title: An automated PLS search for biologically relevant QSAR descriptors.
abstract: An automated PLS engine, WB-PLS, was applied to 1632 QSAR series with at least 25 compounds per series extracted from WOMBAT (WOrld of Molecular BioAcTivity). WB-PLS extracts a single Y variable per series, as well as pre-computed X variables from a table. The table contained 2D descriptors, the drug-like MDL 320 keys as implemented in the Mesa A&C Fingerprint module, and in-house generated topological-pharmacophore SMARTS counts and fingerprints. Each descriptor type was treated as a block, with or without scaling. Cross-validation, variable importance on projections (VIP) above 0.8 and q2 > or = 0.3 were applied for model significance. Among cross-validation methods, leave-one-in-seven-out (CV7) is a better measure of model significance, compared to leave-one-out (measuring redundancy) and leave-half-out (too restrictive). SMARTS counts overlap with 2D descriptors (having a more quantitative nature), whereas MDL keys overlap with in-house fingerprints (both are more qualitative). The SMARTS counts is the most effective descriptor system, when compared to the other three. At the individual level, size-related descriptors and topological indices (in the 2D property space), and branched SMARTS, aromatic and ring atom types and halogens are found to be most relevant according to the VIP criterion.
authors.affiliation: Division of Biocomputing, University of New Mexico School of Medicine, I University of New Mexico, MSC08 4560, Albuquerque, NM 87131, USA.
authors.forename: Marius
authors.initials: M
authors.lastname: Olah
authors.forename: Cristian
authors.initials: C
authors.lastname: Bologa
authors.forename: Tudor I
authors.initials: TI
authors.lastname: Oprea
mesh_terms: D001331:Automation; D016208:Databases, Factual; D016247:Information Storage and Retrieval; D021281:Quantitative Structure-Activity Relationship
references.citation: J Comput Aided Mol Des. 2003 Feb-Apr;17(2-4):241-53
references.pmid: 13677490
references.citation: J Chem Inf Comput Sci. 2000 Sep-Oct;40(5):1160-8
references.pmid: 11045809
references.citation: J Med Chem. 1973 Jul;16(7):745-9
references.pmid: 4146906
references.citation: J Med Chem. 1964 Jul;7:395-9
references.pmid: 14221113
references.citation: J Comput Aided Mol Des. 2001 Aug;15(8):741-52
references.pmid: 11718478
references.citation: J Chem Inf Comput Sci. 2002 Nov-Dec;42(6):1273-80
references.pmid: 12444722
references.citation: J Med Chem. 2002 Nov 7;45(23):5069-80
references.pmid: 12408718
references.citation: J Am Chem Soc. 1988 Aug 1;110(18):5959-67
references.pmid: 22148765
references.citation: J Chem Inf Comput Sci. 2003 Jan-Feb;43(1):120-5
references.pmid: 12546544
references.citation: J Chem Inf Comput Sci. 2000 Mar;40(2):195-209
references.pmid: 10761119
references.citation: J Chem Inf Comput Sci. 2003 Nov-Dec;43(6):1882-9
references.pmid: 14632437
references.citation: J Chem Inf Comput Sci. 2001 Sep-Oct;41(5):1208-17
references.pmid: 11604020
references.citation: J Comput Aided Mol Des. 2000 Mar;14(3):251-64
references.pmid: 10756480
references.citation: Chem Rev. 2002 Mar;102(3):783-812
references.pmid: 11890757
references.citation: J Comput Aided Mol Des. 1994 Aug;8(4):457-66
references.pmid: 7815097
references.citation: Angew Chem Int Ed Engl. 1999 Oct 4;38(19):2894-2896
references.pmid: 10540384
references.citation: J Med Chem. 1985 Jul;28(7):849-57
references.pmid: 3892003
references.citation: J Comb Chem. 2001 Mar-Apr;3(2):157-66
references.pmid: 11300855
references.citation: J Chem Inf Comput Sci. 2000 Jul;40(4):891-8
references.pmid: 10955515