NECorr, a Tool to Rank Gene Importance in Biological Processes using Molecular Networks and Transcriptome Data

2018 ◽  
Author(s):  
Christophe Liseron-Monfils ◽  
Andrew Olson ◽  
Doreen Ware

AbstractThe challenge of increasing crop yield while decreasing plants’ susceptibility to various stresses can be lessened by understanding plant regulatory processes in a tissue-specific manner. Molecular network analysis techniques were developed to aid in understanding gene inter-regulation. However, few tools for molecular network mining are designed to extract the most relevant genes to act upon. In order to find and to rank these putative regulator genes, we generated NECorr, a computational pipeline based on multiple-criteria decision-making algorithms. With the objective of ranking genes and their interactions in a selected condition or tissue, NECorr uses the molecular network topology as well as global gene expression analysis to find hub genes and their condition-specific regulators. NECorr was applied to Arabidopsis thaliana flower tissue and identifies known regulators in the developmental processes of this tissue as well as new putative regulators. NECorr will accelerate translational research by ranking candidate genes within a molecular network of interest.

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yang Xi ◽  
Zhuang Jing ◽  
Wu Wei ◽  
Zhang Chun ◽  
Qi Quan ◽  
...  

Abstract Background Sodium butyrate (NaB) is produced through the fermentation of dietary fiber that is not absorbed and digested by the small intestine. Purpose Here, we aimed to investigate the effects of NaB on the proliferation, invasion, and metastasis of CRC cells and their potential underlying molecular mechanism(s). Methods The cell counting kit-8 (CCK-8) assay and EdU assay were used to detect cell proliferation ability, flow cytometry was used to investigate the induction of apoptosis and cell cycle progression, and the scratch-wound healing and transwell assays were used to evaluate cell migration and invasion, respectively. The human CRC genome information for tissues and CRC cells treated with NaB obtained from the NCBI GEO database was reannotated and used for differential RNA analysis. Functional and pathway enrichment analyses were performed for differentially expressed lncRNAs and mRNAs. A protein-protein interaction (PPI) network for the hub genes was constructed using the Cytoscape software. Targeted miRNAs were predicted based on the lnCeDB database, and a ceRNA network was constructed using the Cytoscape software. The Kaplan-Meier method was used to analyze patient prognosis using the clinical information and exon-seq data for CRC obtained from the Broad Institute’s GDAC Firehose platform. Results NaB decreased the proliferation ability of CRC cells in a dose- and time-dependent manner. The number of apoptotic CRC cells increased with the increase in NaB concentrations, and NaB induced a G1 phase block in CRC cells. Moreover, NaB suppressed the migratory and invasive capabilities of CRC cells. There were 666 differentially expressed mRNAs and 30 differentially expressed lncRNAs involved in the CRC inhibition by NaB. The PPI network and ceRNA network were constructed based on the differentially expressed mRNAs and lncRNAs. Three differentially expressed mRNAs, including HMGA2, LOXL2, and ST7, were significantly correlated with the prognosis of CRC. Conclusion NaB induces the apoptosis and inhibition of CRC cell proliferation, invasion, and metastasis by modulating complex molecular networks. RNA prediction and molecular network construction need to be the focus of further research in this direction.


2018 ◽  
Vol 115 (48) ◽  
pp. E11321-E11330 ◽  
Author(s):  
Jie Hou ◽  
Xiaowen Shi ◽  
Chen Chen ◽  
Md. Soliman Islam ◽  
Adam F. Johnson ◽  
...  

Changes in dosage of part of the genome (aneuploidy) have long been known to produce much more severe phenotypic consequences than changes in the number of whole genomes (ploidy). To examine the basis of these differences, global gene expression in mature leaf tissue for all five trisomies and in diploids, triploids, and tetraploids of Arabidopsis thaliana was studied. The trisomies displayed a greater spread of expression modulation than the ploidy series. In general, expression of genes on the varied chromosome ranged from compensation to dosage effect, whereas genes from the remainder of the genome ranged from no effect to reduced expression approaching the inverse level of chromosomal imbalance (2/3). Genome-wide DNA methylation was examined in each genotype and found to shift most prominently with trisomy 4 but otherwise exhibited little change, indicating that genetic imbalance is generally mechanistically unrelated to DNA methylation. Independent analysis of gene functional classes demonstrated that ribosomal, proteasomal, and gene body methylated genes were less modulated compared with all classes of genes, whereas transcription factors, signal transduction components, and organelle-targeted protein genes were more tightly inversely affected. Comparing transcription factors and their targets in the trisomies and in expression networks revealed considerable discordance, illustrating that altered regulatory stoichiometry is a major contributor to genetic imbalance. Reanalysis of published data on gene expression in disomic yeast and trisomic mouse cells detected similar stoichiometric effects across broad phylogenetic taxa, and indicated that these effects reflect normal gene regulatory processes.


