APG: an Active Protein-Gene network model to quantify regulatory signals in complex biological systems.
Synergistic interactions among transcription factors (TFs) and their cofactors collectively determine gene expression in complex biological systems. In this work, we develop a novel graphical model, called Active Protein-Gene (APG) network model, to quantify regulatory signals of transcription in complex biomolecular networks through integrating both TF upstream-regulation and downstream-regulation high-throughput data. Firstly, we theoretically and computationally demonstrate the effectiveness of APG by comparing with the traditional strategy based only on TF downstream-regulation information. We then apply this model to study spontaneous type 2 diabetic Goto-Kakizaki (GK) and Wistar control rats. Our biological experiments validate the theoretical results. In particular, SP1 is found to be a hidden TF with changed regulatory activity, and the loss of SP1 activity contributes to the increased glucose production during diabetes development. APG model provides theoretical basis to quantitatively elucidate transcriptional regulation by modelling TF combinatorial interactions and exploiting multilevel high-throughput information.
Key Laboratory of Systems Biology, SIBS-Novo Nordisk Translational Research Centre for PreDiabetes, Shanghai Institutes for Biological Sciences, CAS, Shanghai 200233, China.
Jiguang
J
Wang
Yidan
Y
Sun
Si
S
Zheng
Xiang-Sun
XS
Zhang
Huarong
H
Zhou
Luonan
L
Chen
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D053263:Gene Regulatory Networks / Q000235:genetics*; D005947:Glucose / Q000235:genetics / Q000378:metabolism; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism; D008297:Male; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic
D007136:Immunoglobulins; D011506:Proteins; C090698:SP1 antigen; D014157:Transcription Factors; D005947:Glucose