Figure 2: Algorithm for detecting early warning signal of a critical transition. From: Detecting tissue-specific early warning signals for complex diseases.

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Figure 2: Algorithm for detecting early warning signal of a critical transition. From: Detecting tissue-specific early warning signals for complex diseases based on dynamical network biomarkers: study of type 2 diabetes by cross-tissue analysis Brief Bioinform. 2013;15(2):229-243. doi:10.1093/bib/bbt027 Brief Bioinform | © The Author 2013. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com

Figure 1: Differences between traditional molecular biomarker and dynamical network biomarker (DNB). (A) schematically illustrates the stages and progression of a complex disease. (B) indicates the differences between traditional molecular biomarker and DNB. Dynamical network biomarker explores the dynamical information of molecular fluctuations as well as the correlations between molecules (or network information), which is a new concept on biomarkers from both theoretical and biomedical viewpoints. Note that we focus on Pre-transition state (Pre-disease state), and thus Early-transition state (Early-disease state) is not analyzed in this paper, which is considered as similar to After-transition state (Disease state). From: Detecting tissue-specific early warning signals for complex diseases based on dynamical network biomarkers: study of type 2 diabetes by cross-tissue analysis Brief Bioinform. 2013;15(2):229-243. doi:10.1093/bib/bbt027 Brief Bioinform | © The Author 2013. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com

Figure 3: The composition index (A) and the DNB (B) for each tissue of GK rats. L1 and L4 are DNBs of liver at the first period (4 weeks) and the fourth period (16 weeks), respectively. M1 and M4 are DNBs of muscle at the first period (4 weeks) and the fourth period (16 weeks), respectively. A2 is the DNB of adipose at the second period (8 weeks). (C) visually illustrates dynamics of the identified DNBs compared with the whole molecular network. From: Detecting tissue-specific early warning signals for complex diseases based on dynamical network biomarkers: study of type 2 diabetes by cross-tissue analysis Brief Bioinform. 2013;15(2):229-243. doi:10.1093/bib/bbt027 Brief Bioinform | © The Author 2013. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com

Figure 4: Key biological pathways with DNB genes and differentially expressed genes (DEG). Clearly, DNB genes are placed at the important positions in the pathways, i.e. core genes of the DNB are mainly located at the upstream to regulate DEG. From: Detecting tissue-specific early warning signals for complex diseases based on dynamical network biomarkers: study of type 2 diabetes by cross-tissue analysis Brief Bioinform. 2013;15(2):229-243. doi:10.1093/bib/bbt027 Brief Bioinform | © The Author 2013. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com