QuickMod: A Tool for Open Modification Spectrum Library Searches

Abstract

MS2 library spectra are rich in reproducible information about peptide fragmentation patterns compared to theoretical spectra modeled by a sequence search tool. So far, spectrum library searches are mostly applied to detect peptides as they are present in the library. However, they also allow finding modified variants of the library peptides if the search is done with a large precursor mass window and an adapted Spectrum-Spectrum Match (SSM) scoring algorithm. We perform a thorough evaluation on the use of library spectra as opposed to theoretical peptide spectra for the identification of PTMs, analyzing spectra of a well-annotated modification-rich test data set compiled from public data repositories. These initial studies motivate the development of our modification tolerant spectrum library search tool QuickMod, designed to identify modified variants of the peptides listed in the spectrum library without any prior input from the user estimating the modifications present in the sample. We built the search algorithm of QuickMod after carefully testing different SSM similarity scores. The final spectrum scoring scheme uses a support vector machine (SVM) on a selection of scoring features to classify correct and incorrect SSM. After identification of a list of modified peptides at a given False Discovery Rate (FDR), the modifications need to be positioned on the peptide sequence. We present a rapid modification site assignment algorithm and evaluate its positioning accuracy. Finally, we demonstrate that QuickMod performs favorably in terms of speed and identification rate when compared to other software solutions for PTM analysis.

pFind–Alioth: A novel unrestricted database search algorithm to improve the interpretation of high-resolution MS/MS data

“…The spectral network approach proposed by Bandeira et al takes advantage of modified and unmodified peptide pairs to reduce noise peaks and hence improves the efficiency of peptide identification [25,26]. Spectral library searching algorithms, such as pMatch [27] and QuickMod [28], are also based on finding spectrum pairs with mass shifts that can be interpreted as unknown modifications.…”

MzJava: An open source library for mass spectrometry data processing

“…The Java Proteomics Library (JPL, javaprotlib.sourceforge.net) provides an API to process MS/MS spectra and their annotation. It served as the code base for several software projects dealing with MS/MS searches [13], spectral libraries and open modification searches [14], and data-independent quantification [15]. The PRIDE tool suite (http://pride-toolsuite.googlecode.com) contains a set of pure Java libraries, tools and packages designed to process and visualize versatile MS proteomics data [3].…”

Spectral matching approaches in hyperspectral image processing

“…The application of the de-noising techniques might eliminate the useful absorption peaks. Spectral library search tools such as QuickMod employ spectrum-spectrum matching and scoring algorithms, where a weight is given to the intensities of matching and nonmatching peaks (Ahrne et al 2011). The small informative peaks and overlapped peaks in the spectra cannot be easily identified by the software and hence the shape of the peak cannot be described accurately.…”

“…This results in labelling same species as different classes. Modification-tolerant tools are being developed where, even if part of the target spectrum is found, the result might be a number of partially matched hits (Li et al 2004;Ahrne et al 2011). Such instances of spectral matching with environmentally modified spectra were reported during an oil spill analysis (Salem, El-Ghazawi, and International Journal of Remote Sensing 8235 Kafatos 2001;Li et al 2004), and during quality control of herbal medicines (Chau et al 2001).…”