Software for automated interpretation of heparan sulfate tandem mass spectra

用于自动解释硫酸乙酰肝素串联质谱的软件

基本信息

  • 批准号:
    8984998
  • 负责人:
  • 金额:
    $ 32.97万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2015
  • 资助国家:
    美国
  • 起止时间:
    2015-09-15 至 2017-06-30
  • 项目状态:
    已结题

项目摘要

 DESCRIPTION (provided by applicant): Software for automated interpretation of heparan sulfate tandem mass spectra the expression of heparan sulfate (HS) is required for embryonic development and the functioning of every physiological system. Present in intracellular granules, on cell surfaces and in extracellular matrices, HS binds to growth factor families and their receptors. These binding interactions serve to modulate cellular responses to growth factor stimuli in a cell-type and developmental state specific manner. The challenge to exploitation of HS structures as drugs lies in the nature of their biosynthesis and in their chemical properties. HS chains are assembled in the endoplasmic reticulum and Golgi apparatus by a series of enzymes acting in a non-template driven manner. Chains are first polymerized and then subject to modification events that produce mature chains with a regulated domain structure overlaid by substantial heterogeneity. As the HS chain biosynthesis proceeds, the number of biosynthetic enzymatic isoforms increases. These enzymes, including 6O- sulfotransferases and 3O-sulfotransferases, are expressed in a tissue and cell-type specific manner and are believed to modify substrates with isoform specificity. The result is HS chains that have phenotype-specific structure and protein binding functions. Despite the availability of mouse mutants for many of the biosynthetic enzymes, progress in HS biomedicine has suffered from the lack of widely adopted sequencing methods. Over the past few years, however, electron activated dissociation methods (ExD) have been developed in mass spectrometry laboratories. These methods, including electron detachment dissociation (EDD) and negative electron detachment dissociation (NETD) demonstrate feasibility of instrumental sequencing of HS saccharides. The advantage to these methods is that they require no or minimal derivatization, are compatible with high throughput, and provide rich structural information of the HS saccharides. The tandem mass spectra are highly complex, however, and tailor-made bioinformatics methods are necessary to convert raw data into sequences. We have demonstrated feasibility of an algorithm (HS-SEQ) for sequencing HS saccharide from ExD tandem mass spectra. We now propose to develop HS-SEQ so that it can provide better performance and full features supporting automated HS analysis, and be easily used by the wider biomedical community. The availability of mass spectrometers with NETD or EDD capability will grow rapidly over the next few years. We will develop a pipeline for data processing that includes all steps necessary to go from raw data to sequence information. This pipeline will be designed for use by biomedical scientists familiar with HS biochemistry and/or proteomics methods. The HS- SEQ pipeline will run as a web service and be available in source code and binary installer form under a Creative Commons license
 描述(由申请人提供):硫酸乙酰肝素串联质谱自动判读软件,硫酸乙酰肝素(HS)的表达是胚胎发育和每个生理系统功能所必需的。HS存在于细胞内颗粒、细胞表面和细胞外基质中,与生长因子家族及其受体结合。这些结合相互作用用于以细胞类型和发育状态特异性方式调节对生长因子刺激的细胞应答。利用HS结构作为药物的挑战在于它们的生物合成的性质和它们的化学性质。HS链在内质网和高尔基体中通过一系列以非模板驱动方式作用的酶组装。链首先聚合,然后经历修饰事件,产生具有被大量异质性覆盖的调节结构域结构的成熟链。随着HS链生物合成的进行,生物合成酶同工型的数量增加。这些酶,包括6 O-磺基转移酶和3 O-磺基转移酶,以组织和细胞类型特异性方式表达,并被认为以同种型特异性修饰底物。结果是HS链具有表型特异性结构和蛋白质结合功能。尽管许多生物合成酶的小鼠突变体的可用性,HS生物医学的进展受到缺乏广泛采用的测序方法的影响。然而,在过去的几年中,电子活化解离方法(ExD)已在质谱实验室中开发。这些方法,包括电子分离解离(EDD)和负电子分离解离(NETD),证明了仪器测序的可行性。这些方法的优点是它们不需要衍生化或需要最少的衍生化,与高通量相容,并提供HS的丰富结构信息。然而,串联质谱非常复杂,需要定制的生物信息学方法将原始数据转换为序列。我们已经证明了从ExD串联质谱中测序HS糖的算法(HS-SEQ)的可行性。我们现在建议开发HS-SEQ,以便它可以提供更好的性能和支持自动化HS分析的完整功能,并易于被更广泛的生物医学界使用。具有NETD或EDD功能的质谱仪的可用性将在未来几年内迅速增长。我们将开发一个数据处理管道,包括从原始数据到序列信息的所有必要步骤。这条管道将被设计用于熟悉HS生物化学和/或蛋白质组学方法的生物医学科学家。HS-SEQ管道将作为Web服务运行,并在Creative Commons许可下以源代码和二进制安装程序的形式提供

