Single-Cell Co-expression Analysis Reveals Distinct Functional Modules, Co-regulation Mechanisms and Clinical Outcomes

Jie Wang, Shuli Xia, Brian Arand, Heng Zhu, Raghu Machiraju, Kun Huang, Hong Kai Ji, Jiang Qian

Research output: Contribution to journalArticle


Co-expression analysis has been employed to predict gene function, identify functional modules, and determine tumor subtypes. Previous co-expression analysis was mainly conducted at bulk tissue level. It is unclear whether co-expression analysis at the single-cell level will provide novel insights into transcriptional regulation. Here we developed a computational approach to compare glioblastoma expression profiles at the single-cell level with those obtained from bulk tumors. We found that the co-expressed genes observed in single cells and bulk tumors have little overlap and show distinct characteristics. The co-expressed genes identified in bulk tumors tend to have similar biological functions, and are enriched for intrachromosomal interactions with synchronized promoter activity. In contrast, single-cell co-expressed genes are enriched for known protein-protein interactions, and are regulated through interchromosomal interactions. Moreover, gene members of some protein complexes are co-expressed only at the bulk level, while those of other complexes are co-expressed at both single-cell and bulk levels. Finally, we identified a set of co-expressed genes that can predict the survival of glioblastoma patients. Our study highlights that comparative analyses of single-cell and bulk gene expression profiles enable us to identify functional modules that are regulated at different levels and hold great translational potential.

Original languageEnglish (US)
Article numbere1004892
JournalPLoS Computational Biology
Issue number4
Publication statusPublished - Apr 1 2016


ASJC Scopus subject areas

  • Computational Theory and Mathematics
  • Modeling and Simulation
  • Ecology, Evolution, Behavior and Systematics
  • Genetics
  • Molecular Biology
  • Ecology
  • Cellular and Molecular Neuroscience

Cite this

Single-Cell Co-expression Analysis Reveals Distinct Functional Modules, Co-regulation Mechanisms and Clinical Outcomes. / Wang, Jie; Xia, Shuli; Arand, Brian; Zhu, Heng; Machiraju, Raghu; Huang, Kun; Ji, Hong Kai; Qian, Jiang.

In: PLoS Computational Biology, Vol. 12, No. 4, e1004892, 01.04.2016.

Research output: Contribution to journalArticle