Honors Program: Iowa State University

Project Name: Cracking the Corn Genome Code

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Difficulty

What were the most important obstacles that had to be overcome in order for your work to be successful? Technical problems? Resources? Expertise? Organizational problems?

The project had to overcome the usual obstacles that are part of undertaking any academic research project: intellectual challenges and raising funds to support the project. As it is difficult to obtain funding for supporting professional software engineers, the development work has to be carried out by graduate students. At the beginning of the project, it was not clear if the intellectual challenges could be overcome. There have been nearly a dozen previous efforts that developed assemblers based on storing all pairwise relationships between DNA fragments. The planned project is aimed at avoiding this storage to enable analyzing large-scale data, develop faster methods and provide scaling to a large number of processors.

Conventional assemblers work well for genomes with manageable repeats that are uniformly sampled, such as the highly visible and successful human and mouse genome projects. The maize genome is highly repetitive, with 65% to 80% estimated repeat content. The NSF-funded gene-enriched sequencing provided a biased sampling of the gene-rich regions. These, together with repeat fragments that survive, create an unusually large number of pairwise overlaps that would fail conventional strategies. This timely and challenging problem provided a powerful venue for demonstrating the utility and impact of the project.

Often the most innovative projects encounter the greatest resistance when they are originally proposed. If you had to fight for approval or funding, please provide a summary of the objections you faced and how you overcame them.

The project was initially funded by the NSF, after two rounds of unsuccessful attempts at securing funding. Because the project proposed a radically different approach, reviewers expected a convincing plan and in-depth preliminary investigations. These were addressed by more fully developing some of the key ideas behind the project, a thorough experimental evaluation of the weaknesses of some of the most popular existing software, and how the project would overcome them. Still, funding was provided at a reduced level due to doubts about whether the project will lead to software that will be found useful and adopted. IBM has gracefully provided access to Blue Gene/L experimental platforms at its Rochester facility. This was instrumental in demonstrating the high degree of scalability of the software and in applying it to maize. After the success in demonstrating the software to develop genome assemblies from NSF-funded pilot projects at a rapid pace using the Blue Gene/L, Iowa State researchers sought funding from NSF to purchase a Blue Gene/L system to work on the NSF/USDA/DOE maize genome sequencing project. This effort was immediately successful. However, further financial resources were required to make the purchase. Significant efforts to raise matching internal funds from various university sources and a strong and continuing partnership with IBM were instrumental in overcoming the resource problem.

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