Decision Tree Searching Strategy to Boost the Identification of Cross-Linked Peptides

We
describe an efficient decision tree searching strategy (DTSS)
to boost the identification of cross-linked peptides. The DTSS approach
allows the identification of a wealth of complementary information
to facilitate the construction of more protein–protein interaction
networks for human cell lysate, which was tested by the use of a recently
reported cross-linking data set (ACS Cent. Sci. 2019, 5, 1514–1522). A variant of
the PhoX-linker, named pDSPE, was synthesized and applied
to cross-link Escherichia coli cell
lysate to demonstrate that the acquisition of doubly charged ions
can significantly improve identification results. The method can be
seamlessly integrated to other search engines to maximize the number
of identified cross-links.