HUPO2011上 全球蛋白质组学研究者汇聚一堂推进人类蛋白质组计划
瑞士日内瓦,蛋白质组研究领域的领袖们在HUPO 2011上汇聚一堂,为人类蛋白质组计划(Human Proteome Project , HPP) 定义新的短期里程碑。这一全球范围内的聚会,旨在绘制今后五到十年全人类的蛋白质组蓝图。该计划将在HUPO上9月5日举行的AB SCIEX研讨会上启动,以HPP领导者Pierre Legrain的介绍开场。
什么是HPP?人类蛋白质组计划(Human Proteome Project,HPP)建立了全球蛋白质组学研究者的合作,HUPO组织发起的目标旨在归类和描绘出人体内的所有蛋白质。该计划有两大主要方向:基于染色体的HPP(cHPP),关注于对每个染色体蛋白的子集进行注释;另一个是生物疾病驱动的HPP(bdHPP),目标是回答和疾病相关的生物问题。为了识别、定量和注释所有的人类蛋白质编码基因,HPP将使用三种工具:质谱、亲和抗体、以及生物信息学。为每个方法,HPP都定义了指导原则,对实验步骤,样品处理和数据分析做了推荐。
最终的目标是:产生高质量的结果,届时全球的研究者们将可普遍获得这些结果。在长期的计划中,HPP的目标是,把蛋白质组学从研究带入临床的应用。
HPP项目是怎样开始的?
几年以前HPP项目就开始策划,但是实现项目目标所需的工具直至最近才变得可用。近年来质谱技术获得显著提高,尤其是其重现性、通量、分辨率、精度和分析质量方面。这些提高使得质谱具有足够的精度来检测和定量多样化的蛋白,即使是在痕量的浓度水平下。新的技术也使研究人员可比较从不同的组织和试验得到的数据库,来研究一个样品中蛋白存在和表达的水平,这些是HPP的核心元素。
例如,SWATH™采集技术,是瑞士苏黎世大学的Ruedi Aebersold和其同事们发明的,是第一个基于质谱的技术,可以同时定性和定量一个样品中所有的蛋白和多肽——只需一次分析——快速、准确、重现。AB SCIEX 的TripleTOF™5600 系统使SWATH采集方法的开发成为可能,它独一无二地集成了以下能力:超高速的采集、定量能力、准确质量、高分辨率。
主要的挑战是什么?
HPP项目的两大主要挑战将会是:说服足够大的研究实验室加入该集团,并确保进行足够的定量分析、从而发展非常大规模的数据库。在长期的计划中,HPP将面临第三种挑战:说服诊所使用质谱来诊断。
为实现HPP的目标,非常需要大型和有影响力的研究组。集团的每一个成员将被要求专注于一种疾病或生物问题上,遵循指导原则,接受开放的交叉分析,并在发表论文前分享他们的结果。
除了确保高质量和重现性的结果,集团需要优秀的定量工具来生成参考蛋白的蛋白库。这要求高灵敏的质谱仪,比如最近发展的TripleTOF 5600。
诊所传统上使用基于抗体的方法来诊断,这种技术有局限性,有时不能生成所需的结果。为了将来把人类蛋白质组学发现的结果应用到临床上,诊所将需要把原来的诊断方法转换为质谱法。
AB SCIEX的角色?
AB SCIEX,生命科学分析领域的全球领导者,是HPP工业咨询委员会的成员,并赞助了HUPO会议的系列研讨会。
HPP研讨会之后,两个进一步的研讨会将侧重于多肽定量方面的新型质谱技术和工作流,包括SWATH采集法。该研讨会向所有HOPO 2011的参会代表开放,会上的报告将来自全球的蛋白质组学研究领袖们、以及HUPO组织方和ABSCIEX公司。9月3-7日,HUPO 2011在瑞士日内瓦召开。
在质谱技术最新的进展方面,AB SCIEX已做出了卓越的贡献,这些贡献将使HPP研究受益,AB SCIEX提供了全面的质谱系列:TripleTOF™, QTRAP®, 三重四极杆、和TOF/TOF™ 系统,以及先进的软件,和突破性的SelexION™ 技术。
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参考英文原文:
Leading proteomics researchers are gathering at the HUPO 2011 meeting in Geneva, Switzerland, to define new short-term milestones for the Human Proteome Project (HPP). This global collaboration aims to map the entire human proteome over the next five to ten years. The project will be introduced to HUPO delegates at an AB SCIEX workshop on 5th September, opening with an introduction by the HPP leader, Pierre Legrain.
