scholarly journals Network Analysis of Gene Transcriptions of Arabidopsis thaliana in Spaceflight Microgravity

Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 337
Author(s):  
Vidya Manian ◽  
Jairo Orozco ◽  
Harshini Gangapuram ◽  
Heeralal Janwa ◽  
Carlos Agrinsoni

The transcriptomic datasets of the plant model organism Arabidopsis thaliana grown in the International Space Station provided by GeneLab have been mined to isolate the impact of spaceflight microgravity on gene expressions related to root growth. A set of computational tools is used to identify the hub genes that respond differently in spaceflight with controlled lighting compared to on the ground. These computational tools based on graph-theoretic approaches are used to infer gene regulatory networks from the transcriptomic datasets. The three main algorithms used for network analyses are Least Absolute Shrinkage and Selection Operator (LASSO), Pearson correlation, and the Hyperlink-Induced Topic Search (HITS) algorithm. Graph-based spectral analyses reveal distinct properties of the spaceflight microgravity networks for the Wassilewskija (WS), Columbia (Col)-0, and mutant phytochromeD (phyD) ecotypes. The set of hub genes that are significantly altered in spaceflight microgravity are mainly involved in cell wall synthesis, protein transport, response to auxin, stress responses, and catabolic processes. Network analysis highlights five important root growth-regulating hub genes that have the highest outdegree distribution in spaceflight microgravity networks. These concerned genes coding for proteins are identified from the Gene Regulatory Networks (GRNs) corresponding to spaceflight total light environment. Furthermore, network analysis uncovers genes that encode nucleotide-diphospho-sugar interconversion enzymes that have higher transcriptional regulation in spaceflight microgravity and are involved in cell wall biosynthesis.

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Neel Patel ◽  
William S. Bush

Abstract Background Transcriptional regulation is complex, requiring multiple cis (local) and trans acting mechanisms working in concert to drive gene expression, with disruption of these processes linked to multiple diseases. Previous computational attempts to understand the influence of regulatory mechanisms on gene expression have used prediction models containing input features derived from cis regulatory factors. However, local chromatin looping and trans-acting mechanisms are known to also influence transcriptional regulation, and their inclusion may improve model accuracy and interpretation. In this study, we create a general model of transcription factor influence on gene expression by incorporating both cis and trans gene regulatory features. Results We describe a computational framework to model gene expression for GM12878 and K562 cell lines. This framework weights the impact of transcription factor-based regulatory data using multi-omics gene regulatory networks to account for both cis and trans acting mechanisms, and measures of the local chromatin context. These prediction models perform significantly better compared to models containing cis-regulatory features alone. Models that additionally integrate long distance chromatin interactions (or chromatin looping) between distal transcription factor binding regions and gene promoters also show improved accuracy. As a demonstration of their utility, effect estimates from these models were used to weight cis-regulatory rare variants for sequence kernel association test analyses of gene expression. Conclusions Our models generate refined effect estimates for the influence of individual transcription factors on gene expression, allowing characterization of their roles across the genome. This work also provides a framework for integrating multiple data types into a single model of transcriptional regulation.


2018 ◽  
Vol 15 (138) ◽  
pp. 20170809 ◽  
Author(s):  
Zhipeng Wang ◽  
Davit A. Potoyan ◽  
Peter G. Wolynes

Gene regulatory networks must relay information from extracellular signals to downstream genes in an efficient, timely and coherent manner. Many complex functional tasks such as the immune response require system-wide broadcasting of information not to one but to many genes carrying out distinct functions whose dynamical binding and unbinding characteristics are widely distributed. In such broadcasting networks, the intended target sites are also often dwarfed in number by the even more numerous non-functional binding sites. Taking the genetic regulatory network of NF κ B as an exemplary system we explore the impact of having numerous distributed sites on the stochastic dynamics of oscillatory broadcasting genetic networks pointing out how resonances in binding cycles control the network's specificity and performance. We also show that active kinetic regulation of binding and unbinding through molecular stripping of DNA bound transcription factors can lead to a higher coherence of gene-co-expression and synchronous clearance.


2009 ◽  
Vol 25 (15) ◽  
pp. 1898-1904 ◽  
Author(s):  
Chang H. Seo ◽  
Jeong-Rae Kim ◽  
Man-Sun Kim ◽  
Kwang-Hyun Cho

2021 ◽  
Author(s):  
Deborah Weighill ◽  
Marouen Ben Guebila ◽  
Kimberly Glass ◽  
John Quackenbush ◽  
John Platig

AbstractThe majority of disease-associated genetic variants are thought to have regulatory effects, including the disruption of transcription factor (TF) binding and the alteration of downstream gene expression. Identifying how a person’s genotype affects their individual gene regulatory network has the potential to provide important insights into disease etiology and to enable improved genotype-specific disease risk assessments and treatments. However, the impact of genetic variants is generally not considered when constructing gene regulatory networks. To address this unmet need, we developed EGRET (Estimating the Genetic Regulatory Effect on TFs), which infers a genotype-specific gene regulatory network (GRN) for each individual in a study population by using message passing to integrate genotype-informed TF motif predictions - derived from individual genotype data, the predicted effects of variants on TF binding and gene expression, and TF motif predictions - with TF protein-protein interactions and gene expression. Comparing EGRET networks for two blood-derived cell lines identified genotype-associated cell-line specific regulatory differences which were subsequently validated using allele-specific expression, chromatin accessibility QTLs, and differential TF binding from ChIP-seq. In addition, EGRET GRNs for three cell types across 119 individuals captured regulatory differences associated with disease in a cell-type-specific manner. Our analyses demonstrate that EGRET networks can capture the impact of genetic variants on complex phenotypes, supporting a novel fine-scale stratification of individuals based on their genetic background. EGRET is available through the Network Zoo R package (netZooR v0.9; netzoo.github.io).


2019 ◽  
Vol 19 (S1) ◽  
Author(s):  
Alexey V. Doroshkov ◽  
Dmitrii K. Konstantinov ◽  
Dmitrij A. Afonnikov ◽  
Konstantin V. Gunbin

2009 ◽  
Vol 3 (1) ◽  
Author(s):  
Chris J Needham ◽  
Iain W Manfield ◽  
Andrew J Bulpitt ◽  
Philip M Gilmartin ◽  
David R Westhead

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 319
Author(s):  
Ionut Sebastian Mihai ◽  
Debojyoti Das ◽  
Gabija Maršalkaite ◽  
Johan Henriksson

The reasons for selecting a gene for further study might vary from historical momentum to funding availability, thus leading to unequal attention distribution among all genes. However, certain biological features tend to be overlooked in evaluating a gene’s popularity. Here we present a meta-analysis of the reasons why different genes have been studied and to what extent, with a focus on the gene-specific biological features. From unbiased datasets we can define biological properties of genes that reasonably may affect their perceived importance. We make use of both linear and nonlinear computational approaches for estimating gene popularity to then compare their relative importance. We find that roughly 25% of the studies are the result of a historical positive feedback, which we may think of as social reinforcement. Of the remaining features, gene family membership is the most indicative followed by disease relevance and finally regulatory pathway association. Disease relevance has been an important driver until the 1990s, after which the focus shifted to exploring every single gene. We also present a resource that allows one to study the impact of reinforcement, which may guide our research toward genes that have not yet received proportional attention.


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