title: A survey of current trends in computational drug repositioning.
abstract: Computational drug repositioning or repurposing is a promising and efficient tool for discovering new uses from existing drugs and holds the great potential for precision medicine in the age of big data. The explosive growth of large-scale genomic and phenotypic data, as well as data of small molecular compounds with granted regulatory approval, is enabling new developments for computational repositioning. To achieve the shortest path toward new drug indications, advanced data processing and analysis strategies are critical for making sense of these heterogeneous molecular measurements. In this review, we show recent advancements in the critical areas of computational drug repositioning from multiple aspects. First, we summarize available data sources and the corresponding computational repositioning strategies. Second, we characterize the commonly used computational techniques. Third, we discuss validation strategies for repositioning studies, including both computational and experimental methods. Finally, we highlight potential opportunities and use-cases, including a few target areas such as cancers. We conclude with a brief discussion of the remaining challenges in computational drug repositioning.
authors.forename: Jiao
authors.initials: J
authors.lastname: Li
authors.forename: Si
authors.initials: S
authors.lastname: Zheng
authors.forename: Bin
authors.initials: B
authors.lastname: Chen
authors.forename: Atul J
authors.initials: AJ
authors.lastname: Butte
authors.forename: S Joshua
authors.initials: SJ
authors.lastname: Swamidass
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Lu
mesh_terms: D019295:Computational Biology / Q000639:trends; D057225:Data Mining; D004338:Drug Combinations; D058492:Drug Repositioning / Q000706:statistics & numerical data / Q000639:trends*; D023281:Genomics; D006801:Humans; D000069550:Machine Learning; D015394:Molecular Structure; D010641:Phenotype; D011795:Surveys and Questionnaires
chemical_list: D004338:Drug Combinations
keywords: chemical structure; computational drug repositioning; drug combination; genome; integrative strategies; phenome; prediction validation
references.citation: PLoS Comput Biol. 2012;8(7):e1002574
references.pmid: 22859915
references.citation: Discov Med. 2004 Jun;4(22):172-9
references.pmid: 20704981
references.citation: Genome Med. 2012 Mar 30;4(3):27
references.pmid: 22494857
references.citation: Proc Natl Acad Sci U S A. 2015 Jan 27;112(4):1167-72
references.pmid: 25092317
references.citation: Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
references.pmid: 16199517
references.citation: Database (Oxford). 2014;2014. pii: bau039. doi: 10.1093/database/bau039
references.pmid: 24852177
references.citation: Nat Biotechnol. 2012 Apr;30(4):317-20
references.pmid: 22491277
references.citation: Retina. 2006 May-Jun;26(5):495-511
references.pmid: 16770255
references.citation: Nature. 2009 Sep 10;461(7261):218-23
references.pmid: 19741703
references.citation: Chin J Cancer. 2014 Mar;33(3):140-7
references.pmid: 24016392
references.citation: Nucleic Acids Res. 2000 Jan 1;28(1):235-42
references.pmid: 10592235
references.citation: Pac Symp Biocomput. 2012;:388-99
references.pmid: 22174294
references.citation: Nat Biotechnol. 2007 Oct;25(10):1119-26
references.pmid: 17921997
references.citation: Bioinformatics. 2008 Jun 1;24(11):1413-5
references.pmid: 18417489
references.citation: Mol Syst Biol. 2010;6:343
references.pmid: 20087340
references.citation: Immunology. 2014 Feb;141(2):157-65
references.pmid: 24147732
