LAUSR

Background Different complications and stages often co-occur in the development of Type II Diabetes (T2D). The potential molecular mechanism between complications and related tissues is still not clear, thus it is crucial to characterize the common and specialty of dynamical biological processes in different responsive tissues of Type II Diabetes. Pan-tissue analyses that examine dys-regulation genes and pathways among various tissue types have emerged as a powerful way to obtain novel insights into Type II Diabetes. Considering the definite function modules (e.g. pathways) will be easier to interpret than chaotic genes, we propose a novel computational framework, Tissue Pathway Cross-talk (TPC), to recognize the functional relationship between tissue-specific and tissue-common pathways from omics data . Methods Here we present TPC investigation on pathway alterations in a pan-tissue cohort including 6 tissues (adipose, liver, Mitochondria, muscle, pancreatic beta-cells, pancreatic islets) from 17 GEO datasets, comprising pathways from KEGG, reactome, Biocarta, and wikiPathway. Using our standardized workflow, we identified betweenness-induced hub-genes from the high-order network connecting common and specific pathways in different tissues. Results After the comprehensive comparison with the previously reported milestone molecules of T2D, we found:(1) the critical function changes were identified by the tissue-specific pathways, which would be considered as a consensus phenotype-change event during T2D development and progression (table 1); (2) 28 tissue-common pathways related to T2D were significantly enriched with prior-known T2D associated genes, which would be pathway signatures of T2D regulation patterns (table 2); (3) Betweenness-induced hub-genes on pathway-network are selected as the key candidates to study the tissue diversity mechanism under the same disease/T2D condition.Abstract IDDF2019-ABS-0209 Table 1 Analysis results: The Jaccard Index of pathway intersection between any two tissues.Abstract IDDF2019-ABS-0209 Table 2 Analysis results: 28 tissue-common pathways enriched in six tissues. Conclusions Totally, we proposed a new viewpoint as pan-tissue analysis and implemented a pathway-based computational approach to detect the critical difference and common pathways in the responsive tissues during T2D progression, and also shown that the tissue-common pathways can especially serve as genetic warning signals for the T2D sub-states (e.g.complications).