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Original Research ARTICLE

Front. Genet. | doi: 10.3389/fgene.2021.652623

Construction of Condition-Specific Gene Regulatory Network using Kernel Canonical Correlation Analysis Provisionally accepted The final, formatted version of the article will be published soon. Notify me

 Dabin Jeong1,  Sangsoo Lim1,  Sangseon Lee1,  Minsik Oh1, Changyun Cho1, Hyeju Seong2,  Woosuk Jung2 and  Sun Kim1*
  • 1Seoul National University, South Korea
  • 2Konkuk University, South Korea

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 (ChIP-seq) 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 versus 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.

Keywords: kernel canonical correlation analysis, gene regulatory network, network dynamics, transcription factor, TF Cooperation, High-fat meal, Condition Specific Network

Received: 12 Jan 2021; Accepted: 26 Mar 2021.

Copyright: © 2021 Jeong, Lim, Lee, Oh, Cho, Seong, Jung and Kim. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Sun Kim, Seoul National University, Seoul, 151-742, South Korea, sunkim.submission@gmail.com