Enhancement of sensitivity and resolution of surface-enhanced, laser desorption/lonization time-of-flight mass spectrometric records for serum peptides using time-series analysis techniques
Enhancement of sensitivity and resolution of surface-enhanced, laser desorption/lonization time-of-flight mass spectrometric records for serum peptides using time-series analysis techniques
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DOI：
10.1373/clinchem.2004.037283
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发表时间：
2005-01-01
影响因子：
9.3
通讯作者：
Manos, DM
中科院分区：
文献类型：
--
作者：
Malyarenko, DI;Cooke, WE;Manos, DM
背景资料：用于生物标志物发现的生物样品中的肽/蛋白质浓度的测量通常使用具有表面处理程序的高灵敏度质谱仪来浓缩重要的肽。这些飞行时间（TOF）仪器通常具有低质量分辨率和与其检测器相关联的相当大的电子噪声。最终结果是峰的不必要重叠、明显的质量抖动以及难以将质量峰与背景噪声区分开。方法：在PBS II仪器上从空白、疏水和IMAC-Cu ProteinChip（R）阵列（Ciphergen Biosystems，Inc.）与校准肽混合物或合并的血清孵育。在不同位置的单次和多次激光照射后记录TOF数据。相关分析用于时间序列校正。在基线去除和噪声重标度后，使用目标滤波器抑制噪声并提高分辨率。结果：所开发的算法补偿了归因于检测器过载的电子噪声，去除了由电荷积累引起的基线，检测并校正了质量峰抖动，增强了更高质量的信号幅度，并通过使用反卷积滤波器提高了分辨率。当在任何峰识别程序之前应用于SELDI-TOF数据时，这些时间序列技术可以改进数据以使峰识别过程更简单且更鲁棒。这些改进可适用于使用模拟（而非计数）检测器的大多数TOF仪器。(C)2005年美国临床化学协会。
Background: Measurement of peptide/protein concentrations in biological samples for biomarker discovery commonly uses high-sensitivity mass spectrometers with a surf ace-processing procedure to concentrate the important peptides. These time-of-flight (TOF) instruments typically have low mass resolution and considerable electronic noise associated with their detectors. The net result is unnecessary overlapping of peaks, apparent mass jitter, and difficulty in distinguishing mass peaks from background noise. Many of these effects can be reduced by processing the signal using standard timeseries background subtraction, calibration, and filtering techniques.Methods: Surface-enhanced laser desorption/ionization (SELDI) spectra were acquired on a PBS II instrument from blank, hydrophobic, and IMAC-Cu ProteinChip((R)) arrays (Ciphergen Biosystems, Inc.) incubated with calibration peptide mixtures or pooled serum. TOF data were recorded after single and multiple laser shots at different positions. Correlative analysis was used for time-series calibration. Target filters were used to suppress noise and enhance resolution after baseline removal and noise rescaling.Results: The developed algorithms compensated for the electronic noise attributable to detector overload, removed the baseline caused by charge accumulation, detected and corrected mass peak jitter, enhanced signal amplitude at higher masses, and improved the resolution by using a deconvolution filter.Conclusions: These time-series techniques, when applied to SELDI-TOF data before any peak identification procedure, can improve the data to make the peak identification process simpler and more robust. These improvements may be applicable to most TOF instrumentation that uses analog (rather than counting) detectors. (C) 2005 American Association for Clinical Chemistry.