Browsing by Author "Kechavarzi, Bobak"

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    Dissecting the expression landscape of RNA-binding proteins in human cancers
    (2014-01) Kechavarzi, Bobak; Janga, Sarath Chandra
    Background RNA-binding proteins (RBPs) play important roles in cellular homeostasis by controlling gene expression at the post-transcriptional level. Results We explore the expression of more than 800 RBPs in sixteen healthy human tissues and their patterns of dysregulation in cancer genomes from The Cancer Genome Atlas project. We show that genes encoding RBPs are consistently and significantly highly expressed compared with other classes of genes, including those encoding regulatory components such as transcription factors, miRNAs and long non-coding RNAs. We also demonstrate that a set of RBPs, numbering approximately 30, are strongly upregulated (SUR) across at least two-thirds of the nine cancers profiled in this study. Analysis of the protein–protein interaction network properties for the SUR and non-SUR groups of RBPs suggests that path length distributions between SUR RBPs is significantly lower than those observed for non-SUR RBPs. We further find that the mean path lengths between SUR RBPs increases in proportion to their contribution to prognostic impact. We also note that RBPs exhibiting higher variability in the extent of dysregulation across breast cancer patients have a higher number of protein–protein interactions. We propose that fluctuating RBP levels might result in an increase in non-specific protein interactions, potentially leading to changes in the functional consequences of RBP binding. Finally, we show that the expression variation of a gene within a patient group is inversely correlated with prognostic impact. Conclusions Overall, our results provide a roadmap for understanding the impact of RBPs on cancer pathogenesis.
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    Uncovering RNA-Binding Proteins Implicated in Human Cancers by Integrating Genomics with Network-Based Approaches
    Kechavarzi, Bobak; Janga, Sarath
    RNA binding proteins (RBPs) are key regulatory mechanism in the cell. Their functions are varied depending on their localization, but many have been identified as essentially in translational regulation and cell proliferation. Their dysfunction has been linked to the development of various disease phenotypes and cancers. Using Human BodyMap v2.0 data and data made available through The Cancer Genome Atlas (TCGA), we proposed to observe the patterns of expression of RBPs in sixteen healthy tissues and across nine cancers, and their altering profiles. Additionally, by incorporating BioGrid protein-protein interaction data and CORUM protein complex information, we explore how network properties of the RNA may infer their dysfunction in cancers. The prognostic effect of RBPs classified by expression and network properties in breast cancer were determined using KM-Plotter. We observed that RBPs as a class are more highly expressed than other factors in the 16 human tissues, and furthermore that they are generally upexpressed in cancers. A smaller subset of RBPs (30) is many-fold higher expressed across a large portion of the observed cancers. Network metrics showed no significant differences, except for shortest path distances between subsets (Wilcox, p < 2x10·16). Similarly, complex size and membership did not show any trends or significant differences. The negative prognostic effect seems to be associated with mean path lengths of RBPs and their interaction with a highly dysregulated subset of RBPs.