PRIDE Converter - Efficient Database Deposition of Mass Spectrometry Data

在分子生物学的快速发展中，生物数据的公开是至关重要的。然而，令人遗憾的是，与基因组学和转录组学等其他学科相比，公共领域存储库中的蛋白质组学数据量仍然相当低。蛋白质组学数据最著名的公共存储库之一是剑桥大学EBI的蛋白质组学鉴定数据库（PRIDE, http://www.ebi.ac.uk）。目前，蛋白质组学期刊越来越多地要求将MS数据公开存储到公共存储库，特别是到PRIDE，以支持相关手稿的发表。与此同时，资助机构（如英国的BBRSR和Wellcome Trust）显然支持这一趋势，认为这是使所提供资金价值最大化的一种方式。然而，在实践中，如果没有可靠的和“用户友好的”提交工具，能够有效地捕获技术和生物元数据，这个公共数据共享政策就不能成功提供给研究界。提交工具PRIDE Converter （http://code.google.com/p/pride-converter）就是带着这个想法开发的。它是一个开源的、独立于平台的软件，它的成功很大程度上归功于它易于使用的图形用户界面（GUI）组件。PRIDE转换器是目前最全面和最流行的这种工具，因为它使提交MS数据更容易和更直接的过程。在过去两年中，它无疑是PRIDE数据内容大幅增长的关键因素，并已成为大多数研究人员事实上的PRIDE提交工具。从2009年1月到2010年9月，PRIDE通过PRIDE转换器接收了243份数据沉积，包括6360多万份质谱。这里提出的再开发是基于PRIDE策展人与数据存款人直接交换收集到的用户反馈，以及与期刊编辑的讨论，以及质谱（MS）社区标准的最新发展。除了技术目标a-b（见“技术摘要”），我们迫切需要实现对当前社区数据标准的支持。用于表示质谱的mzML是最近发布的，它取代了目前由PRIDE Converter支持的mzData。用于表示蛋白质和肽鉴定的mzIdentML最近已经发布，并且已经得到Mascot 2.3和其他工具的支持。本提案的关键目标c)是在PRIDE转换器中实现完整的mzML/mzIdentML支持。除了数据表示标准之外，HUPO蛋白质组学标准倡议还发布了一系列“最低要求”文档，描述了蛋白质组学实验应报告的元数据项目。目前，对这些最低要求文档的遵守并没有得到PRIDE Converter的验证。关键目标d)是实现这样的验证，但也要通过为重复提交过程提供模板机制来有效地遵守这些需求。这将使数据的重用更加可行，并允许对数据进行更可靠的全局重新分析（荟萃分析研究）。在目前的形式下，PRIDE转换器只能为定量质谱技术提供基本的支持，而定量质谱技术正迅速成为标准的蛋白质组学方法。关键目标e)旨在实现轻量级的PRIDE转换器支持定量蛋白质组学工具。最终目标f)是蛋白质推断的标准化。目前，蛋白质组学搜索工具通常从一系列等效的蛋白质选择中选择一个给定的肽集。我们将尽可能在不同的搜索工具之间标准化这一过程，以确保蛋白质组学数据的最佳可比性。

Public availability of biological data has been of paramount importance in the rapid development of molecular biology. However, the amount of proteomics data in public domain repositories is regrettably still quite low in comparison with other disciplines like genomics and transcriptomics. One of the most prominent public repositories for proteomics data is the PRoteomics IDEntifications database (PRIDE, http://www.ebi.ac.uk) at the EBI, in Cambridge. At present proteomics journals are increasingly mandating public deposition of MS data to public repositories in general, and to PRIDE in particular, to support the publication of related manuscripts. At the same time, funding agencies (such as BBRSR and the Wellcome Trust in the UK) are clearly supporting this trend as a way to maximize the value of the funds provided. However, in practical terms, this public data-sharing policy cannot succeed if no reliable and 'user-friendly' submission tools, that can efficiently capture the technical and biological metadata, are provided to the research community. The submission tool PRIDE Converter (http://code.google.com/p/pride-converter) was developed with that idea in mind. It is an open source, platform independent software and a big part of its success can be attributed to its easy-to-use graphical user interface (GUI) component. PRIDE Converter is currently by far the most comprehensive and popular tool of this kind, since it made the submission of MS data a much easier and more straightforward process. It has definitely been the key factor in the huge growth in data contents in PRIDE for the last two years and has become the de facto submission tool for PRIDE for most researchers. From Jan 2009 to Sept 2010, PRIDE has received 243 data depositions, comprising more than 63.6 million mass spectra, through PRIDE Converter. The redevelopment proposed here is based on user feedback gathered by PRIDE curators in direct exchange with data depositors, as well as on discussions with journal editors, and recent development of community standards for mass spectrometry (MS). Beyond the technical objectives a-b (see 'Technical Summary'), we urgently need to implement support for current community data standards. mzML for the representation of mass spectra has recently been published and supersedes mzData, currently supported by PRIDE Converter. mzIdentML for the representation of protein and peptide identifications has recently been released and is already supported by Mascot 2.3 and other tools. Key objective c) of this proposal is to implement full mzML/mzIdentML support in PRIDE Converter. In addition to standards for data representation, the HUPO Proteomics Standards Initiative has published a series of 'Minimum Requirements' documents, describing the metadata items which should be reported for proteomics experiments. Currently, adherence to these Minimum requirements documents is not validated by the PRIDE Converter. Key objective d) is to implement such validation, but also to make adherence to these requirements efficient by providing a template mechanism for repetitive submission processes. This will make the reuse of the data more feasible and will allow perform more reliable global re-analysis of data (meta-analysis studies). In its current form, the PRIDE Converter provides only rudimentary support for quantitative MS technologies, which are quickly becoming the standard proteomics approach. Key objective e) aims to implement light weight PRIDE Converter support for quantitative proteomics tools. The final objective f) is the standardisation of protein inference. Currently, proteomics search tools usually select one of a range of equivalent protein choices for a given peptide set. We will standardise this process as much as possible between different search tools, to ensure optimised comparability of proteomics data.