references.citation: Am J Respir Crit Care Med. 2012 Dec 1;186(11):1180-8
references.pmid: 23024022
references.citation: Bioinformatics. 2013 Feb 1;29(3):409-11
references.pmid: 23220571
references.citation: PLoS Comput Biol. 2010;6(9). pii: e1000925. doi: 10.1371/journal.pcbi.1000925
references.pmid: 20838579
references.citation: Proc Natl Acad Sci U S A. 2013 Feb 26;110(9):3507-12
references.pmid: 23401516
references.citation: Drug Discov Today. 2013 Apr;18(7-8):350-7
references.pmid: 22897878
references.citation: J Exp Med. 2013 Oct 21;210(11):2205-21
references.pmid: 24127489
references.citation: Brief Bioinform. 2011 Jul;12(4):357-68
references.pmid: 21712342
references.citation: Mol Cancer Ther. 2013 Jul;12(7):1299-309
references.pmid: 23657945
references.citation: PLoS One. 2014;9(2):e87864
references.pmid: 24505324
references.citation: J Cancer Res Clin Oncol. 2013 Dec;139(12):2133-40
references.pmid: 24135855
references.citation: Methods Mol Biol. 2014;1159:253-67
references.pmid: 24788271
references.citation: BMC Bioinformatics. 2013;14 Suppl 16:S3
references.pmid: 24564553
references.citation: J Biomed Inform. 2012 Oct;45(5):870-8
references.pmid: 22546622
references.citation: BMC Bioinformatics. 2013;14:288
references.pmid: 24088245
references.citation: Mol Syst Biol. 2011;7:496
references.pmid: 21654673
references.citation: Sci Rep. 2014;4:7160
references.pmid: 25418113
references.citation: Sci Rep. 2012;2:282
references.pmid: 22355792
references.citation: Cancer Discov. 2013 Dec;3(12):1416-29
references.pmid: 24056683
references.citation: Database (Oxford). 2009;2009:bap018
references.pmid: 20157491
references.citation: Bioinformatics. 2013 Nov 15;29(22):2909-17
references.pmid: 23969135
references.citation: Pac Symp Biocomput. 2014;:172-82
references.pmid: 24297544
references.citation: Science. 2014 Aug 15;345(6198):718-9
references.pmid: 25124404
references.citation: PLoS One. 2014;9(7):e102221
references.pmid: 25029499
references.citation: Nat Biotechnol. 2013 Dec;31(12):1102-10
references.pmid: 24270849
references.citation: Database (Oxford). 2011;2011:baq036
references.pmid: 21245076
references.citation: Acta Biochim Biophys Sin (Shanghai). 2014 Mar;46(3):233-9
references.pmid: 24492536
references.citation: Cancer. 2012 Aug 1;118(15):3703-9
references.pmid: 22139894
references.citation: Cancer. 2013 Mar 1;119(5):955-62
references.pmid: 23165859
references.citation: PLoS One. 2013;8(11):e78518
references.pmid: 24244318
references.citation: Bioinformatics. 2013 Jan 1;29(1):132-4
references.pmid: 23129297
references.citation: Brief Bioinform. 2014 Jul;15(4):648-59
references.pmid: 23376192
references.citation: JAMA. 2014 May;311(20):2063-4
references.pmid: 24867009
references.citation: Mol Biosyst. 2014 May;10(5):1126-38
references.pmid: 24603772
references.citation: PLoS One. 2011;6(12):e28025
references.pmid: 22205936
references.citation: Nature. 2014 Feb 20;506(7488):376-81
references.pmid: 24390342
references.citation: Nucleic Acids Res. 2011 Jan;39(Database issue):D1060-6
references.pmid: 21071407
references.citation: Bioinformatics. 2012 Jun 1;28(11):1540-1
references.pmid: 22539672
references.citation: Database (Oxford). 2015;2015. pii: bav016. doi: 10.1093/database/bav016
references.pmid: 25797061
references.citation: Front Genet. 2014 Sep 30;5:342
references.pmid: 25324859
references.citation: Biomed Res Int. 2014;2014:196858
references.pmid: 25147789
references.citation: J Med Chem. 2013 Nov 14;56(21):8377-88
references.pmid: 24088053
references.citation: Drugs Today (Barc). 2014 Jan;50(1):51-100
references.pmid: 24524105
references.citation: Genome Med. 2014 Dec 02;6(12):94
references.pmid: 25484921
