Cross-Linking Mass Spectrometry Data Analysis

In this chapter, we will review mass spectrometry-based proteomics and focus on the development of data analysis methods in chemical cross-linking combined with mass spectrometry (CL-MS). CL-MS is one remarkable technology in proteomics that can help decipher three-dimensional structures of proteins and reveal the detail of protein-protein interactions (PPIs) in a high-throughput manner. We will organize this chapter as follows: Section 1 briefly introduces the working flow of CL-MS with illustrative figures. Section 2 reviews non-cleavable cross-linking search methods. Section 3 reviews cleavable cross-linking search methods. Section 4 compares non-cleavable cross-linking search methods with cleavable cross-linking search methods. Section 5 describes the estimation of the false discovery rate using a target-decoy approach for CL-MS. Section 6 introduces the downstream applications. Finally, Section 7 concludes the chapter with some discussions of remaining issues in the identification of cross-linked peptides.