Application of Bioinformatics to Retinal Gene Regulation

描述（由申请人提供）：本提案的总体目标是使用生物信息学方法来帮助破译与视网膜基因表达相关的转录调控网络。为此，我们将开发两种算法：一种用于发现顺式调控基序，另一种用于预测转录因子靶点。具体目的1是寻找与视网膜表达相关的新的调控基序。为此，我们将开发一种新的基序发现算法，该算法将考虑基序复杂性和基序相对于转录起始位点的位置。通过将该程序应用于在视网膜中优先表达的上游基因序列，我们期望检测到新的视网膜相关基序。特异性目的2是确定视网膜转录因子的调控靶点。我们建议开发一个调控靶标预测程序，该程序将搜索多个转录因子的结合位点，并且需要这些结合位点的特定相对位置。通过这个程序，我们希望增加预测的特异性。我们将把这个程序应用于视网膜相关的转录因子和在Aim 1中检测到的基序。具体目标3是整合微阵列数据与监管网络。我们将探索基因表达与调控网络之间的关系，并将微阵列数据整合到转录因子靶点预测程序中。从这项研究中获得的结果应该有助于指导湿实验室实验，并且对视网膜调节网络的了解的增加可能会对更好地理解视网膜的发育、功能和疾病产生影响。

DESCRIPTION (provided by applicant): The overall goal of this proposal is to use a bioinformatics approach to help decipher the transcriptional regulatory networks associated with retinal gene expression. To this end, we will develop two algorithms: one for discovering cis-regulatory motifs and another for predicting transcription factor targets. Specific Aim 1 is to find novel regulatory motifs associated with retinal expression. For this aim, we will develop a new algorithm for motif discovery, one that takes into account motif complexity and motif location relative to the transcription start site. By applying this program to the upstream sequences of genes that are preferentially expressed in the retina, we expect to detect novel retina-related motifs. Specific Aim 2 is to identify the regulatory targets of retinal transcription factors. We propose to develop a regulatory target-prediction program that will search the binding sites of multiple transcription factors and that requires the specific relative location of these binding sites. With this program we hope to increase the specificity of the prediction. We will apply the program to retina-related transcription factors and the motifs detected in Aim 1. Specific Aim 3 is to integrate microarray data with the regulatory networks. We will explore the relationship between gene expression and the regulatory network, and we will integrate microarray data into the program for prediction of transcription factor targets. Results obtained from this proposed study should be useful for guiding wet-lab experiments, and the increased knowledge about the retinal regulatory network will likely have implications for better understanding of retinal development, function, and disease.