Integrated Assembly Software for Sanger and Next Generation Sequence Technologies

描述（由申请人提供）：获得从细菌到人类的生物体的完整基因组DNA序列是20世纪科学的一项标志性成就，对生物科学和医学实践产生了巨大影响。序列组装软件在实现这一目标方面发挥了关键作用。现在，由于革命性的新型测序机器的出现，序列数据采集的成本有了一个新的快速和戏剧性的下降，这些机器可以以很少的成本获得大量的数据。这开启了第二波更大规模的测序浪潮，并开辟了许多新的应用，除了测序新的基因组之外，这是迄今为止无法想象的，也无法实现的。诸如使用全基因组“快照”来识别进化过程中发生的关键序列变化、对群落进行宏基因组测序以及能够帮助追踪与疾病相关的基因组DNA变化的医学诊断应用等项目都变得可行。医学科学家和企业家们甚至梦想着这样一个时代：用1000美元就能确定完整的人类基因组，尽管这还需要等待序列数据获取方面的另一个革命性进步。利用当前大量的新数据需要在汇编软件性能方面取得相应的进步。我们在此建议开发和评估可以利用所有新数据收集技术的原型软件方法。这就需要开发新的算法，利用生成的大量数据来克服瓶颈，这些瓶颈以前限制了装配的准确性和完整性，需要昂贵的人工干预来纠正。作为一家独立的软件开发商，没有特定的技术方法，DNASTAR的独特定位是提供一个值得信赖的实现，可以有效地结合来自所有方法的数据，使研究人员可以自由地使用最适合他们需求的任何技术组合。我们提出的新软件技术将大大提高重复处理、脚手架排序和注释的效率，并且我们预测装配的速度也将大大提高。这些可行性实验将在DNASTAR的高性能SeqMan基因组组装平台的坚实基础上进行。这将最大限度地提高II期后出现强大的、具有商业吸引力的产品的可能性，该产品具有政府资助的大型测序中心、商业和临床测序操作以及个人研究实验室所需的高性能和准确性。我们正在进入一个新的医学时代，在这个时代中，疾病的遗传基础将在一般公众一级和个人一级得到确定。这在一定程度上是由于破译大量DNA的能力有了显著提高，而且成本大大降低。该提案旨在开发将大量编码数据转换为医学有用信息所需的计算软件。

DESCRIPTION (provided by applicant): Obtaining complete genome DNA sequences of organisms from bacteria to man is a hallmark achievement of 20th century science and has had a huge impact on the biological sciences as well as the practice of medicine. Sequence assembly software played a critical role in making this possible. Now, there is a new rapid and dramatic fall in the cost of sequence data acquisition due to the emergence of revolutionary new sequencing machines that can turn out data in great quantities for a fraction of the cost. This is initiating a second wave of sequencing on a far greater scale and opens up many new applications, in addition to sequencing new genomes, that were heretofore not dreamed of or too costly to carry out. Projects such as using whole genome "snapshots" to identify crucial sequence changes that occur during evolution, metagenomic sequencing of communities, and medical diagnostic applications that can help track down alterations in genomic DNA related to disease are all becoming feasible. Medical scientists and entrepreneurs are even dreaming of the time when complete human genomes can be determined for about $1000, although this awaits yet another revolutionary advance in sequence data acquisition. Utilizing the present flood of new data will require corresponding progress in assembly software performance. We propose here to develop and evaluate prototype software approaches that can take advantage of all the new data gathering techniques. This will require developing new algorithms that take advantage of the abundant data generated to overcome bottlenecks that have previously limited the accuracy and completeness of assemblies necessitating expensive manual intervention to correct. As an independent software developer without vested ties to particular technical approaches, DNASTAR is uniquely positioned to provide a trusted implementation that can effectively combine data from all approaches allowing researchers the freedom to use whatever combination of technologies that best fits their needs. Our proposed new software techniques will make repeat handling, scaffold ordering and annotation far more efficient, and we predict the speed of assembly will also be increased dramatically. These feasibility experiments will be conducted on the strong foundation of DNASTAR's high performance SeqMan Genome Assembler platform. This will maximize the probability that a robust, commercially attractive product will emerge after Phase II with the high performance and accuracy needed by the large government sponsored sequencing centers, commercial and clinical sequencing operations as well as by individual research laboratories. We are embarking on a new era in medicine in which the genetic basis for diseases will be determined, both at the general public level and as individuals. This is being made possible, in part, by dramatic improvements in the ability to decipher vast amounts of DNA at a greatly reduced cost. This proposal aims to develop the computational software needed to convert that mass of coded data into medically useful information.