computational modelling of genome-side transcription assembly networks using a fluidics analogy计算造型genome-side转录装配网络使用流体类比.pdfVIP

Computational Modelling of Genome-Side Transcription Assembly Networks Using a Fluidics Analogy 1¤ 2 3 Yousry Y. Azmy , Anshuman Gupta , B. Franklin Pugh * 1 Department of Mechanical and Nuclear Engineering, The Pennsylvania State University, University Park, Pennsylvania, United States of America, 2 Department of Academic Services Emerging Technologies, The Pennsylvania State University, University Park, Pennsylvania, United States of America, 3 Center for Gene Regulation, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania, United States of America Abstract Understanding how a myriad of transcription regulators work to modulate mRNA output at thousands of genes remains a fundamental challenge in molecular biology. Here we develop a computational tool to aid in assessing the plausibility of gene regulatory models derived from genome-wide expression profiling of cells mutant for transcription regulators. mRNA output is modelled as fluid flow in a pipe lattice, with assembly of the transcription machinery represented by the effect of valves. Transcriptional regulators are represented as external pressure heads that determine flow rate. Modelling mutations in regulatory proteins is achieved by adjusting valves’ on/off settings. The topology of the lattice is designed by the experimentalist to resemble the expected interconnection between the modelled agents and their influence on mRNA expression. Users can compare multiple lattice configurations so as to find the one that minimizes the error with experimental data. This computational model provides a means to test the plausibility of transcription regulation models derived from large genomic data sets