all Nevertheless, differential analysis revealed most up- or down-regulated in certain tissues,...
ABSTRACT Hereditary diseases manifest clinically in certain tissues, however their affected cell types typically remain elusive. Single-cell expression studies showed that overexpression of disease-associated genes may point to the types. Here, we developed a method infers disease-affected from preferential (PrEDiCT). We applied PrEDiCT single-cell data six human infer 1,113 hereditary diseases. Overall, identified 110 by 714 corroborated our findings literature text-mining and...