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bioRxiv · 10.1101/2023.05.02.539167

Analysis of tandem mass spectrometry data with CONGA: Combining Open and Narrow searches with Group-wise Analysis

Freestone, J. A.·Noble, W. S.·Keich, U.
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Abstract

Searching tandem mass spectrometry proteomics data against a database is a well-established method for assigning peptide sequences to observed spectra but typically cannot identify peptides harboring unexpected post-translational modifications (PTMs). Open modification searching aims to address this problem by allowing a spectrum to match a peptide even if the spectrums precursor mass differs from the peptide mass. However, expanding the search space in this way can lead to a loss in statistical power to detect peptides. We therefore developed a method, called CONGA, that takes into account results from both types of searches--a traditional "narrow window" search and an open modification search--while carrying out rigorous false discovery rate (FDR) control. The result is an algorithm that provides the best of both worlds: the ability to detect unexpected PTMs without a concomitant loss of power to detect unmodified peptides.

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Freestone, J. A., Noble, W. S., Keich, U.. 2023-05-03. Analysis of tandem mass spectrometry data with CONGA: Combining Open and Narrow searches with Group-wise Analysis. https://doi.org/10.1101/2023.05.02.539167

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