Supplementary Figure 3: Details on the different data analysis steps performed by the RNP^xl tool.

First, spectra of small precursors and those corresponding to short RNA oligonucleotides according to their fractional mass are filtered from the input mzML file. Next, the masses for all possible nucleotide combinations as defined in the tool’s parameters are calculated and subsequently subtracted from all precursor masses to yield the precursor mass variants. One mzML file for each spectrum is created, containing the original experimental precursor mass as well as all its precursor mass variants together with the unaltered MS/MS fragment information. These are submitted into the database search engine. Then, the tool summarizes the search results, retaining the best scoring hit per spectrum and annotates the cross-linked RNA moiety according to the mass difference between experimental precursor mass and the precursor mass variant that gave rise to the database search result. Finally, the results are summarized in csv and idXML format.