Cancer driver gene discovery in transcriptional regulatory networks using influence maximization approach

2019 ◽  
Vol 114 ◽  
pp. 103362 ◽  
Author(s):  
Majid Rahimi ◽  
Babak Teimourpour ◽  
Sayed-Amir Marashi
Author(s):  
Jorge Francisco Cutigi ◽  
Renato Feijo Evangelista ◽  
Rodrigo Henrique Ramos ◽  
Cynthia de Oliveira Lage Ferreira ◽  
Adriane Feijo Evangelista ◽  
...  

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Amin Emad ◽  
Saurabh Sinha

AbstractReconstruction of transcriptional regulatory networks (TRNs) is a powerful approach to unravel the gene expression programs involved in healthy and disease states of a cell. However, these networks are usually reconstructed independent of the phenotypic (or clinical) properties of the samples. Therefore, they may confound regulatory mechanisms that are specifically related to a phenotypic property with more general mechanisms underlying the full complement of the analyzed samples. In this study, we develop a method called InPheRNo to identify “phenotype-relevant” TRNs. This method is based on a probabilistic graphical model that models the simultaneous effects of multiple transcription factors (TFs) on their target genes and the statistical relationship between the target genes’ expression and the phenotype. Extensive comparison of InPheRNo with related approaches using primary tumor samples of 18 cancer types from The Cancer Genome Atlas reveals that InPheRNo can accurately reconstruct cancer type-relevant TRNs and identify cancer driver TFs. In addition, survival analysis reveals that the activity level of TFs with many target genes could distinguish patients with poor prognosis from those with better prognosis.


2018 ◽  
Vol 63 (9) ◽  
pp. 941-943 ◽  
Author(s):  
David Hsiehchen ◽  
Antony Hsieh

Author(s):  
Nawrah Khader ◽  
Virlana M Shchuka ◽  
Oksana Shynlova ◽  
Jennifer A Mitchell

Abstract The onset of labour is a culmination of a series of highly coordinated and preparatory physiological events that take place throughout the gestational period. In order to produce the associated contractions needed for fetal delivery, smooth muscle cells in the muscular layer of the uterus (i.e. myometrium) undergo a transition from quiescent to contractile phenotypes. Here, we present the current understanding of the roles transcription factors play in critical labour-associated gene expression changes as part of the molecular mechanistic basis for this transition. Consideration is given to both transcription factors that have been well-studied in a myometrial context, i.e. activator protein 1 (AP-1), progesterone receptors (PRs), estrogen receptors (ERs), and nuclear factor kappa B (NF-κB), as well as additional transcription factors whose gestational event-driving contributions have been demonstrated more recently. These transcription factors may form pregnancy- and labour- associated transcriptional regulatory networks in the myometrium to modulate the timing of labour onset. A more thorough understanding of the transcription factor-mediated, labour-promoting regulatory pathways holds promise for the development of new therapeutic treatments that can be used for the prevention of preterm labour in at-risk women.


2021 ◽  
Vol 22 (6) ◽  
pp. 2837
Author(s):  
Venura Herath ◽  
Jeanmarie Verchot

Potato virus X (PVX) belongs to genus Potexvirus. This study characterizes the cellular transcriptome responses to PVX infection in Russet potato at 2 and 3 days post infection (dpi). Among the 1242 differentially expressed genes (DEGs), 268 genes were upregulated, and 37 genes were downregulated at 2 dpi while 677 genes were upregulated, and 265 genes were downregulated at 3 dpi. DEGs related to signal transduction, stress response, and redox processes. Key stress related transcription factors were identified. Twenty-five pathogen resistance gene analogs linked to effector triggered immunity or pathogen-associated molecular pattern (PAMP)-triggered immunity were identified. Comparative analysis with Arabidopsis unfolded protein response (UPR) induced DEGs revealed genes associated with UPR and plasmodesmata transport that are likely needed to establish infection. In conclusion, this study provides an insight on major transcriptional regulatory networked involved in early response to PVX infection and establishment.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lei Chen ◽  
Shirley Luo ◽  
Abigail Dupre ◽  
Roshan P. Vasoya ◽  
Aditya Parthasarathy ◽  
...  

AbstractThe brush border is comprised of microvilli surface protrusions on the apical surface of epithelia. This specialized structure greatly increases absorptive surface area and plays crucial roles in human health. However, transcriptional regulatory networks controlling brush border genes are not fully understood. Here, we identify that hepatocyte nuclear factor 4 (HNF4) transcription factor is a conserved and important regulator of brush border gene program in multiple organs, such as intestine, kidney and yolk sac. Compromised brush border gene signatures and impaired transport were observed in these tissues upon HNF4 loss. By ChIP-seq, we find HNF4 binds and activates brush border genes in the intestine and kidney. H3K4me3 HiChIP-seq identifies that HNF4 loss results in impaired chromatin looping between enhancers and promoters at gene loci of brush border genes, and instead enhanced chromatin looping at gene loci of stress fiber genes in the intestine. This study provides comprehensive transcriptional regulatory mechanisms and a functional demonstration of a critical role for HNF4 in brush border gene regulation across multiple murine epithelial tissues.


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