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Construction of Condition-Specific Gene Regulatory Network Using Kernel Canonical Correlation Analysis.

ABSTRACT: Gene expression profile or transcriptome can represent cellular states, thus understanding gene regulation mechanisms can help understand how cells respond to external stress. Interaction between transcription factor (TF) and target gene (TG) is one of the representative regulatory mechanisms in cells. In this paper, we present a novel computational method to construct condition-specific transcriptional networks from transcriptome data. Regulatory interaction between TFs and TGs is very complex, specifically multiple-to-multiple relations. Experimental data from TF Chromatin Immunoprecipitation sequencing is useful but produces one-to-multiple relations between TF and TGs. On the other hand, co-expression networks of genes can be useful for constructing condition transcriptional networks, but there are many false positive relations in co-expression networks. In this paper, we propose a novel method to construct a condition-specific and combinatorial transcriptional network, applying kernel canonical correlation analysis (kernel CCA) to identify multiple-to-multiple TF-TG relations in certain biological condition. Kernel CCA is a well-established statistical method for computing the correlation of a group of features vs. another group of features. We, therefore, employed kernel CCA to embed TFs and TGs into a new space where the correlation of TFs and TGs are reflected. To demonstrate the usefulness of our network construction method, we used the blood transcriptome data for the investigation on the response to high fat diet in a human and an arabidopsis data set for the investigation on the response to cold/heat stress. Our method detected not only important regulatory interactions reported in previous studies but also novel TF-TG relations where a module of TF is regulating a module of TGs upon specific stress.

SUBMITTER: Jeong D

PROVIDER: S-EPMC8172963 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Transcription factor (TF) has a significant influence on the state of a cell by regulating multiple down-stream genes. Thus, experimental and computational biologists have made great efforts to construct TF gene networks for regulatory interactions between TFs and their target genes. Now, an important research question is how to utilize TF networks to investigate the response of a plant to stress at the transcription control level using time-series transcriptome data. In this article, we present a new computational network, PropaNet, to investigate dynamics of TF networks from time-series transcriptome data using two state-of-the-art network analysis techniques, influence maximization and network propagation. PropaNet uses the influence maximization technique to produce a ranked list of TFs, in the order of TF that explains differentially expressed genes (DEGs) better at each time point. Then, a network propagation technique is used to select a group of TFs that explains DEGs best as a whole. For the analysis of Arabidopsis time series datasets from AtGenExpress, we used PlantRegMap as a template TF network and performed PropaNet analysis to investigate transcriptional dynamics of Arabidopsis under cold and heat stress. The time varying TF networks showed that Arabidopsis responded to cold and heat stress quite differently. For cold stress, bHLH and bZIP type TFs were the first responding TFs and the cold signal influenced histone variants, various genes involved in cell architecture, osmosis and restructuring of cells. However, the consequences of plants under heat stress were up-regulation of genes related to accelerating differentiation and starting re-differentiation. In terms of energy metabolism, plants under heat stress show elevated metabolic process and resulting in an exhausted status. We believe that PropaNet will be useful for the construction of condition-specific time-varying TF network for time-series data analysis in response to stress. PropaNet is available at http://biohealth.snu.ac.kr/software/PropaNet.

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Construction of Condition-Specific Gene Regulatory Network Using Kernel Canonical Correlation Analysis.

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