GAN-WGCNA: Calculating gene modules to identify key intermediate regulators in cocaine addiction

PLoS One. 2024 Oct 3;19(10):e0311164. doi: 10.1371/journal.pone.0311164. eCollection 2024.

Abstract

Understanding time-series interplay of genes is essential for diagnosis and treatment of disease. Spatio-temporally enriched NGS data contain important underlying regulatory mechanisms of biological processes. Generative adversarial networks (GANs) have been used to augment biological data to describe hidden intermediate time-series gene expression profiles during specific biological processes. Developing a pipeline that uses augmented time-series gene expression profiles is needed to provide an unbiased systemic-level map of biological processes and test for the statistical significance of the generated dataset, leading to the discovery of hidden intermediate regulators. Two analytical methods, GAN-WGCNA (weighted gene co-expression network analysis) and rDEG (rescued differentially expressed gene), interpreted spatiotemporal information and screened intermediate genes during cocaine addiction. GAN-WGCNA enables correlation calculations between phenotype and gene expression profiles and visualizes time-series gene module interplay. We analyzed a transcriptome dataset of two weeks of cocaine self-administration in C57BL/6J mice. Utilizing GAN-WGCNA, two genes (Alcam and Celf4) were selected as missed intermediate significant genes that showed high correlation with addiction behavior. Their correlation with addictive behavior was observed to be notably significant in aspect of statistics, and their expression and co-regulation were comprehensively mapped in terms of time, brain region, and biological process.

MeSH terms

  • Animals
  • Cocaine / pharmacology
  • Cocaine-Related Disorders* / genetics
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Gene Regulatory Networks*
  • Male
  • Mice
  • Mice, Inbred C57BL*
  • Transcriptome

Substances

  • Cocaine

Grants and funding

This work was supported by the RandD programs of DGIST (22-CoE-BT-01), funded by the Ministry of Science and ICT of Korea. This research was supported by the KBRI Basic Research Program through the Korea Brain Research Institute, funded by the Ministry of Science and ICT (22-BR-02-04 [MC]) and the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2021R1A2C1003657 [TK,KL,MC] NRF-2023R1A2C1006248(WY)). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.