99.99% Accuracy Direct DNA Sequencing via the Protein Nanopore Method
99.99%%20准确度%20直接%20DNA%20测序%20via%20the%20蛋白质%20纳米孔%20方法
基本信息
- 批准号:7923364
- 负责人:
- 金额:$ 162.13万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-09-01 至 2013-06-30
- 项目状态:已结题
- 来源:
- 关键词:AlgorithmsAmino Acid SequenceAwardBackBase SequenceBasic ScienceBiological ProcessCodeComplexCustomDNADNA Modification ProcessDNA SequenceDataData AnalysesDevicesDiagnosticDiffusionElectrolytesElectronicsElementsError SourcesForensic MedicineGenomeGrantHemolysinIntegral Membrane ProteinLinkLipid BilayersLocationMeasurementMeasuresMedicalMethodsModelingModificationMotionMutationNoisePeptide Sequence DeterminationPerformancePolymersPore ProteinsProcessProteinsProtocols documentationRelative (related person)ResearchSamplingSchemeSignal TransductionSingle-Stranded DNASiteSite-Directed MutagenesisStructureSystemTechnologyTestingVariantbasebiological researchcostinsightinstrumentationmathematical modelnanoporeoperationprogramspublic health relevancereconstructionresearch studyresponsesimulationstatisticsvoltage
项目摘要
DESCRIPTION (provided by applicant): Our aim is to develop a DNA sequencing device based upon the blockade of ionic current in the transmembrane protein pore a-hemolysin (aHL). Compared to other proposed nanopore-based approaches, the protein pore current blockade (PPCB) method is arguably the simplest, both conceptually and technologically, but recently has been passed over in favor of more complex methods. Recent electronic readout and bilayer lipid membrane advances by the proposers have greatly alleviated prior signal-to-noise ratio and robustness issues. New experimental data and an accurate Stochastic Model for DNA Motion (SMDM) within a-HL now indicate threshold feasibility for sequencing by the PPCB method. Inspection of calculated SMDM responses to known input DNA sequences shows that the principal issue for sequencing via the PPCB method is random variance in the order the bases pass through the pore, leading to three quantifiable sources of error. This program will make specific structural and measurement parameter modifications to the present apparatus to reduce each type of error and to produce a minimal overall sequencing error. The final apparatus will be evaluated by sequencing up to 30 Mbases of natural DNA.
PUBLIC HEALTH RELEVANCE: This project offers a path to low cost DNA sequencing. Determining the DNA sequence is useful in basic research studying fundamental biological processes, as well as in applied fields such as diagnostic or forensic research. The advent of DNA sequencing has significantly accelerated biological research and discovery, but current methods are complicated and expensive, thus limiting their applicability. Simple, inexpensive DNA sequencing offers the capability to apply the benefits of the process to everyday medical and forensic applications.
描述(由申请人提供):我们的目标是开发一种基于跨膜蛋白孔α-溶血素(aHL)中离子电流阻断的DNA测序装置。与其他提出的基于纳米孔的方法相比,蛋白质孔电流阻断(PPCB)方法在概念上和技术上都可以说是最简单的,但最近已被更复杂的方法所取代。提议者最近在电子读出和双层脂质膜方面的进展极大地缓解了先前的信噪比和鲁棒性问题。新的实验数据和 a-HL 内准确的 DNA 运动随机模型 (SMDM) 现在表明通过 PPCB 方法进行测序的阈值可行性。对计算出的 SMDM 对已知输入 DNA 序列的响应进行检查表明,通过 PPCB 方法进行测序的主要问题是碱基通过孔的顺序的随机方差,从而导致三个可量化的误差源。该程序将对本装置进行特定的结构和测量参数修改,以减少每种类型的错误并产生最小的总体测序错误。最终的装置将通过对多达 30 Mbases 的天然 DNA 进行测序来进行评估。
公共健康相关性:该项目提供了一条低成本 DNA 测序的途径。确定 DNA 序列对于研究基本生物过程的基础研究以及诊断或法医研究等应用领域非常有用。 DNA测序的出现极大地加速了生物学研究和发现,但目前的方法复杂且昂贵,从而限制了它们的适用性。简单、廉价的 DNA 测序能够将该过程的优势应用于日常医疗和法医应用。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Geoffrey Barrall其他文献
Geoffrey Barrall的其他文献
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{{ truncateString('Geoffrey Barrall', 18)}}的其他基金
Nanopatch System for Next Generation Ion Channel Recordings
用于下一代离子通道记录的 Nanopatch 系统
- 批准号:
8058564 - 财政年份:2011
- 资助金额:
$ 162.13万 - 项目类别:
Nanopatch System for Next Generation Ion Channel Recordings
用于下一代离子通道记录的 Nanopatch 系统
- 批准号:
8332307 - 财政年份:2011
- 资助金额:
$ 162.13万 - 项目类别:
99.99% Accuracy Direct DNA Sequencing via the Protein Nanopore Method
99.99%%20准确度%20直接%20DNA%20测序%20via%20the%20蛋白质%20纳米孔%20方法
- 批准号:
8112744 - 财政年份:2009
- 资助金额:
$ 162.13万 - 项目类别:
99.99% Accuracy Direct DNA Sequencing via the Protein Nanopore Method
99.99%%20准确度%20直接%20DNA%20测序%20via%20the%20蛋白质%20纳米孔%20方法
- 批准号:
8520466 - 财政年份:2009
- 资助金额:
$ 162.13万 - 项目类别:
99.99% Accuracy Direct DNA Sequencing via the Protein Nanopore Method
99.99%%20准确度%20直接%20DNA%20测序%20via%20the%20蛋白质%20纳米孔%20方法
- 批准号:
8318888 - 财政年份:2009
- 资助金额:
$ 162.13万 - 项目类别:
99.99% Accuracy Direct DNA Sequencing via the Protein Nanopore Method
99.99%%20准确度%20直接%20DNA%20测序%20via%20the%20蛋白质%20纳米孔%20方法
- 批准号:
7714702 - 财政年份:2009
- 资助金额:
$ 162.13万 - 项目类别:
New Platform for Ionic Current Measurement with Application to DNA Sequencing
应用于 DNA 测序的离子电流测量新平台
- 批准号:
8514176 - 财政年份:2007
- 资助金额:
$ 162.13万 - 项目类别:
New Platform for Ionic Current Measurement with Application to DNA Sequencing
应用于 DNA 测序的离子电流测量新平台
- 批准号:
7685477 - 财政年份:2007
- 资助金额:
$ 162.13万 - 项目类别:
New Platform for Ionic Current Measurement with Application to DNA Sequencing
应用于 DNA 测序的离子电流测量新平台
- 批准号:
8711771 - 财政年份:2007
- 资助金额:
$ 162.13万 - 项目类别:
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