Abstract
The notion of repurposing of existing drugs to treat both common and rare diseases has gained traction from both academia and pharmaceutical companies. Given the high attrition rates, massive time, money, and effort of brand-new drug development, the advantages of drug repurposing in terms of lower costs and shorter development time have become more appealing. Computational drug repurposing is promising approach and has shown great potential in tailoring genomic findings to the development of treatments for diseases. However, there are still challenges involved in building a standard computational drug repurposing solution for high-throughput analysis and the implementation to clinical practice. In this study, we applied the computational drug repurposing approaches for Ulcerative Colitis (UC) patients to provide better treatment for this disabling disease. Repositioning drug candidates were identified, and these findings provide a potentially effective therapeutics for the treatment of UC patients. This preliminary computational drug repurposing pipeline will be extended in the near future to help realize the full potential of drug repurposing.
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References
Chen, B., et al.: Reversal of cancer gene expression correlates with drug efficacy and reveals therapeutic targets. Nat. Commun. 8, ncomms16022 (2017)
Chumanevich, A.A., et al.: Repurposing the anti-malarial drug, quinacrine: new anti-colitis properties. Oncotarget 7(33), 52928 (2016)
De Zoeten, E.F., Wang, L., Sai, H., Dillmann, W.H., Hancock, W.W.: Inhibition of HDAC9 increases T regulatory cell function and prevents colitis in mice. Gastroenterology 138(2), 583–594 (2010)
Edwards, A.J., Pender, S.L.: Histone deacetylase inhibitors and their potential role in inflammatory bowel diseases (2011)
Glauben, R., et al.: Histone hyperacetylation is associated with amelioration of experimental colitis in mice. J. Immunol. 176(8), 5015–5022 (2006)
Glauben, R., et al.: Histone deacetylases: novel targets for prevention of colitis-associated cancer in mice. Gut 57(5), 613–622 (2008)
Grenier, L., Hu, P.: Computational drug repurposing for inflammatory bowel disease using genetic information. Comput. Struct. Biotechnol. J. 17, 127–135 (2019)
Huang, X.L., et al.: PI3K/Akt signaling pathway is involved in the pathogenesis of ulcerative colitis. Inflamm. Res. 60(8), 727–734 (2011)
Kanehisa, M., Goto, S., Furumichi, M., Tanabe, M., Hirakawa, M.: KEGG for representation and analysis of molecular networks involving diseases and drugs. Nucleic Acids Res. 38(Suppl. 1), D355–D360 (2009)
Khan, M.W., et al.: PI3K/Akt signaling is essential for communication between tissue-infiltrating mast cells, macrophages, and epithelial cells in colitis-induced cancer. Clin. Cancer Res. 19(9), 2342–2354 (2013)
Koleti, A., et al.: Data portal for the library of integrated network-based cellular signatures (LINCS) program: integrated access to diverse large-scale cellular perturbation response data. Nucleic Acids Res. 46(D1), D558–D566 (2017)
Lamb, J., et al.: The connectivity map: using gene-expression signatures to connect small molecules, genes, and disease. Science 313(5795), 1929–1935 (2006)
Lin, L., Sun, Y., Wang, D., Zheng, S., Zhang, J., Zheng, C.: Celastrol ameliorates ulcerative colitis-related colorectal cancer in mice via suppressing inflammatory responses and epithelial-mesenchymal transition. Front. Pharmacol. 6, 320 (2016)
Massey, D., Bredin, F., Parkes, M.: Use of sirolimus (rapamycin) to treat refractory Crohn’s disease. Gut 57(9), 1294–1296 (2008)
Mutalib, M., et al.: The use of sirolimus (rapamycin) in the management of refractory inflammatory bowel disease in children. J. Crohn’s Colitis 8(12), 1730–1734 (2014)
Sheridan, C., Downward, J.: Inhibiting the RAS-PI3K pathway in cancer therapy. In: The Enzymes, vol. 34, pp. 107–136. Elsevier (2013)
Sirota, M., et al.: Discovery and preclinical validation of drug indications using compendia of public gene expression data. Sci. Transl. Med. 3(96), 96ra77 (2011)
So, H.C., et al.: Analysis of genome-wide association data highlights candidates for drug repositioning in psychiatry. Nat. Neurosci. 20(10), 1342 (2017)
Yin, H., et al.: Sirolimus ameliorates inflammatory responses by switching the regulatory T/T helper type 17 profile in murine colitis. Immunology 139(4), 494–502 (2013)
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Kim, S., Thapa, I., Zhang, L., Ali, H. (2019). On Identifying Candidates for Drug Repurposing for the Treatment of Ulcerative Colitis using Gene Expression Data. In: Rojas, I., Valenzuela, O., Rojas, F., Ortuño, F. (eds) Bioinformatics and Biomedical Engineering. IWBBIO 2019. Lecture Notes in Computer Science(), vol 11465. Springer, Cham. https://doi.org/10.1007/978-3-030-17938-0_45
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DOI: https://doi.org/10.1007/978-3-030-17938-0_45
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