ABI Innovation: Building a Comprehensive Catalog of Conserved Alternative Splicing Events from Heterogeneous Data

授予马里兰州大学帕克分校一笔赠款，以开发一种方法，用于从异质序列数据中构建保守的选择性剪接事件目录。选择性剪接（AS）是高等生物中广泛存在的一种可能的普遍机制。单个基因可以被拼接成多个变体，每个变体能够在不同的细胞条件下产生不同的功能，例如不同的组织或发育阶段，这有可能解释复杂的生物体如何通过重复使用相对较少的基因而进化。因此，创建一个全面的AS变异目录是了解一个物种生物学的关键一步，到目前为止，这一步骤受到数据可用性的限制。该项目将建立第一种方法和支持计算基础设施，通过整合异质序列数据（包括来自RNA-seq实验的数据），在物种内和物种间构建AS事件的综合目录。 这项研究将为如何分析大量的异质数据以检测AS变异并在物种之间有效准确地绘制它们提供重要的见解。它将产生新的软件工具，可以无缝地将各种类型的序列数据与目标基因组进行比对，并将使用它们来构建基因及其剪接变体的模型，并在物种之间绘制它们。该方法将结合联合收割机比较基因组学方法与序列和比对的统计模型，并与新的计算生物学概念，如剪接图。该项目将创建强大的生物信息学工具，帮助生物学家分析RNA-seq数据，并为其他物种（包括动物、昆虫和植物）创建类似的数据库。(All工具将作为开源软件免费发布。）收集的保守和物种特异性的事件将是一个宝贵的资源，以支持剪接进化和剪接调控的研究。此外，该项目还将创建电子资源，以支持计算机科学和生物学方面的交叉教育，包括将在马里兰州大学的课程中使用的基于网络的生物信息学模块，并将通过国家实验室日论坛向科学教育专业人士提供这些模块。最后，它将通过暑期实习为从高中到研究生的学生创造培训和教育机会。 该项目的数据库、结果和软件可从http://cbcb.umd.edu/~florea/research/上查阅。

A grant is awarded to the University of Maryland, College Park to develop a methodology for building catalogs of conserved alternative splicing events from heterogeneous sequence data. Alternative splicing (AS) is a widespread, likely universal mechanism in higher organisms. A single gene can be spliced into multiple variants, each capable of producing different functionality under different cell conditions, for instance different tissues or developmental stages, which has the potential to explain how complex organisms evolve by re-using a relatively small number of genes. Creating a comprehensive catalog of AS variations is therefore a critical step in understanding the biology of a species, one which has been limited so far by the availability of data. This project will establish the first methodology and the supporting computational infrastructure for building comprehensive catalogs of AS events within and between species by integrating heterogeneous sequence data, including those from RNA-seq experiments. This research will provide critical insights into how to analyze the massive amounts of heterogeneous data to detect AS variations and map them efficiently and accurately between species. It will produce novel software tools that can seamlessly align the various types of sequence data to a target genome, and will use them to construct models of genes and their splice variants and map them between species. The methods will combine comparative genomics approaches with statistical models of sequences and alignments, and with novel computational biology concepts such as the splice graph. The project will create powerful bioinformatics tools to help biologists analyze RNA-seq data and create similar repositories for other species, including animals, insects and plants. (All tools will be released free of charge as open source software.) The collection of conserved and species-specific events will be an invaluable resource to support studies of splicing evolution and splicing regulation. Additionally, the project will create electronic resources to support cross-cutting education in computer science and biology, including web-based bioinformatics modules that will be used in the curriculum at the University of Maryland and will also be made available to the community of science education professionals through the National Lab Day forum. Lastly, it will create opportunities for training and education of students from high-school through graduate levels through Summer internships. The database, results and software for this project will be accessible from http://cbcb.umd.edu/~florea/research/ .