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However, there is no comprehensive evaluation for these state-of-the-art methods. Here, we conducted a performance assessment for 16 SSC analysis workflows by using the combination of 4 sample-specific network reconstruction methods and 4 representative structural control methods. This study includes simulation evaluation of representative biological networks, personalized driver genes prioritization on multiple cancer bulk expression datasets with matched patient samples from TCGA, and cell marker genes and key time point identification related to cell differentiation on single-cell RNA-seq datasets. By widely comparing analysis of existing SSC analysis workflows, we provided the following recommendations and banchmarking workflows. (i) The performance of a network control method is strongly dependent on the up-stream sample-specific network method, and Cell-Specific Network construction (CSN) method and Single-Sample Network (SSN) method are the preferred sample-specific network construction methods. (ii) After constructing the sample-specific networks, the undirected network-based control methods are more effective than the directed network-based control methods. In addition, these data and evaluation pipeline are freely available on https:\/\/github.com\/WilfongGuo\/Benchmark_control<\/jats:ext-link>.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1008962","type":"journal-article","created":{"date-parts":[[2021,5,6]],"date-time":"2021-05-06T18:41:30Z","timestamp":1620326490000},"page":"e1008962","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":21,"title":["Performance assessment of sample-specific network control methods for bulk and single-cell biological data analysis"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0565-177X","authenticated-orcid":true,"given":"Wei-Feng","family":"Guo","sequence":"first","affiliation":[]},{"given":"Xiangtian","family":"Yu","sequence":"additional","affiliation":[]},{"given":"Qian-Qian","family":"Shi","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0811-0223","authenticated-orcid":true,"given":"Jing","family":"Liang","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1305-7447","authenticated-orcid":true,"given":"Shao-Wu","family":"Zhang","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0295-3994","authenticated-orcid":true,"given":"Tao","family":"Zeng","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2021,5,6]]},"reference":[{"key":"pcbi.1008962.ref001","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1186\/s12967-015-0546-5","article-title":"Unravelling personalized dysfunctional gene network of complex diseases based on differential network model","volume":"13","author":"X Yu","year":"2015","journal-title":"Journal of Translational Medicine"},{"issue":"3","key":"pcbi.1008962.ref002","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1093\/jmcb\/mjv025","article-title":"Diagnosing phenotypes of single-sample individuals by edge biomarkers","volume":"7","author":"W Zhang","year":"2015","journal-title":"Journal of Molecular Cell Biology"},{"key":"pcbi.1008962.ref003","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.isci.2019.03.021","article-title":"Estimating Sample-Specific Regulatory Networks","volume":"14","author":"ML Kuijjer","year":"2019","journal-title":"iScience."},{"issue":"22","key":"pcbi.1008962.ref004","doi-asserted-by":"crossref","first-page":"e164","DOI":"10.1093\/nar\/gkw772","article-title":"Personalized characterization of diseases using sample-specific networks","volume":"44","author":"X Liu","year":"2016","journal-title":"Nucleic Acids Research"},{"issue":"11","key":"pcbi.1008962.ref005","doi-asserted-by":"crossref","first-page":"e62","DOI":"10.1093\/nar\/gkz172","article-title":"Cell-specific network constructed by single-cell RNA sequencing data","volume":"47","author":"H Dai","year":"2019","journal-title":"Nucleic Acids Research"},{"issue":"5","key":"pcbi.1008962.ref006","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1093\/bib\/bbz089","article-title":"Network control principles for identifying personalized driver genes in cancer","volume":"21","author":"W-F Guo","year":"2019","journal-title":"Briefings in bioinformatics"},{"issue":"7346","key":"pcbi.1008962.ref007","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/nature10011","article-title":"Controllability of complex networks","volume":"473","author":"Y-Y Liu","year":"2011","journal-title":"Nature"},{"issue":"1","key":"pcbi.1008962.ref008","doi-asserted-by":"crossref","first-page":"5415","DOI":"10.1038\/ncomms6415","article-title":"Target control of complex networks","volume":"5","author":"J Gao","year":"2014","journal-title":"Nature Communications"},{"issue":"7","key":"pcbi.1008962.ref009","doi-asserted-by":"crossref","first-page":"073005","DOI":"10.1088\/1367-2630\/14\/7\/073005","article-title":"Dominating scale-free networks with variable scaling exponent: heterogeneous networks are not difficult to control","volume":"14","author":"JC Nacher","year":"2012","journal-title":"New Journal of Physics"},{"issue":"3","key":"pcbi.1008962.ref010","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1007\/s10884-013-9312-7","article-title":"Dynamics and Control at Feedback Vertex Sets. 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