2007 ◽  
Vol 75 (12) ◽  
pp. 5640-5650 ◽  
Author(s):  
Sean Y. Kassim ◽  
Sina A. Gharib ◽  
Brigham H. Mecham ◽  
Timothy P. Birkland ◽  
William C. Parks ◽  
...  

ABSTRACT Airway epithelium is the initial point of host-pathogen interaction in Pseudomonas aeruginosa infection, an important pathogen in cystic fibrosis and nosocomial pneumonia. We used global gene expression analysis to determine airway epithelial transcriptional responses dependent on matrilysin (matrix metalloproteinase 7 [MMP-7]) and stromelysin-2 (MMP-10), two MMPs induced by acute P. aeruginosa pulmonary infection. Extraction of differential gene expression (EDGE) analysis of gene expression changes in P. aeruginosa-infected organotypic tracheal epithelial cell cultures from wild-type, Mmp7 −/−, and Mmp10 −/− mice identified 2,091 matrilysin-dependent and 1,628 stromelysin-2-dependent genes that were differentially expressed. Key node network analysis showed that these MMPs controlled distinct gene expression programs involved in proliferation, cell death, immune responses, and signal transduction, among other host defense processes. Our results demonstrate discrete roles for these MMPs in regulating epithelial responses to Pseudomonas infection and show that a global genomics strategy can be used to assess MMP function.


Viruses ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 46 ◽  
Author(s):  
Yi-Sheng Sun ◽  
Zhang-Nv Yang ◽  
Fang Xu ◽  
Chen Chen ◽  
Hang-Jing Lu ◽  
...  

Enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) are the two most important pathogens of hand, foot, and mouth disease (HFMD). However, the neuropathogenesis of EV71 and CVA16 has not been elucidated. In our previous study, we established gerbils as a useful model for both EV71 and CVA16 infection. In this work, we used RNA-seq technology to analyze the global gene expression of the brainstem of EV71- and CVA16-infected gerbils. We found that 3434 genes were upregulated while 916 genes were downregulated in EV71-infected gerbils. In CVA16-infected gerbils, 1039 genes were upregulated, and 299 genes were downregulated. We also found significant dysregulation of cytokines, such as IP-10 and CXCL9, in the brainstem of gerbils. The expression levels of 10 of the most upregulated genes were confirmed by real-time RT-PCR, and the upregulated tendency of most genes was in accordance with the differential gene expression (DGE) results. Our work provided global gene expression analysis of virus-infected gerbils and laid a solid foundation for elucidating the neuropathogenesis mechanisms of EV71 and CVA16.


Metabolites ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 684
Author(s):  
Gaëlle Buche ◽  
Cyril Colas ◽  
Laëtitia Fougère ◽  
Emilie Destandau

Two species of oak are dominant in French forests: pedunculate oak (Quercus robur L.) and sessile oak (Quercus petraea Liebl.). Their differentiation is not straightforward but is essential to better understand their respective molecular content in order to better valorize them. Thus, to improve oak species identification, an untargeted UHPLC-HRMS/MS method associated with a two-step data treatment was developed to analyze a wide range of specialized metabolites enabling the comparison of both species of oak extracts. Pooled extracts from sessile and pedunculate oaks, composed of extracts from several trees of pure species from various origins, were compared using first the Venn diagram, as a quick way to get an initial idea of how close the extracts are, and then using a molecular network to visualize, on the one hand, the ions shared between the two species and, on the other hand, the compounds specific to one species. The molecular network showed that the two species shared common clusters mainly representative of tannins derivatives and that each species has specific molecules with similar fragmentation patterns, associated in specific clusters. This methodology was then applied to compare these two pooled extracts to unknown individuals in order to determine the species. The Venn diagram allowed for the quick presumption of the species of the individual and then the species could be assigned more precisely with the molecular network, at the level of specific clusters. This method, developed for the first time, has several interests. First, it makes it possible to discriminate the species and to correctly assign the species of unknown samples. Moreover, it gave an overview of the metabolite composition of each sample to better target oak tree utilization and valorization.


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