title: Spatio-temporal analysis of type 2 diabetes mellitus based on differential expression networks.
abstract: T2DM is complex in its dynamical dependence on multiple tissues, disease states, and factors' interactions. However, most existing work devoted to characterizing its pathophysiology from one static tissue, individual factors, or single state. Here we perform a spatio-temporal analysis on T2DM by developing a new form of molecular network, i.e. 'differential expression network' (DEN), which can reflect phenotype differences at network level. Static DENs show that three tissues (white adipose, skeletal muscle, and liver) all suffer from severe inflammation and perturbed metabolism, among which metabolic functions are seriously affected in liver. Dynamical analysis on DENs reveals metabolic function changes in adipose and liver are consistent with insulin resistance (IR) deterioration. Close investigation on IR pathway identifies 'disease interactions', revealing that IR deterioration is earlier than that on SlC2A4 in adipose and muscle. Our analysis also provides evidence that rising of insulin secretion is the root cause of IR in diabetes.
authors.affiliation: Key Laboratory of Systems Biology, SIBS-Novo Nordisk Translational Research Centre for PreDiabetes, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Shao-Yan
authors.initials: SY
authors.lastname: Sun
authors.forename: Zhi-Ping
authors.initials: ZP
authors.lastname: Liu
authors.forename: Tao
authors.initials: T
authors.lastname: Zeng
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Luonan
authors.initials: L
authors.lastname: Chen
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D016000:Cluster Analysis; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D008099:Liver / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D059467:Transcriptome