What is the HPP?
The Human Proteome Project is a global collaboration between proteomics researchers, a HUPO initiative that aims to assign and characterise all proteins in the human body. The project has two main directions: chromosome-based HPP (cHPP), focusing on annotating subsets of proteins for each chromosome, and biology disease-driven HPP (bdHPP), aiming to answer biological and disease-related questions. To identify, quantify and annotate all human protein-coding genes, the HPP will use three tools: mass spectrometry, antibody affinity and bioinformatics. For each method the HPP is defining guidelines with recommendations for experimental procedures, sample handling and data analysis.
The ultimate goal is to produce high-quality results that would be universally available to researchers all over the world. In the long term, the HPP aims to take proteomics beyond research and into clinical applications.
Why is the project starting now?
Planning for the HPP began several years ago, but the tools that will be needed to achieve the project’s goals have only recently become available. Mass spectrometry technologies have significantly improved in recent years, particularly in terms of reproducibility, throughput, resolution, and accuracy and quality of the analysis. These improvements should allow sufficient accuracy for detecting and quantifying diverse proteins, even at low level of concentration. New technologies also make it possible to compare databases from different tissues and experiments to study the presence and level of expression of proteins in a sample, which is a key element of the HPP.
For example, the SWATH™ Acquisition technique, which was developed in collaboration with Prof Ruedi Aebersold and his colleagues at the ETH Zürich, is the first mass spectrometry-based technique that allows simultaneous quantitative and qualitative detection of all proteins and peptides in a sample - from a single analysis - in a fast, accurate, and reproducible manner. The development of SWATH Acquisition was made possible with the superior capabilities of the AB SCIEX TripleTOF™ 5600 System, which combines ultra-high acquisition speed with quantitative capabilities, accurate mass and high resolution.
What will be the main challenges?
The two main challenges for the HPP will be to convince enough large research laboratories to join the consortium, and to ensure sufficient quantitation to develop such large-scale databases. In the long term, the HPP will face a third challenge in convincing clinics to use mass spectrometry for diagnosis.
In order to achieve the HPP’s goals, large and influential proteomics research groups will be needed. Each member of the consortium will be asked to focus on one disease or biological question, to follow the guidelines and to accept open cross-analysis and sharing of their results before publishing.
In addition to ensuring high quality and reproducibility of the results, the consortium needs excellent quantitation to produce protein libraries of reference proteins. This requires sensitive high-power mass spectrometers, such as the recently developed TripleTOF 5600.
Clinics traditionally use antibody- based methods for diagnostics, a limited technique that sometimes cannot produce the required results. In order to apply human proteomics discovery to clinical use in the future, clinics will need to convert to mass spectrometry-based approaches.
What is AB SCIEX’s role?
AB SCIEX, a global leader in life science analytical technologies, is a member of the HPP’s Industry Advisory Board and is sponsoring a series of workshops at HUPO.
The HPP workshop will be followed by two further workshops focusing on new mass spectrometry technologies and workflows in peptide quantitation, including SWATH Acquisition. The workshops are open to all HUPO 2011 delegates, and will consist of talks from leading proteomics researchers from around the world, as well as from HUPO and AB SCIEX. HUPO 2011 takes place from 3-7 September, in Geneva, Switzerland.
AB SCIEX has contributed significantly to recent advances in mass spectrometry technology that could greatly benefit the HPP research, and offers a complete range of TripleTOF™, QTRAP®, Triple Quad™ and TOF/TOF™ Systems, as well as advanced software and the ground-breaking SelexION™ Technology.
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