Development of Celera Whole Genome Shotgun Assembler

描述（由申请人提供）：该资助的目标是提高基因组界准确、轻松、快速地从鸟枪测序数据中组装基因组序列的能力。具体来说，我们计划增强和维护一个领先的霰弹枪碎片组装软件程序，Celera Assembler。猎枪DNA序列数据的生成速度比精确组装以确定基因组序列的速度还要快。随着能够以低成本产生大量序列数据的新型测序仪投入使用，这个问题只会变得更加复杂。装配软件的复杂性继续受到挑战，以跟上步伐。Celera Assembler于2004年发布到公共领域，并通过Sourceforge存储库作为一个开源项目进行管理。装配软件的质量和准确性直接影响到基因组测序项目和基因组闭合的成本，而最终基因组序列的准确性直接影响到利用该序列的所有与健康相关的研究。我们已经组建了一支优秀的团队，其中包括原始开发团队的很大一部分，以改进和维护Celera Assembler，并支持其用户群。首席研究员是Celera汇编器开发的联合负责人，三位共同研究员都对算法和代码库做出了重大贡献。该团队已经证明，对Celera组装器的增强可以显著提高基因组组装的质量（11,41）。这笔拨款将使我们能够使Celera汇编程序更加用户友好，健壮，能够生成更高质量的汇编程序，并结合来自新型测序器的数据。为此，我们将简化和改进算法和代码，开发或合并分析工具来评估组件的质量，在多个计算机平台上测试代码，在众多生物组件上调试代码，并开发一套基于真实数据的具有挑战性的基准组装问题，用于严格的回归测试，以验证使用改进算法的改进结果。所有算法的改进都将在科学文献中发表，并在代码库中记录。整个代码库以及支持的分析、基准测试和回归工具将作为一个开源项目进行维护。

DESCRIPTION (provided by applicant): The goal of this grant is to advance the genomic community's ability to accurately, easily and rapidly assemble genome sequences from shotgun sequencing data. Specifically, we plan to enhance and maintain a leading shotgun fragment assembly software program, the Celera Assembler. Shotgun DNA sequence data continues to be produced faster than it can accurately be assembled to determine genomic sequence. This problem will only be compounded as new sequencing machines, capable of producing large volumes of sequence data at low cost, come into active use. The sophistication of assembly software continues to be challenged to keep pace. The Celera Assembler was released into the public domain in 2004, and is managed as an open source project via the Sourceforge repository. The quality and accuracy of assembly software has a direct impact on the cost of genomic sequencing projects and genome closure, and the accuracy of the resulting genome sequence has a direct impact on all of the health related research that utilizes the sequence. We have assembled an exceptional team comprising a large portion of the original development team to improve and maintain the Celera Assembler, and support its user base. The principal investigator was the co-leader of the Celera Assembler development at Celera and the three co-investigators all made significant contributions to the algorithms and code base. This team has demonstrated that enhancements to the Celera Assembler could significantly improve the quality of genome assemblies (11, 41). This grant will allow us to make the Celera Assembler more user friendly, robust, capable of generating higher quality assemblies, and incorporating data from new types of sequencers. Towards this end, we will simplify and improve the algorithms and code, develop or incorporate analysis tools to assess the quality of assemblies, test the code on multiple computer platforms, debug the code on numerous organism assemblies, and develop a set of challenging benchmark assembly problems based on real data for use in rigorous regression testing to validate improved results using improved algorithms. All algorithmic improvements will be published in the scientific literature and documented in the code base. The entire code base and supporting analysis, benchmark and regression tools will be maintained as an open source project.