De novo peptide sequencing and identification with precision mass spectrometry

De novo peptide sequencing and identification with precision mass spectrometry
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DOI:
10.1021/pr060271u
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发表时间:
2007-01-05
影响因子:
4.4
通讯作者:
Pevzner, Pavel A.
Pevzner, Pavel A.
中科院分区:
生物学2区
文献类型:
--
作者:
Frank, Ari M.;Savitski, Mikhail M.;Pevzner, Pavel A.

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最近,傅立叶变换、QTOF和Orbitrap等新型质谱计的出现标志着向精密质谱学时代的过渡,与低精度离子陷阱探测器相比,质量分辨率提高了2个数量级。我们研究了用精密质谱仪进行的多肽从头测序,并探索了与低精度数据分析相比的一些差异。我们展示了精确质谱学从头测序性能的显著提高如何为基于直接序列查找而不是将光谱与数据库进行比较的新的肽鉴定方法铺平了道路。通过直接序列查找,不仅可以非常高效地搜索数据库,而且可以以新的方式使用数据库,例如搜索癌症中的选择性剪接产物或融合蛋白的产物。我们的从头测序软件可从http://peptide.ucsd.edu/.下载
The recent proliferation of novel mass spectrometers such as Fourier transform, QTOF, and OrbiTrap marks a transition into the era of precision mass spectrometry, providing a 2 orders of magnitude boost to the mass resolution, as compared to low-precision ion-trap detectors. We investigate peptide de novo sequencing by precision mass spectrometry and explore some of the differences when compared to analysis of low-precision data. We demonstrate how the dramatically improved performance of de novo sequencing with precision mass spectrometry paves the way for novel approaches to peptide identification that are based on direct sequence lookups, rather than comparisons of spectra to a database. With the direct sequence lookup, it is not only possible to search a database very efficiently, but also to use the database in novel ways, such as searching for products of alternative splicing or products of fusion proteins in cancer. Our de novo sequencing software is available for download at http://peptide.ucsd.edu/.