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However, there is no consensus on which methodologies and parameters are the most optimal to conduct such analysis. Aiming to fill this gap, new benchmarking standards were developed to quantitatively evaluate drug retrieval performance. Investigations of potential factors influencing drug retrieval were conducted based on these standards. As a result, we determined an optimal approach for LINCS data-based therapeutic discovery. With this approach, homoharringtonine (HHT) was identified to be a candidate agent with potential therapeutic and preventive effects on liver cancer. The antitumor and antifibrotic activity of HHT was validated experimentally using subcutaneous xenograft tumor model and carbon tetrachloride (CCL\n                    <jats:sub>4<\/jats:sub>\n                    )-induced liver fibrosis model, demonstrating the reliability of the prediction results. In summary, our findings will not only impact the future applications of LINCS data but also offer new opportunities for therapeutic intervention of liver cancer.\n                  <\/jats:p>","DOI":"10.7554\/elife.71880","type":"journal-article","created":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T14:15:11Z","timestamp":1645193711000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.71880","source":"Crossref","is-referenced-by-count":152,"title":["A survey of optimal strategy for signature-based drug repositioning and an application to liver cancer"],"prefix":"10.7554","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1237-2632","authenticated-orcid":true,"given":"Chen","family":"Yang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03ypbx660","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory of Oncogenes and Related Genes, Department of Liver Surgery & Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong 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