references.citation: Nat Rev Drug Discov. 2004 May;3(5):451-6
references.pmid: 15136792
references.citation: Front Oncol. 2013 Dec 25;3:313
references.pmid: 24400218
references.citation: Am J Clin Exp Urol. 2014 Oct 02;2(3):219-30
references.pmid: 25374924
references.citation: Genome Biol. 2003;4(5):P3
references.pmid: 12734009
references.citation: J Chem Inf Model. 2014 Sep 22;54(9):2562-9
references.pmid: 25116798
references.citation: PLoS One. 2013;8(11):e79568
references.pmid: 24223973
references.citation: Int J Biol Sci. 2014;10(7):654-63
references.pmid: 25013375
references.citation: Brief Bioinform. 2011 Jul;12(4):327-35
references.pmid: 21715466
references.citation: Proc Natl Acad Sci U S A. 2010 Feb 23;107(8):3424-9
references.pmid: 20142509
references.citation: BMC Bioinformatics. 2014;15:267
references.pmid: 25103881
references.citation: J Biomed Inform. 2014 Dec;52:448-56
references.pmid: 25220766
references.citation: J Cheminform. 2013 Jun 22;5(1):30
references.pmid: 23800010
references.citation: Pac Symp Biocomput. 2015;:68-79
references.pmid: 25592569
references.citation: PLoS One. 2013;8(4):e61318
references.pmid: 23646105
references.citation: J Am Med Inform Assoc. 2015 Jan;22(1):179-91
references.pmid: 25053577
references.citation: Brief Bioinform. 2011 Jul;12(4):341-5
references.pmid: 21357612
references.citation: Proc Natl Acad Sci U S A. 2014 Aug 5;111(31):11365-70
references.pmid: 25049379
references.citation: Science. 2006 Sep 29;313(5795):1929-35
references.pmid: 17008526
references.citation: Bioinformatics. 2010 Feb 15;26(4):587-8
references.pmid: 20031966
references.citation: Nucleic Acids Res. 2013 Jul;41(Web Server issue):W518-22
references.pmid: 23703206
references.citation: BMC Syst Biol. 2013;7 Suppl 5:S6
references.pmid: 24564976
references.citation: Nat Commun. 2013;4:2126
references.pmid: 23839242
references.citation: Mol Cancer Ther. 2014 Jul;13(7):1929-41
references.pmid: 24785412
references.citation: Nat Rev Genet. 2014 Jan;15(1):2
references.pmid: 24322724
references.citation: Trends Endocrinol Metab. 2013 Sep;24(9):469-80
references.pmid: 23773243
references.citation: BMJ. 2011;342:d741
references.pmid: 21307112
references.citation: Proceedings (IEEE Int Conf Bioinformatics Biomed). 2012;2012:1-4
references.pmid: 25264495
references.citation: Pac Symp Biocomput. 2014;:136-47
references.pmid: 24297541
references.citation: AMIA Annu Symp Proc. 2014;2014:1258-67
references.pmid: 25954437
references.citation: Nat Rev Drug Discov. 2010 Mar;9(3):203-14
references.pmid: 20168317
references.citation: Sci Transl Med. 2011 Aug 17;3(96):96ra76
references.pmid: 21849664
references.citation: Curr Top Med Chem. 2013;13(18):2337-63
references.pmid: 24059461
references.citation: Curr Top Med Chem. 2015;15(1):5-20
references.pmid: 25579574
references.citation: Nature. 2009 Nov 12;462(7270):175-81
references.pmid: 19881490
references.citation: Proc Natl Acad Sci U S A. 2010 Aug 17;107(33):14621-6
references.pmid: 20679242
references.citation: BMC Syst Biol. 2013;7:139
references.pmid: 24330611
references.citation: Nucleic Acids Res. 2005 Jan 1;33(Database issue):D562-6
references.pmid: 15608262
references.citation: Cancer Res. 2012 Jan 1;72(1):33-44
references.pmid: 22108825
references.citation: Brief Bioinform. 2011 Jul;12(4):303-11
references.pmid: 21690101
references.citation: J Cheminform. 2015 Jan 19;7(Suppl 1 Text mining for chemistry and the CHEMDNER track):S3
references.pmid: 25810774
references.citation: Cancer Discov. 2013 Dec;3(12):1364-77
references.pmid: 24078773
references.citation: Nature. 2012 Mar 29;483(7391):570-5
references.pmid: 22460902