Understanding tissue-specificity with human tissue-specific regulatory networks  

作　　者：Weili GUO Lin ZHU Suping DENG Xingming ZHAO Deshuang HUANG 

机构地区：[1]College of Electromics and Information Engineering, Tongji University

出　　处：《Science China(Information Sciences)》2016年第7期47-56,共10页中国科学（信息科学）（英文版）

基　　金：supported by National Natural Science Foundation of China (Grant Nos. 61520106006, 31571364, 61532008, 61411140249, 61133010, 91529303, 61572363);Innovation Program of Shanghai Municipal Education Commission (Grant No. 13ZZ072);Shanghai Pujiang Program (Grant No. 13PJD032);Ph.D. Programs Foundation of Ministry of Education of China (Grant No. 20120072110040);Fundamental Research Funds for the Central Universities;Special Program for Applied Research on Super Computation of the NSFC-Guangdong Joint Fund (the second phase)

摘　　要：Tissue-specificity is important for the function of human body. However, it is still not clear how the functional diversity of different tissues is achieved. Here we construct gene regulatory networks in 13 human tissues by integrating large-scale transcription factor （TF）-gene regulations with gene and protein expression data. By comparing these regulatory networks, we find many tissue-specific regulations that are important for tissue identity. In particular, the tissue-specific TFs are found to regulate more genes than those expressed in multiple tissues, and the processes regulated by these tissue-specific TFs are closely related to tissue functions. Moreover, the regulations that are present in certain tissue are found to be enriched in the tissue associated disease genes, and these networks provide the molecular context of disease genes. Therefore, recognizing tissue- specific regulatory networks can help better understand the molecular mechanisms underlying diseases and identify new disease genes.Tissue-specificity is important for the function of human body. However, it is still not clear how the functional diversity of different tissues is achieved. Here we construct gene regulatory networks in 13 human tissues by integrating large-scale transcription factor （TF）-gene regulations with gene and protein expression data. By comparing these regulatory networks, we find many tissue-specific regulations that are important for tissue identity. In particular, the tissue-specific TFs are found to regulate more genes than those expressed in multiple tissues, and the processes regulated by these tissue-specific TFs are closely related to tissue functions. Moreover, the regulations that are present in certain tissue are found to be enriched in the tissue associated disease genes, and these networks provide the molecular context of disease genes. Therefore, recognizing tissue- specific regulatory networks can help better understand the molecular mechanisms underlying diseases and identify new disease genes.

关 键 词：TISSUE-SPECIFICITY gene regulatory network transcription factor tissue-specific regulation disease gene 

分 类 号：R346[医药卫生—基础医学]