Deep Sequencing Instrumentation Upgrade - Illumina HiSeq2500

描述（由申请人提供）：本申请的目的是利用我们的Illumina Genome Analyzer IIx （GAIIx）下一代测序仪资产，通过申请资金购买更高通量，灵活，最先进的Illumina HiSeq2500仪器系统，来升级和更好地服务于勒纳研究所和克利夫兰诊所卫生系统研究企业的研究人员的深度测序需求。HiSeq2500仪器是Illumina系列大规模平行测序仪器中最新的一款，是美国国立卫生研究院（NIH） 1000美元基因组计划的直接成果。它具有更高的序列读取输出，具有更大灵活性的快速运行模式，能够实现更广泛的基因组规模应用，同时比GAIIx更具成本效益。就应用能力而言，HiSeq2500代表了Illumina仪器和技术进入市场的最通用的产品。基础技术可以概括为使用基于头的流式细胞与单碱基合成TruSeq v3化学进行大规模并行测序（在典型的10天高通量运行中最大输出600 Gb序列）。如申请中所述，该仪器和技术将支持我们的项目，主要包括生物标志物发现、转录组、甲基组、宏基因组和临床/转化研究，这些研究代表了我们机构的独特优势。该项目将利用HiSeq2500在规模、多功能性和更高采样复用能力方面的优势。与GAIIx相比，每个flowcell的输出读取数更高，导致RNA-seq具有更高的文库复用能力，从而减少每个样品的费用，比微阵列分析具有更好的动态范围，能够可靠地检测低丰度转录本，并为整个转录组，小RNA或非编码RNA发现和基因表达分析发现新的转录本。HiSeq2500用更少的时间完成DNA-蛋白质调控相互作用的全基因组图谱、表观遗传调控、全基因组测序、外显子组测序、在患者DNA的转化研究中对大基因组区域进行重测序，以揭示人类疾病引起的突变和人类肠道菌群的转化宏基因组研究。HiSeq2500对于将目前美国国立卫生研究院资助的项目提升到一个新的水平，并在俄亥俄州东北部培育新的努力至关重要。克利夫兰诊所已经投入了大量资源，通过在基因组医学研究所内建立lri基因组学核心，并支持其在更大的研究核心服务基础设施内的运作，以确保其长期运行和维护，从而开发转化基因组学和基因组医学。

DESCRIPTION (provided by applicant): The purpose of this application is to leverage our Illumina Genome Analyzer IIx (GAIIx) next generation sequencer asset to upgrade and better serve the deep sequencing needs of investigators within the Lerner Research Institute and the research enterprise of the Cleveland Clinic Health System by requesting funds to purchase the higher throughput, flexible, state-of-the-art, Illumina HiSeq2500 instrument system. The HiSeq2500 instrument is the latest in the Illumina suite of massively parallel sequencing instruments developed as a direct consequence of the NIH initiative for the $1,000 genome project. It has a higher sequence read output, a rapid-run mode for greater flexibility enabling a wider range of genome-scale applications while being more cost effective to run than the GAIIx. The HiSeq2500 represents the most versatile, in terms of applications capabilities, of the Illumina instruments and technologies to come to the market. The underlying technology can be summarized as massively parallel sequencing using bead-based flowcells with single base synthesis TruSeq v3 chemistry (maximum output 600 Gb of sequence in a typical 10 day high throughput run). As detailed in the application, the instrument and technology will support our projects that primarily include biomarker discovery, transcriptome, methylome, metagenome and clinical/translational studies that represent the unique strengths of our institution. The projects will take advantage of the HiSeq2500 advances of scale, versatility and higher sample multiplexing capability. Higher numbers of output reads per flowcell than the GAIIx leads to higher library multiplexing capability for RNA-seq resulting in less expense per sample, better dynamic range than microarray profiling, the ability to reliably detect low- abundance transcripts and to discover novel transcripts for whole transcriptome, small or non-coding RNA discovery and gene expression profiling. The HiSeq2500 takes less time to complete genome- wide profiles of DNA-protein regulatory interactions, epigenetic regulation, whole genome sequencing, exome sequencing, re-sequencing of large genomic regions in translational research with patient DNA to uncover human disease causing mutations and translational metagenomic studies of human gut flora. The HiSeq2500 is essential to lift the current NIH-funded projects to the next level and to seed new endeavors in northeast Ohio. Cleveland Clinic has already committed substantial resources to the development of translational genomics and genomic medicine by founding the LRI-Genomics Core within the Genomic Medicine Institute and by supporting its operation within the larger Research Core Services infrastructure to ensure its operation and maintenance for the long-term.