Research output: Contribution to journal › Article › peer-review
De Novo protein sequencing by combining top-down and bottom-up tandem mass spectra. / Liu, Xiaowen; Dekker, Lennard J.M.; Wu, Si; Vanduijn, Martijn M.; Luider, Theo M.; Tolić, Nikola; Kou, Qiang; Dvorkin, Mikhail; Alexandrova, Sonya; Vyatkina, Kira; Paša-Tolić, Ljiljana; Pevzner, Pavel A.
In: Journal of Proteome Research, Vol. 13, No. 7, 03.07.2014, p. 3241-3248.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - De Novo protein sequencing by combining top-down and bottom-up tandem mass spectra
AU - Liu, Xiaowen
AU - Dekker, Lennard J.M.
AU - Wu, Si
AU - Vanduijn, Martijn M.
AU - Luider, Theo M.
AU - Tolić, Nikola
AU - Kou, Qiang
AU - Dvorkin, Mikhail
AU - Alexandrova, Sonya
AU - Vyatkina, Kira
AU - Paša-Tolić, Ljiljana
AU - Pevzner, Pavel A.
PY - 2014/7/3
Y1 - 2014/7/3
N2 - There are two approaches for de novo protein sequencing: Edman degradation and mass spectrometry (MS). Existing MS-based methods characterize a novel protein by assembling tandem mass spectra of overlapping peptides generated from multiple proteolytic digestions of the protein. Because each tandem mass spectrum covers only a short peptide of the target protein, the key to high coverage protein sequencing is to find spectral pairs from overlapping peptides in order to assemble tandem mass spectra to long ones. However, overlapping regions of peptides may be too short to be confidently identified. High-resolution mass spectrometers have become accessible to many laboratories. These mass spectrometers are capable of analyzing molecules of large mass values, boosting the development of top-down MS. Top-down tandem mass spectra cover whole proteins. However, top-down tandem mass spectra, even combined, rarely provide full ion fragmentation coverage of a protein. We propose an algorithm, TBNovo, for de novo protein sequencing by combining top-down and bottom-up MS. In TBNovo, a top-down tandem mass spectrum is utilized as a scaffold, and bottom-up tandem mass spectra are aligned to the scaffold to increase sequence coverage. Experiments on data sets of two proteins showed that TBNovo achieved high sequence coverage and high sequence accuracy.
AB - There are two approaches for de novo protein sequencing: Edman degradation and mass spectrometry (MS). Existing MS-based methods characterize a novel protein by assembling tandem mass spectra of overlapping peptides generated from multiple proteolytic digestions of the protein. Because each tandem mass spectrum covers only a short peptide of the target protein, the key to high coverage protein sequencing is to find spectral pairs from overlapping peptides in order to assemble tandem mass spectra to long ones. However, overlapping regions of peptides may be too short to be confidently identified. High-resolution mass spectrometers have become accessible to many laboratories. These mass spectrometers are capable of analyzing molecules of large mass values, boosting the development of top-down MS. Top-down tandem mass spectra cover whole proteins. However, top-down tandem mass spectra, even combined, rarely provide full ion fragmentation coverage of a protein. We propose an algorithm, TBNovo, for de novo protein sequencing by combining top-down and bottom-up MS. In TBNovo, a top-down tandem mass spectrum is utilized as a scaffold, and bottom-up tandem mass spectra are aligned to the scaffold to increase sequence coverage. Experiments on data sets of two proteins showed that TBNovo achieved high sequence coverage and high sequence accuracy.
UR - http://www.scopus.com/inward/record.url?scp=84903691273&partnerID=8YFLogxK
U2 - 10.1021/pr401300m
DO - 10.1021/pr401300m
M3 - Article
C2 - 24874765
AN - SCOPUS:84903691273
VL - 13
SP - 3241
EP - 3248
JO - Journal of Proteome Research
JF - Journal of Proteome Research
SN - 1535-3893
IS - 7
ER -
ID: 100631086