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/ .
