The Terabase Search Engine

描述（由申请人提供）：我们建议创建一个新的系统，Terabase搜索引擎，这将使生物医学研究人员能够搜索所有已测序并存放在公共档案中的人类DNA序列。人类DNA序列的巨大和不断增长的资源为科学发现和结果验证提供了丰富的机会，但是数据集的规模已经远远超过了大多数研究人员使用它们的能力。二十多年来，遗传学家和遗传学家依靠DNA序列数据库进行广泛的科学研究，包括发现新基因和新突变，研究物种内部和物种之间的进化变化，影响染色体结构和变化的力量，以及许多其他分子和进化过程。使用BLAST和类似程序搜索所有已知基因和基因组的能力早已被假设，全世界的序列搜索引擎都提供了这种能力。然而，从下一代测序（NGS）项目中涌出的原始数据已经超出了我们提供快速访问的能力。一台单一的NGS仪器可以在一次运行中产生60亿次读取，包含6000亿个碱基，而且这种能力还在不断增长。像BLAST这样的传统对齐程序不能在合理的时间内对这些数据进行排序。更新，更快的程序，如Bowtie（由我们的团队开发）可以更快地将NGS读取到基因组，但是今天的数据集的大小，现在超过1万亿的读取，远远超过了大多数计算机存储它的能力。和

DESCRIPTION (provided by applicant): We propose to create a new system, the Terabase Search Engine that will make it possible for biomedical researchers to search all human DNA sequences that have been sequenced and deposited in public archives. The vast and growing resource of human DNA sequences provides a wealth of opportunities for scientific discovery and for validation of results, but the size of the data sets has already far exceeded the ability o most researchers to use them. For more than two decades, geneticists and geneticists have relied on DNA sequence databases for a wide range of scientific endeavors, including the discovery of new genes and new mutations, the investigation of evolutionary changes within and between species, the forces affecting chromosomal structure and change, and many other molecular and evolutionary processes. The ability to search all known genes and genomes using BLAST and similar programs has long been assumed, and sequence search engines throughout the world provide this ability. However, the raw data pouring out of next-generation sequencing (NGS) projects has exceeded our ability to provide rapid access to it. A single NGS instrument can generate six billion reads encompassing 600 billion bases in a single run, and this capacity is still growing. Traditional alignment programs like BLAST cannot sort through this data in a reasonable amount of time. Newer, faster programs such as Bowtie (developed by our group) allow far faster alignment of NGS reads to the genome, but today the size of the data sets, now in excess of 1 trillion reads, far exceeds the ability of most computers to store it. And even the fastest alignment programs today could not search all this data in a reasonable amount of time. A new approach is required in order to serve up these huge and hugely valuable DNA sequences to the research community. The Terabase Search Engine will be a new, highly efficient system for searching trillions of bases in real time. Using a hierarchical search strategy with extensive pre-processing to speed up response time, the TSE will allow a scientist to align any sequence, human or non-human, to all publicly-available human sequence reads. Reads that match the human genome will be indexed and stored on very high-speed disks for rapid retrieval. Reads that match microbial sequences will be captured and stored separately for use in micro biome and infectious disease research. The system will be made available through a user-friendly web interface, and a local database will store each user's results for further analysis on the TSE site or for download to a local site. This system will make it possible, for the first time ever, for any scientist to align a sequence to the complete set of human DNA sequences and to retrieve everything that matches, without the need to write special-purpose programs or to use complex cloud-based software interfaces. All of the software for this project will be developed under an open-source model that will permit others to use, modify, share, and re-distribute the code without restriction.