项目成果

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JOSEPH ZAIA其他文献

JOSEPH ZAIA的其他文献

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{{ truncateString('JOSEPH ZAIA', 18)}}的其他基金

Methods for measuring matrisome molecule similarity during disease processes
测量疾病过程中基质体分子相似性的方法
  • 批准号:
    10582128
  • 财政年份:
    2022
  • 资助金额:
    $ 32.97万
  • 项目类别:
Methods for measuring matrisome molecule similarity during disease processes
测量疾病过程中基质体分子相似性的方法
  • 批准号:
    10580774
  • 财政年份:
    2022
  • 资助金额:
    $ 32.97万
  • 项目类别:
Methods for measuring matrisome molecule similarity during disease processes
测量疾病过程中基质体分子相似性的方法
  • 批准号:
    10330789
  • 财政年份:
    2022
  • 资助金额:
    $ 32.97万
  • 项目类别:
Methods for determination of glycoprotein glycosylation similarities among disease states
确定疾病状态之间糖蛋白糖基化相似性的方法
  • 批准号:
    10194553
  • 财政年份:
    2019
  • 资助金额:
    $ 32.97万
  • 项目类别:
An open-source software suite for processing glycomics and glycoproteomics mass spectral data
用于处理糖组学和糖蛋白质组学质谱数据的开源软件套件
  • 批准号:
    9391486
  • 财政年份:
    2017
  • 资助金额:
    $ 32.97万
  • 项目类别:
A Thermo-Fisher Scientific Q-Exactive HF Mass Spectrometry System
Thermo-Fisher Scientific Q-Exactive HF 质谱系统
  • 批准号:
    9075665
  • 财政年份:
    2016
  • 资助金额:
    $ 32.97万
  • 项目类别:
Software for automated interpretation of heparan sulfate tandem mass spectra
用于自动解释硫酸乙酰肝素串联质谱的软件
  • 批准号:
    9337106
  • 财政年份:
    2015
  • 资助金额:
    $ 32.97万
  • 项目类别:
Software for automated interpretation of heparan sulfate tandem mass spectra
用于自动解释硫酸乙酰肝素串联质谱的软件
  • 批准号:
    9144851
  • 财政年份:
    2015
  • 资助金额:
    $ 32.97万
  • 项目类别:
Quantitative profiling of glycosaminoglycans from breast tumor tissue arrays
乳腺肿瘤组织阵列中糖胺聚糖的定量分析
  • 批准号:
    9079438
  • 财政年份:
    2014
  • 资助金额:
    $ 32.97万
  • 项目类别:
Quantitative profiling of glycosaminoglycans from breast tumor tissue arrays
乳腺肿瘤组织阵列中糖胺聚糖的定量分析
  • 批准号:
    8889224
  • 财政年份:
    2014
  • 资助金额:
    $ 32.97万
  • 项目类别:

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