ABSTRACT
The large-scale identification, characterization and quantification of proteins in biological samples by liquid chromatography-mass spectrometry (LC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/ MS)-based proteomic methods play a crucial role in biomedical research [1,2]. For example, in biomarker discovery studies, a common aim is to elucidate a set of proteins that can be used to reliably differentiate diseased and normal samples by abundance measurements. Precision and accuracy are critical for confident protein biomarker discovery and validation. In "bottom-up" approaches, proteins are cleaved by sequence-specific proteases such as trypsin prior to analysis. A protein fold change can be inferred from the relative abundance of peptides across samples, where peptide identification and quantification can be accomplished in separate steps [3]. In this paper, we consider the problem of relative isotopic quantification
of peptides in LC-MS based on time-of-flight (TOF) instruments. It is assumed herein that a list of candidate peptides has been compiled a priori, and that we are interested in measuring the relative abundance of their isotopes (natural or labeled).
