Search

The activity of miRNA varies across different cell populations and systems, as part of the mechanisms that distinguish cell types and roles in living organisms and in human health and disease. Typically, miRNA regulation drives changes in the composition and levels of protein-coding RNA and of lncRNA, with targets being down-regulated when miRNAs are active. The term "miRNA activity" is used to refer to this transcriptional effect of miRNAs. This study introduces miTEA-HiRes, a method designed to facilitate the evaluation of miRNA activity at high resolution. The method applies to single-cell transcriptomics, type-specific single-cell populations, and spatial transcriptomics data. By comparing different conditions, differential miRNA activity is inferred. For instance, miTEA-HiRes analysis of peripheral blood mononuclear cells comparing Multiple Sclerosis patients to control groups revealed differential activity of miR-20a-5p and others, consistent with the literature on miRNA underexpression in Multiple Sclerosis. We also show miR-519a-3p differential activity in specific cell populations. This study introduces miTEA-HiRes, a method designed to facilitate the evaluation of miRNA activity at high resolution. The method applies to single cell transcriptomics, type-specific single cell populations, and spatial transcriptomics data. [ABSTRACT FROM AUTHOR]

Basal cell carcinoma (BCC) is the most common type of skin cancer. Due to multiple, potential underlying molecular tumor aberrations, clinical treatment protocols are not well-defined. This study presents multisite molecular heterogeneity profiles of human BCC based on RNA and proteome profiling. Three areas from lesions excised from 9 patients were analyzed. The focus was gene expression profiles based on proteome and RNA measurements of intra-tumor heterogeneity from the same patient and inter-tumor heterogeneity in nodular, infiltrative, and superficial BCC tumor subtypes from different patients. We observed significant overlap in intra- and inter-tumor variability of proteome and RNA expression profiles, showing significant multisite heterogeneity of protein expression in the BCC tumors. Inter-subtype analysis has also identified unique proteins for each BCC subtype. This profiling leads to a deeper understanding of BCC molecular heterogeneity and potentially contributes to developing new sampling tools for personalized diagnostics therapeutic approaches to BCC. [ABSTRACT FROM AUTHOR]

Network propagation is a central tool in biological research. While a number of variants and normalizations have been proposed for this method, each has its own shortcomings and no large scale assessment of those variants is available. Here we propose a novel normalization method for network propagation that is based on evaluating the propagation results against those obtained on randomized networks that preserve node degrees. In this way, our method overcomes potential biases of previous methods. We evaluate its performance on multiple large scale datasets and find that it compares favorably to previous approaches in diverse gene prioritization tasks. We further demonstrate its utility on a focused dataset of telomere length maintenance in yeast. The normalization method is available at http://anat.cs.tau.ac.il/WebPropagate. [ABSTRACT FROM AUTHOR]

Network propagation is a powerful tool for genetic analysis which is widely used to identify genes and genetic modules that underlie a process of interest. Here we provide a graphical, web-based platform ( http://anat.cs.tau.ac.il/WebPropagate/ ) in which researchers can easily apply variants of this method to data sets of interest using up-to-date networks of protein–protein interactions in several organisms. [ABSTRACT FROM AUTHOR]