Candidate protein biomarker discovery by full automatic integration of Orbitrap full MS1 spectral peptide profiling and X!Tandem MS2 peptide sequencing is investigated by analyzing mass spectra from brain tumor sample...Candidate protein biomarker discovery by full automatic integration of Orbitrap full MS1 spectral peptide profiling and X!Tandem MS2 peptide sequencing is investigated by analyzing mass spectra from brain tumor samples using Peptrix. Potential protein candidate biomarkers found for angiogenesis are compared with those previously reported in the literature and obtained from previous Fourier transform ion cyclotron resonance （FT-ICR） peptide profiling. Lower mass accuracy of peptide masses measured by Orbitrap compared to those measured by FT-ICR is com- pensated by the larger number of detected masses separated by liquid chromatography （LC）, which can be directly linked to protein identifications. The number of peptide sequences divided by the number of unique sequences is 9248/6911 ~ 1.3. Peptide sequences appear 1.3 times redundant per up-regulated protein on average in the peptide profile matrix, and do not seem always up-reg- ulated due to tailing in LC retention time （40%）, modifications （40%） and mass determination errors （20%）. Significantly up-regulated proteins found by integration of X!Tandem are described in the literature as tumor markers and some are linked to angiogenesis. New potential biomarkers are found, but need to be validated independently. Eventually more proteins could be found by actively involving MS2 sequence information in the creation of the MS1 peptide profile matrix.展开更多
基金supported at the Erasmus Medical Center in Rotterdam by the Virgo Consortium(www.virgo.nl) and the EU P-mark project,and finished at the Academic Medical Center,University of Amsterdam
文摘Candidate protein biomarker discovery by full automatic integration of Orbitrap full MS1 spectral peptide profiling and X!Tandem MS2 peptide sequencing is investigated by analyzing mass spectra from brain tumor samples using Peptrix. Potential protein candidate biomarkers found for angiogenesis are compared with those previously reported in the literature and obtained from previous Fourier transform ion cyclotron resonance （FT-ICR） peptide profiling. Lower mass accuracy of peptide masses measured by Orbitrap compared to those measured by FT-ICR is com- pensated by the larger number of detected masses separated by liquid chromatography （LC）, which can be directly linked to protein identifications. The number of peptide sequences divided by the number of unique sequences is 9248/6911 ~ 1.3. Peptide sequences appear 1.3 times redundant per up-regulated protein on average in the peptide profile matrix, and do not seem always up-reg- ulated due to tailing in LC retention time （40%）, modifications （40%） and mass determination errors （20%）. Significantly up-regulated proteins found by integration of X!Tandem are described in the literature as tumor markers and some are linked to angiogenesis. New potential biomarkers are found, but need to be validated independently. Eventually more proteins could be found by actively involving MS2 sequence information in the creation of the MS1 peptide profile matrix.
