TY - JOUR T1 - Identification of the Proliferation/Differentiation Switch in the Cellular Network of Multicellular Organisms A1 - Xia, Kai A1 - Xue, Huiling A1 - Dong, Dong A1 - Zhu, Shanshan A1 - Wang, Jiamu A1 - Zhang, Qingpeng A1 - Hou, Lei A1 - Chen, Hua A1 - Tao, Ran A1 - Huang, Zheng A1 - Fu, Zheng A1 - Chen, Ye-Guang A1 - Han, Jing-Dong J Y1 - 2006/11/24 N2 - The protein–protein interaction networks, or interactome networks, have been shown to have dynamic modular structures, yet the functional connections between and among the modules are less well understood. Here, using a new pipeline to integrate the interactome and the transcriptome, we identified a pair of transcriptionally anticorrelated modules, each consisting of hundreds of genes in multicellular interactome networks across different individuals and populations. The two modules are associated with cellular proliferation and differentiation, respectively. The proliferation module is conserved among eukaryotic organisms, whereas the differentiation module is specific to multicellular organisms. Upon differentiation of various tissues and cell lines from different organisms, the expression of the proliferation module is more uniformly suppressed, while the differentiation module is upregulated in a tissue- and species-specific manner. Our results indicate that even at the tissue and organism levels, proliferation and differentiation modules may correspond to two alternative states of the molecular network and may reflect a universal symbiotic relationship in a multicellular organism. Our analyses further predict that the proteins mediating the interactions between these modules may serve as modulators at the proliferation/differentiation switch. JF - PLOS Computational Biology JA - PLOS Computational Biology VL - 2 IS - 11 UR - https://doi.org/10.1371/journal.pcbi.0020145 SP - e145 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pcbi.0020145 ER -