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However, the vast number of potential combinations of cross-linked residues or sites obtained with such a cross-linker makes the data challenging to analyze, especially for the proteome-wide applications. Here, we developed SpotLink software for identifying site nonspecific cross-links at the proteome scale. Contributed by the dual pointer dynamic pruning algorithm and the quality control of cross-linking sites, SpotLink identified &amp;gt; 3000 cross-links from human cell samples within a short period of days. We demonstrated that SpotLink outperformed other approaches in terms of sensitivity and precision on the datasets of the simulated succinimidyl 4,4\u2032-azipentanoate dataset and the condensin complexes with known structures. In addition, some valuable PPI were discovered in the datasets of the condensin complexes and the HeLa dataset, indicating the unique identification advantages of site nonspecific cross-linking. These findings reinforce the importance of SpotLink as a fundamental characteristic of site nonspecific cross-linking technologies.<\/jats:p>","DOI":"10.1093\/bib\/bbac316","type":"journal-article","created":{"date-parts":[[2022,9,12]],"date-time":"2022-09-12T08:53:56Z","timestamp":1662972836000},"source":"Crossref","is-referenced-by-count":6,"title":["SpotLink enables sensitive and precise identification of site nonspecific cross-links at the proteome scale"],"prefix":"10.1093","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5720-3130","authenticated-orcid":false,"given":"Weijie","family":"Zhang","sequence":"first","affiliation":[{"name":"CAS Key Laboratory of Separation Science for Analytical Chemistry , National Chromatographic R. & A. Center, Dalian Institute of Chemical Physics, , Dalian, Liaoning 116023 , China"},{"name":"Chinese Academy of Sciences , National Chromatographic R. & A. Center, Dalian Institute of Chemical Physics, , Dalian, Liaoning 116023 , China"},{"name":"University of Chinese Academy of Sciences , Beijing 100039 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengyun","family":"Gong","sequence":"additional","affiliation":[{"name":"School of Engineering Medicine & School of Biological Science and Medical Engineering, Beihang University , Beijing, 100191 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yichu","family":"Shan","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Separation Science for Analytical Chemistry , National Chromatographic R. & A. Center, Dalian Institute of Chemical Physics, , Dalian, Liaoning 116023 , China"},{"name":"Chinese Academy of Sciences , National Chromatographic R. & A. Center, Dalian Institute of Chemical Physics, , Dalian, Liaoning 116023 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Zhao","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Separation Science for Analytical Chemistry , National Chromatographic R. & A. Center, Dalian Institute of Chemical Physics, , Dalian, Liaoning 116023 , China"},{"name":"Chinese Academy of Sciences , National Chromatographic R. & A. Center, Dalian Institute of Chemical Physics, , Dalian, Liaoning 116023 , China"},{"name":"University of Chinese Academy of Sciences , Beijing 100039 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongke","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Engineering Medicine & School of Biological Science and Medical Engineering, Beihang University , Beijing, 100191 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiushi","family":"Wei","sequence":"additional","affiliation":[{"name":"School of Engineering Medicine & School of Biological Science and Medical Engineering, Beihang University , Beijing, 100191 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Liang","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Separation Science for Analytical Chemistry , National Chromatographic R. & A. Center, Dalian Institute of Chemical Physics, , Dalian, Liaoning 116023 , China"},{"name":"Chinese Academy of Sciences , National Chromatographic R. & A. Center, Dalian Institute of Chemical Physics, , Dalian, Liaoning 116023 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Engineering Medicine & School of Biological Science and Medical Engineering, Beihang University , Beijing, 100191 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2543-1547","authenticated-orcid":false,"given":"Lihua","family":"Zhang","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Separation Science for Analytical Chemistry , National Chromatographic R. & A. Center, Dalian Institute of Chemical Physics, , Dalian, Liaoning 116023 , China"},{"name":"Chinese Academy of Sciences , National Chromatographic R. & A. Center, Dalian Institute of Chemical Physics, , Dalian, Liaoning 116023 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukui","family":"Zhang","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Separation Science for Analytical Chemistry , National Chromatographic R. & A. Center, Dalian Institute of Chemical Physics, , Dalian, Liaoning 116023 , China"},{"name":"Chinese Academy of Sciences , National Chromatographic R. & A. 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