An extensive and dynamic trans-omic network illustrating prominent regulatory mechanisms in response to insulin in the liver
Fumiko Matsuzaki,
Shinsuke Uda,
Yukiyo Yamauchi,
Masaki Matsumoto,
Tomoyoshi Soga,
Kazumitsu Maehara,
Yasuyuki Ohkawa,
Keiichi I. Nakayama,
Shinya Kuroda,
Hiroyuki Kubota
Affiliations
Fumiko Matsuzaki
Research Center for Transomics Medicine, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582, Japan
Shinsuke Uda
Research Center for Transomics Medicine, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582, Japan
Yukiyo Yamauchi
Research Center for Transomics Medicine, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582, Japan
Masaki Matsumoto
Department of Omics and Systems Biology, Graduate School of Medical and Dental Sciences, Niigata University, 757 Ichibancho, Asahimachi-dori, Chuo-ku, Niigata 951-8510, Japan
Tomoyoshi Soga
Institute for Advanced Biosciences, Keio University, 246-2 Mizukami, Kakuganji, Tsuruoka, Yamagata 997-0052, Japan
Kazumitsu Maehara
Research Center for Transomics Medicine, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582, Japan
Yasuyuki Ohkawa
Research Center for Transomics Medicine, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582, Japan
Keiichi I. Nakayama
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582, Japan
Shinya Kuroda
Department of Biological Sciences, Graduate School of Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
Hiroyuki Kubota
Research Center for Transomics Medicine, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582, Japan; Corresponding author
Summary: An effective combination of multi-omic datasets can enhance our understanding of complex biological phenomena. To build a context-dependent network with multiple omic layers, i.e., a trans-omic network, we perform phosphoproteomics, transcriptomics, proteomics, and metabolomics of murine liver for 4 h after insulin administration and integrate the resulting time series. Structural characteristics and dynamic nature of the network are analyzed to elucidate the impact of insulin. Early and prominent changes in protein phosphorylation and persistent and asynchronous changes in mRNA and protein levels through non-transcriptional mechanisms indicate enhanced crosstalk between phosphorylation-mediated signaling and protein expression regulation. Metabolic response shows different temporal regulation with transient increases at early time points across categories and enhanced response in the amino acid and nucleotide categories at later time points as a result of process convergence. This extensive and dynamic view of the trans-omic network elucidates prominent regulatory mechanisms that drive insulin responses through intricate interlayer coordination.
