The Cartwheel Project: Tools for Regulatory Genomics

It's been a busy few weeks, in part because I've been writing a grant. Last Thursday, I submitted a grant proposal to NIH for their program announcement, Continued Development and Maintenance of Software. The proposal was to continue maintaining Cartwheel, while integrating a new visualization frontend (MUSSA) and a fast genome-wide motif searching system based on pygr. I concentrated on making the point that building easy-to-use, correct, maintainable, and extensible software is quite tough all on its own, and that such software has real research consequences in these days of whole genomes. This will probably be read by biologists, which have a different arrogance than computational biologists; I don't know if I pitched it correctly ;). I guess we'll find out in a few months.

Anyway, here's the grant abstract. You can download the Specific Aims and Background & Significance sections here if you're interested. I would be very interested in references supporting the hypothesis generation and ease-of-use arguments...

Understanding gene regulation in detail is a goal of both developmental biology and microbial physiology, yet computational tools for investigating the function of non-coding sequence remain relatively immature. Simple, intuitive, and powerful tools that allow individual bench biologists to explore regulatory function in genomic sequence can dramatically increase experimental productivity by both generating and eliminating hypotheses. However, there are very few computational tools that let biologists generate and test hypotheses about regulatory function, even though the opportunities to integrate genomic evidence with experimental design are growing rapidly with the increasing number of sequenced genomes. In particular, there is a growing body of techniques used to predict regulatory DNA and transcription factor/DNA interactions that is essentially unusable by individual biology investigators.

The Cartwheel Project, an existing suite of integrated tools for regulatory genomics, was designed in the Davidson Lab at Caltech in order to find conserved non-coding sequences in localized genomic regions; it is now a standard tool in many labs, because Cartwheel fills the desperate need for easy-to-use genomic analysis tools. However, Cartwheel was designed before many whole genomes were available. We need to enhance and extend Cartwheel to better interact with genome databases and annotations. We also plan to provide accurate and fast multi-genome motif searching and conservation analysis, to facilitate the use of multiple pieces of evidence in hypothesis generation. Finally, we need to continue maintaining the existing tools, and we also need to develop more educational materials on regulatory genomics in order to better support informed research with our tools.

Because transcriptional and post-transcriptional gene regulation is part of almost every biological process, tools to help biologists better study gene regulation will benefit the study of development, physiology, and disease.

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