Comparative Analysis of Normalization Methods for Network Propagation

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

H3K9 histone acetylation predicts pluripotency and reprogramming capacity of ES cells

The pluripotent genome is characterized by unique epigenetic features and a decondensed chromatin conformation. However, the relationship between epigenetic regulation and pluripotency is not altogether clear. Here, using an enhanced MEF/ESC fusion protocol, we compared the reprogramming potency and histone modifications of different embryonic stem cell (ESC) lines (R1, J1, E14, C57BL/6) and found that E14 ESCs are significantly less potent, with significantly reduced H3K9ac levels. Treatment of E14 ESCs with histone deacetylase (HDAC) inhibitors (HDACi) increased H3K9ac levels and restored their reprogramming capacity. Microarray and H3K9ac ChIP-seq analyses, suggested increased extracellular matrix (ECM) activity following HDACi treatment in E14 ESCs. These data suggest that H3K9ac may predict pluripotency and that increasing pluripotency by HDAC inhibition acts through H3K9ac to enhance the activity of target genes involved in ECM production to support pluripotency

Exploring multisite heterogeneity of human basal cell carcinoma proteome and transcriptome.

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