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The current available drugs for AD provide symptomatic benefit, but there is no effective drug to cure the disease. The emergence of large-scale genomic, pharmacological data provides new opportunities for drug discovery and drug repositioning as a promising strategy in searching novel drug for AD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In this study, we took advantage of our increasing understanding based on systems biology approaches on the pathway and network levels and perturbation datasets from the Library of Integrated Network-Based Cellular Signatures to introduce a systematic computational process to discover new drugs implicated in AD. First, we collected 561 genes that have reported to be risk genes of AD, and applied functional enrichment analysis on these genes. Then, by quantifying proximity between 5595 molecule drugs and AD based on human interactome, we filtered out 1092 drugs that were proximal to the disease. We further performed an Inverted Gene Set Enrichment analysis on these drug candidates, which allowed us to estimate effect of perturbations on gene expression and identify 24 potential drug candidates for AD treatment. Results from this study also provided insights for understanding the molecular mechanisms underlying AD. As a useful systematic method, our approach can also be used to identify efficacious therapies for other complex diseases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Availability and implementation<\/jats:title><jats:p>The source code is available at https:\/\/github.com\/zer0o0\/drug-repo.git.<\/jats:p><\/jats:sec><jats:sec><jats:title>Supplementary information<\/jats:title><jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p><\/jats:sec>","DOI":"10.1093\/bioinformatics\/btaa563","type":"journal-article","created":{"date-parts":[[2020,6,3]],"date-time":"2020-06-03T19:12:02Z","timestamp":1591211522000},"page":"4626-4632","source":"Crossref","is-referenced-by-count":46,"title":["Screening novel drug candidates for Alzheimer\u2019s disease by an integrated network and transcriptome analysis"],"prefix":"10.1093","volume":"36","author":[{"given":"Yonglin","family":"Peng","sequence":"first","affiliation":[{"name":"School of Biomedical Engineering and Technology, Tianjin Medical University , Tianjin 300070 China"}]},{"given":"Meng","family":"Yuan","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering and Technology, Tianjin Medical University , Tianjin 300070 China"}]},{"given":"Juncai","family":"Xin","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering and Technology, Tianjin Medical University , Tianjin 300070 China"}]},{"given":"Xinhua","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering and Technology, Tianjin Medical University , Tianjin 300070 China"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6514-0923","authenticated-orcid":false,"given":"Ju","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering and Technology, Tianjin Medical University , Tianjin 300070 China"}]}],"member":"286","published-online":{"date-parts":[[2020,6,9]]},"reference":[{"key":"2023062213561944400_btaa563-B1","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.pnpbp.2018.05.010","article-title":"Targeting central beta2 receptors ameliorates streptozotocin-induced neuroinflammation via inhibition of glycogen synthase kinase3 pathway in mice","volume":"86","author":"Abdel Rasheed","year":"2018","journal-title":"Prog. 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