High-Throughput De Novo Glycan Sequencing
高通量从头聚糖测序
基本信息
- 批准号:10000171
- 负责人:
- 金额:$ 44.73万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-09-01 至 2023-08-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAdoptedAlgorithm DesignAlgorithmsAnabolismAutoimmune DiseasesBehaviorBindingBioinformaticsBiologicalBiological MarkersBiomedical ResearchBiopolymersCarbonCardiovascular DiseasesCell AdhesionCommunitiesComplexComplex MixturesComputer softwareCouplingDataData SetDatabasesDevelopmentDiseaseDissociationEffectivenessElectron TransportEmbryonic DevelopmentEpitopesFourier transform ion cyclotron resonanceGenomeGlycoconjugatesGlycosidesHealthHigh Pressure Liquid ChromatographyImmune responseImpairmentIndividualIsomerismLinkLiquid ChromatographyLiquid substanceLung diseasesMachine LearningMalignant NeoplasmsMass Spectrum AnalysisMetabolicMethodsNatural graphiteNaturePathologic ProcessesPathway interactionsPatternPhasePhysiologicalPhysiological ProcessesPhysiologyPlayPolysaccharidesResearchResearch Project GrantsRoleSamplingSchemeSourceSpecificitySpeedStructureStructure-Activity RelationshipSurfaceVacuumVariantanalytical methodbasebioinformatics toolcatalystcell growthdesigngenetic linkage analysisglycosylationimprovedinstrumentmass spectrometernervous system disordernovelpathogenperformance testsprogramsprotein foldingreconstructiontandem mass spectrometrytherapeutic targettoolultraviolet
项目摘要
Glycosylation fulfills important physiological functions, including protein folding, embryogenesis, cell adhesion,
pathogen recognition, and immune response. The multifaceted roles glycosylation plays derive from the
presence of a range of glycan epitopes, where a small structural variation can have a profound impact on
functions. Further, a glycome consists of many closely related structures, with their relative amounts determined
by metabolic conditions in a cell- and growth-specific manner. Altered glycosylation is linked to many diseases,
including cardiovascular, pulmonary, neurological and autoimmune disorders, and cancer. Thus, there is a clear
need for analytical methods that can rapidly identify and quantify the many glycoforms in a glycome from different
health and disease states. Finally, no genome-predicted glycan database exists due to the unscripted nature of
glycan biosynthesis, and discovery of new glycan structures must be achieved by de novo methods.
Although tandem mass spectrometry-based biopolymer sequencing has been the major catalyst to the recent
rapid advance of 'omics, the prevailing collisionally activated dissociation method often fails to provide sufficient
glycan structural detail at the MS2 level, whereas the MSn approach lacks the speed, sensitivity, and quantitative
potential for high-throughput glycome analysis. We have recently developed an electronic excitation dissociation
(EED) method that can yield rich structural information in a single stage of MS/MS analysis. However, the impact
of EED on glycomics research is currently limited by its poor accessibility, insufficient coupling to on-line glycan
separation methods, and difficulty in interpretation of complex glycan EED tandem mass spectra.
Here, we propose to develop an integrated approach that combines EED with on-line liquid chromatography (LC)
separation and a novel bioinformatics tool to achieve high-throughput, de novo, and comprehensive glycome
characterization. We will explore the potential of EED for analysis of glycans in various derivatized forms, study
their fragmentation behaviors, and establish fragmentation rules for the development of bioinformatics software.
We will optimize conditions for efficient coupling of EED to reversed-phase, and porous graphitic carbon LC, and
develop an LC-EED-MS/MS approach for simultaneous characterization and quantitation of glycan mixtures. We
will implement EED on a Q-TOF instrument to improve its access to the glycoscience community. Finally, we will
develop and rigorously test the performance of a novel bioinformatics software that can rapidly and accurately
determine each glycan's structure from its tandem MS spectra. The proposed algorithm is fundamentally different
from most existing software, in that it no longer relies solely on glycosidic and cross-ring fragments for topology
and linkage analysis, but rather adopts a machine learning approach that considers the contexts of various types
of fragment peaks, and the spectral features associated with different linkage configurations and structural
motifs. The availability of such a high-throughput, de novo glycan sequencing tool will have an immense impact
on many biomedical research fields, as glycosylation plays critical roles in almost all biological pathways.
糖基化完成了重要的生理功能,包括蛋白质折叠、胚胎发生、细胞粘附、
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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Pengyu Hong其他文献
Pengyu Hong的其他文献
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{{ truncateString('Pengyu Hong', 18)}}的其他基金
Identifying and addressing missingness and bias to enhance discovery from multimodal health data
识别和解决缺失和偏见,以增强多模式健康数据的发现
- 批准号:
10637391 - 财政年份:2023
- 资助金额:
$ 44.73万 - 项目类别:
Intelligent Interfaces for Interactive Analysis of High-Content Cellular Images
用于高内容细胞图像交互式分析的智能界面
- 批准号:
7470047 - 财政年份:2007
- 资助金额:
$ 44.73万 - 项目类别:
Intelligent Interfaces for Interactive Analysis of High-Content Cellular Images
用于高内容细胞图像交互式分析的智能界面
- 批准号:
7316890 - 财政年份:2007
- 资助金额:
$ 44.73万 - 项目类别:
Intelligent Interfaces for Interactive Analysis of High-Content Cellular Images
用于高内容细胞图像交互式分析的智能界面
- 批准号:
7617093 - 财政年份:2007
- 资助金额:
$ 44.73万 - 项目类别:
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