title: A ranking method for the concurrent learning of compounds with various activity profiles.
abstract: BACKGROUND
  In this study, we present a SVM-based ranking algorithm for the concurrent learning of compounds with different activity profiles and their varying prioritization. To this end, a specific labeling of each compound was elaborated in order to infer virtual screening models against multiple targets. We compared the method with several state-of-the-art SVM classification techniques that are capable of inferring multi-target screening models on three chemical data sets (cytochrome P450s, dehydrogenases, and a trypsin-like protease data set) containing three different biological targets each.
  
  
  RESULTS
  The experiments show that ranking-based algorithms show an increased performance for single- and multi-target virtual screening. Moreover, compounds that do not completely fulfill the desired activity profile are still ranked higher than decoys or compounds with an entirely undesired profile, compared to other multi-target SVM methods.
  
  
  CONCLUSIONS
  SVM-based ranking methods constitute a valuable approach for virtual screening in multi-target drug design. The utilization of such methods is most helpful when dealing with compounds with various activity profiles and the finding of many ligands with an already perfectly matching activity profile is not to be expected.
authors: Center for Bioinformatics Tübingen (ZBIT), University of Tuebingen, Sand 1, Tübingen, 72076 Germany.
authors: Alexander
authors: A
authors: Dörr
authors: Center for Bioinformatics Tübingen (ZBIT), University of Tuebingen, Sand 1, Tübingen, 72076 Germany.
authors: Lars
authors: L
authors: Rosenbaum
authors: Center for Bioinformatics Tübingen (ZBIT), University of Tuebingen, Sand 1, Tübingen, 72076 Germany.
authors: Andreas
authors: A
authors: Zell
keywords: Machine learning; Multi-target; Ranking; Support vector machine; Virtual screening
references: Nucleic Acids Res. 2012 Jan;40(Database issue):D400-12
references: 22140110
references: Nat Biotechnol. 2007 Oct;25(10):1110-1
references: 17921993
references: Mol Cancer Ther. 2006 May;5(5):1136-44
references: 16731745
references: J Cheminform. 2011 Mar 25;3(1):11
references: 21439031
references: J Chem Inf Model. 2009 Apr;49(4):756-66
references: 19391629
references: J Chem Inf Model. 2005 May-Jun;45(3):549-61
references: 15921445
references: J Chem Inf Model. 2013 Apr 22;53(4):791-801
references: 23517241
references: J Chem Inf Model. 2010 Jul 26;50(7):1189-204
references: 20572635
references: Nat Rev Drug Discov. 2007 Mar;6(3):202-10
references: 17318209
references: J Med Chem. 2005 Oct 20;48(21):6523-43
references: 16220969
references: Drug Discov Today. 2007 Jan;12(1-2):34-42
references: 17198971
references: Trends Pharmacol Sci. 2005 Apr;26(4):178-82
references: 15808341
references: J Chem Inf Model. 2009 Oct;49(10):2155-67
references: 19780576
references: Endocr Relat Cancer. 2006 Dec;13 Suppl 1:S15-24
references: 17259554
references: Expert Opin Drug Discov. 2007 Jun;2(6):799-808
references: 23488998
references: J Chem Inf Model. 2009 Apr;49(4):767-79
references: 19309114
references: J Cheminform. 2011 Jan 10;3(1):3
references: 21219648
references: J Chem Inf Model. 2011 Jan 24;51(1):83-92
references: 21166393
references: J Chem Inf Comput Sci. 2003 Mar-Apr;43(2):493-500
references: 12653513
references: J Chem Inf Model. 2010 May 24;50(5):716-31
references: 20387860
references: Nat Rev Drug Discov. 2004 Aug;3(8):673-83
references: 15286734
references: Nat Rev Drug Discov. 2002 Nov;1(11):882-94
references: 12415248
references: Mol Biosyst. 2009 Sep;5(9):1051-7
references: 19668871
references: Pharm Res. 2010 May;27(5):739-49
references: 20221898
references: J Chem Inf Model. 2010 May 24;50(5):742-54
references: 20426451
references: Nat Rev Drug Discov. 2004 Apr;3(4):353-9
references: 15060530
references: J Med Chem. 2010 Feb 25;53(4):1413-37
references: 20166671
references: Nature. 2007 Jan 25;445(7126):437-41
references: 17206155
references: Nucleic Acids Res. 2007 Jan;35(Database issue):D198-201
references: 17145705
references: Bioorg Med Chem. 2006 Feb 15;14(4):896-7
references: 16203151
references: J Biol Chem. 2006 Sep 8;281(36):25903-14
references: 16847054
references: J Proteomics. 2011 Nov 18;74(12):2554-74
references: 21621023
references: J Chem Inf Comput Sci. 2004 Jan-Feb;44(1):170-8
references: 14741025
references: Curr Pharm Des. 2006;12(17):2111-20
references: 16796559
references: J Cheminform. 2013 Jul 11;5(1):33
references: 23842210
references: PLoS One. 2012;7(6):e40262
references: 22768266