Development and maintenance of bioinformatics tools for mouse biology

在我们之前的工作中，我们开发了四个主要的生物信息学工具/数据库：(1)基于web的ANOVA-FDR软件，提供用户友好的微阵列数据分析（http://lgsun.grc.nia.nih.gov/ANOVA/）；(2)从与小鼠基因组一致的表达序列中组装转录本的算法和全自动计算管道；(3)一个基于网络的浏览器，用于可视化小鼠基因的所有转录本和其他剪接形式（NIA小鼠基因索引：http://lgsun.grc.nia.nih.gov/geneindex/mm9/）；(4)基于web的数据库和工具，用于可视化和绘制小鼠基因组的转录因子结合位点（CisView: http://lgsun.grc.nia.nih.gov/geneindex/mm6/cisview.html）；(5)基于全基因组染色质免疫沉淀与测序（ChIP-Seq）方法的基于网络的共识序列基序识别工具（CisFinder: http: http://lgsun.grc.nia.nih.gov/CisFinder/）。我们还开发了一种新的算法来模拟由两个相互竞争的转录因子调控的基因表达。

In our previous work, we developed four major bioinformatics tools/databases: (1) the web-based ANOVA-FDR software to provide user-friendly microarray data analysis (http://lgsun.grc.nia.nih.gov/ANOVA/); (2) an algorithm and a fully-automated computational pipeline for transcript assembly from expressed sequences aligned to the mouse genome; (3) a web-based browser to visualize all transcripts and alternative spliced forms of mouse genes (NIA Mouse Gene Index: http://lgsun.grc.nia.nih.gov/geneindex/mm9/); (4) a web-based database and tool to visualize and map the transcription factor binding sites of the mouse genome (CisView: http://lgsun.grc.nia.nih.gov/geneindex/mm6/cisview.html); and (5) a web-based tool to identify consensus sequence motifs based on the genome-wide chromatin-immunoprecipitation coupled with sequencing (ChIP-Seq) method (CisFinder: http: http://lgsun.grc.nia.nih.gov/CisFinder/). We have also developed a new algorithm to simulate the gene expression regulated by two competing transcription factors. Utilizing the bioinformatics tools developed here, we analyzed the global gene expression profiles generated after the overexpression of specific transcriptions factors in mouse ES cells. The analyses helped to identify cis-regulatory elements for both active (i.e., bound by P300, CHD7, mediator, cohesin, and SWI/SNF) or repressed (i.e., with H3K27me3 histone marks and bound by Polycomb factors) states. These results were also used to identify most likely downstream target genes for specific transcription factors. We continued to apply our software tools to various biological problems of our own and in collaboration, which yielded a few publications. We are working constantly to maintain and update the bioinformatics resources that we have developed and made available to the research community. We will continue working on the development of new algorithms and websites for bioinformatics needs.