title: Ovarian cancer detection from metabolomic liquid chromatography/mass spectrometry data by support vector machines.
abstract: BACKGROUND
  The majority of ovarian cancer biomarker discovery efforts focus on the identification of proteins that can improve the predictive power of presently available diagnostic tests. We here show that metabolomics, the study of metabolic changes in biological systems, can also provide characteristic small molecule fingerprints related to this disease.
  
  
  RESULTS
  In this work, new approaches to automatic classification of metabolomic data produced from sera of ovarian cancer patients and benign controls are investigated. The performance of support vector machines (SVM) for the classification of liquid chromatography/time-of-flight mass spectrometry (LC/TOF MS) metabolomic data focusing on recognizing combinations or "panels" of potential metabolic diagnostic biomarkers was evaluated. Utilizing LC/TOF MS, sera from 37 ovarian cancer patients and 35 benign controls were studied. Optimum panels of spectral features observed in positive or/and negative ion mode electrospray (ESI) MS with the ability to distinguish between control and ovarian cancer samples were selected using state-of-the-art feature selection methods such as recursive feature elimination and L1-norm SVM.
  
  
  CONCLUSIONS
  Three evaluation processes (leave-one-out-cross-validation, 12-fold-cross-validation, 52-20-split-validation) were used to examine the SVM models based on the selected panels in terms of their ability for differentiating control vs. disease serum samples. The statistical significance for these feature selection results were comprehensively investigated. Classification of the serum sample test set was over 90% accurate indicating promise that the above approach may lead to the development of an accurate and reliable metabolomic-based approach for detecting ovarian cancer.
authors.affiliation: College of Computing, Georgia Institute of Technology, Atlanta GA 30332, USA. wguan@cc.gatech.edu
authors.forename: Wei
authors.initials: W
authors.lastname: Guan
authors.forename: Manshui
authors.initials: M
authors.lastname: Zhou
authors.forename: Christina Y
authors.initials: CY
authors.lastname: Hampton
authors.forename: Benedict B
authors.initials: BB
authors.lastname: Benigno
authors.forename: L Deette
authors.initials: LD
authors.lastname: Walker
authors.forename: Alexander
authors.initials: A
authors.lastname: Gray
authors.forename: John F
authors.initials: JF
authors.lastname: McDonald
authors.forename: Facundo M
authors.initials: FM
authors.lastname: Fernández
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D002853:Chromatography, Liquid / Q000379:methods*; D019295:Computational Biology / Q000379:methods*; D005260:Female; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000175:diagnosis*; D010363:Pattern Recognition, Automated / Q000379:methods
references.citation: Clin Chem. 2002 Aug;48(8):1296-304
references.pmid: 12142387
references.citation: Proteomics. 2005 Nov;5(17):4625-36
references.pmid: 16220531
references.citation: J Comput Biol. 2003;10(2):119-42
references.pmid: 12804087
references.citation: Stat Appl Genet Mol Biol. 2008;7(2):Article11
references.pmid: 18312216
references.citation: JAMA. 2002 Jun 19;287(23):3081-2
references.pmid: 12069669
references.citation: BMC Cancer. 2009 Apr 05;9:104
references.pmid: 19344524
references.citation: Gynecol Oncol. 1990 Aug;38(2):181-6
references.pmid: 2387533
references.citation: Int J Cancer. 2005 Feb 20;113(5):782-8
references.pmid: 15499633
references.citation: Bioinformatics. 2001 Jun;17(6):509-19
references.pmid: 11395427
references.citation: Lancet. 2002 Feb 16;359(9306):572-7
references.pmid: 11867112
references.citation: Bioinformatics. 2008 Dec 15;24(24):2908-14
references.pmid: 18815183
references.citation: Artif Intell Med. 2004 Oct;32(2):71-83
references.pmid: 15364092
references.citation: Talanta. 2006 Feb 28;68(5):1683-91
references.pmid: 18970515
references.citation: BMC Bioinformatics. 2003 Nov 06;4:54
references.pmid: 14604446
references.citation: Endocr Relat Cancer. 2004 Jun;11(2):163-78
references.pmid: 15163296
references.citation: Bioinformatics. 2003 Sep 1;19(13):1636-43
references.pmid: 12967959
references.citation: BMC Bioinformatics. 2007 Mar 27;8:105
references.pmid: 17389044
references.citation: Am J Pharmacogenomics. 2005;5(5):281-92
references.pmid: 16196498
references.citation: Obstet Gynecol. 1971 Sep;38(3):427-35
references.pmid: 4999312
references.citation: Cancer Epidemiol Biomarkers Prev. 2004 Jul;13(7):1185-91
references.pmid: 15247129
references.citation: J Proteome Res. 2007 Feb;6(2):443-58
references.pmid: 17269702
references.citation: Cancer. 1987 Aug 1;60(3):353-61
references.pmid: 3594371
references.citation: J Proteome Res. 2007 Feb;6(2):469-79
references.pmid: 17269704
references.citation: Proteomics. 2001 Oct;1(10):1205-15
references.pmid: 11721633
references.citation: Mass Spectrom Rev. 2007 Jan-Feb;26(1):51-78
references.pmid: 16921475
references.citation: BMC Bioinformatics. 2006 Aug 19;7:387
references.pmid: 16919171
references.citation: Cancer Inform. 2007 Dec 11;3:329-39
references.pmid: 19455252
references.citation: Tumour Biol. 1992;13(3):121-32
references.pmid: 1626178
references.citation: Rapid Commun Mass Spectrom. 2008 Oct;22(19):3061-8
references.pmid: 18767022
references.citation: JAMA. 1998 Aug 26;280(8):719-23
references.pmid: 9728644
references.citation: Bioinformatics. 2005 May 15;21(10):2200-9
references.pmid: 15784749
references.citation: Med Care. 2002 Aug;40(8 Suppl):IV-104-17
references.pmid: 12187175
references.citation: Surg Gynecol Obstet. 1989 Apr;168(4):296-301
references.pmid: 2928903
references.citation: Bioinformatics. 2006 Mar 1;22(5):634-6
references.pmid: 16403790
references.citation: Proteomics. 2003 Apr;3(4):433-9
references.pmid: 12687611
references.citation: J Proteome Res. 2007 Aug;6(8):2936-62
references.pmid: 17583933
references.citation: Obstet Gynecol. 1989 Sep;74(3 Pt 1):379-83
references.pmid: 2761915