Dataset Information

SEGN: Inferring real-time gene networks mediating phenotypic plasticity.

ABSTRACT: The capacity of an organism to alter its phenotype in response to environmental perturbations changes over developmental time and is a process determined by multiple genes that are co-expressed in intricate but organized networks. Characterizing the spatiotemporal change of such gene networks can offer insight into the genomic signatures underlying organismic adaptation, but it represents a major methodological challenge. Here, we integrate the holistic view of systems biology and the interactive notion of evolutionary game theory to reconstruct so-called systems evolutionary game networks (SEGN) that can autonomously detect, track, and visualize environment-induced gene networks along the time axis. The SEGN overcomes the limitations of traditional approaches by inferring context-specific networks, encapsulating bidirectional, signed, and weighted gene-gene interactions into fully informative networks, and monitoring the process of how networks topologically alter across environmental and developmental cues. Based on the design principle of SEGN, we perform a transcriptional plasticity study by culturing Euphrates poplar, a tree that can grow in the saline desert, in saline-free and saline-stress conditions. SEGN characterize previously unknown gene co-regulation that modulates the time trajectories of the trees' response to salt stress. As a marriage of multiple disciplines, SEGN shows its potential to interpret gene interdependence, predict how transcriptional co-regulation responds to various regimes, and provides a hint for exploring the mass, energetic, or signal basis that drives various types of gene interactions.

SUBMITTER: Jiang L

PROVIDER: S-EPMC7516210 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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SEGN: Inferring real-time gene networks mediating phenotypic plasticity.

Jiang Libo L Griffin Christopher H CH Wu Rongling R

Computational and structural biotechnology journal 20200905

The capacity of an organism to alter its phenotype in response to environmental perturbations changes over developmental time and is a process determined by multiple genes that are co-expressed in intricate but organized networks. Characterizing the spatiotemporal change of such gene networks can offer insight into the genomic signatures underlying organismic adaptation, but it represents a major methodological challenge. Here, we integrate the holistic view of systems biology and the interactiv ...[more]

PMID: 33005313

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Project description:MotivationSingle cell transcriptional profiling opens up a new avenue in studying the functional role of cell-to-cell variability in physiological processes. The analysis of single cell expression profiles creates new challenges due to the distributive nature of the data and the stochastic dynamics of gene transcription process. The reconstruction of gene regulatory networks (GRNs) using single cell transcriptional profiles is particularly challenging, especially when directed gene-gene relationships are desired.ResultsWe developed SINCERITIES (SINgle CEll Regularized Inference using TIme-stamped Expression profileS) for the inference of GRNs from single cell transcriptional profiles. We focused on time-stamped cross-sectional expression data, commonly generated from transcriptional profiling of single cells collected at multiple time points after cell stimulation. SINCERITIES recovers directed regulatory relationships among genes by employing regularized linear regression (ridge regression), using temporal changes in the distributions of gene expressions. Meanwhile, the modes of the gene regulations (activation and repression) come from partial correlation analyses between pairs of genes. We demonstrated the efficacy of SINCERITIES in inferring GRNs using in silico time-stamped single cell expression data and single cell transcriptional profiles of THP-1 monocytic human leukemia cells. The case studies showed that SINCERITIES could provide accurate GRN predictions, significantly better than other GRN inference algorithms such as TSNI, GENIE3 and JUMP3. Moreover, SINCERITIES has a low computational complexity and is amenable to problems of extremely large dimensionality. Finally, an application of SINCERITIES to single cell expression data of T2EC chicken erythrocytes pointed to BATF as a candidate novel regulator of erythroid development.Availability and implementationMATLAB and R version of SINCERITIES are freely available from the following websites: http://www.cabsel.ethz.ch/tools/sincerities.html and https://github.com/CABSEL/SINCERITIES. The single cell THP-1 and T2EC transcriptional profiles are available from the original publications (Kouno et al., 2013; Richard et al., 2016). The in silico single cell data are available on SINCERITIES websites.Supplementary informationSupplementary data are available at Bioinformatics online.

Project description:BackgroundNovel strategies are required in order to handle the huge amount of data produced by microarray technologies. To infer gene regulatory networks, the first step is to find direct regulatory relationships between genes building the so-called gene co-expression networks. They are typically generated using correlation statistics as pairwise similarity measures. Correlation-based methods are very useful in order to determine whether two genes have a strong global similarity but do not detect local similarities.ResultsWe propose model trees as a method to identify gene interaction networks. While correlation-based methods analyze each pair of genes, in our approach we generate a single regression tree for each gene from the remaining genes. Finally, a graph from all the relationships among output and input genes is built taking into account whether the pair of genes is statistically significant. For this reason we apply a statistical procedure to control the false discovery rate. The performance of our approach, named REGNET, is experimentally tested on two well-known data sets: Saccharomyces Cerevisiae and E.coli data set. First, the biological coherence of the results are tested. Second the E.coli transcriptional network (in the Regulon database) is used as control to compare the results to that of a correlation-based method. This experiment shows that REGNET performs more accurately at detecting true gene associations than the Pearson and Spearman zeroth and first-order correlation-based methods.ConclusionsREGNET generates gene association networks from gene expression data, and differs from correlation-based methods in that the relationship between one gene and others is calculated simultaneously. Model trees are very useful techniques to estimate the numerical values for the target genes by linear regression functions. They are very often more precise than linear regression models because they can add just different linear regressions to separate areas of the search space favoring to infer localized similarities over a more global similarity. Furthermore, experimental results show the good performance of REGNET.

Dataset Information

SEGN: Inferring real-time gene networks mediating phenotypic plasticity.

Publications

SEGN: Inferring real-time gene networks mediating phenotypic plasticity.

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