Deep Sequencing Instrumentation Upgrade - Illumina HiSeq2500

描述（申请人提供）：该应用程序的目的是利用我们的Illumina基因组分析仪IIx（GAIIx）下一代测序仪资产来升级并更好地满足勒纳研究所和克利夫兰诊所卫生系统研究企业内研究人员的深度测序需求。资金购买更高通量、灵活、最先进的Illumina HiSeq 2500仪器系统。HiSeq 2500仪器是Illumina大规模并行测序仪器套件中的最新产品，该套件是NIH为1，000美元基因组计划而开发的直接结果。它具有更高的序列读取输出，快速运行模式，具有更大的灵活性，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。HiSeq 2500代表了市场上Illumina仪器和技术中应用能力最强的产品。基础技术可以概括为使用具有单碱基合成TruSeq v3化学的基于珠粒的流动池的大规模并行测序（在典型的10天高通量运行中最大输出600 Gb的序列）。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，甲基化组，宏基因组和临床/翻译研究，这些研究代表了我们机构的独特优势。这些项目将利用HiSeq 2500在规模、多功能性和更高的样本多路复用能力方面的进步。与GAIIx相比，每个流动池的输出读数数量更高，导致RNA-seq的文库多重能力更高，从而导致每个样品的费用更低，动态范围比微阵列分析更好，能够可靠地检测低丰度转录物并发现用于全转录组的新型转录物，小或非编码RNA发现和基因表达分析。HiSeq 2500花费更少的时间来完成DNA-蛋白质调控相互作用、表观遗传调控、全基因组测序、外显子组测序、在利用患者DNA的翻译研究中对大基因组区域的重测序以揭示人类致病突变和人类肠道植物群的翻译宏基因组研究的全基因组谱。HiSeq 2500对于将目前NIH资助的项目提升到一个新的水平并在俄亥俄州东北部开展新的工作至关重要。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，并通过支持其在更大的研究核心服务基础设施内的运营，以确保其长期运营和维护，来发展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.