title: k-Nearest neighbor models for microarray gene expression analysis and clinical outcome prediction.
abstract: In the clinical application of genomic data analysis and modeling, a number of factors contribute to the performance of disease classification and clinical outcome prediction. This study focuses on the k-nearest neighbor (KNN) modeling strategy and its clinical use. Although KNN is simple and clinically appealing, large performance variations were found among experienced data analysis teams in the MicroArray Quality Control Phase II (MAQC-II) project. For clinical end points and controls from breast cancer, neuroblastoma and multiple myeloma, we systematically generated 463,320 KNN models by varying feature ranking method, number of features, distance metric, number of neighbors, vote weighting and decision threshold. We identified factors that contribute to the MAQC-II project performance variation, and validated a KNN data analysis protocol using a newly generated clinical data set with 478 neuroblastoma patients. We interpreted the biological and practical significance of the derived KNN models, and compared their performance with existing clinical factors.
authors.affiliation: Biomedical Engineering Department, Georgia Institute of Technology and Emory University, Atlanta, GA, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Parry
authors.forename: W
authors.initials: W
authors.lastname: Jones
authors.forename: T H
authors.initials: TH
authors.lastname: Stokes
authors.forename: J H
authors.initials: JH
authors.lastname: Phan
authors.forename: R A
authors.initials: RA
authors.lastname: Moffitt
authors.forename: H
authors.initials: H
authors.lastname: Fang
authors.forename: L
authors.initials: L
authors.lastname: Shi
authors.forename: A
authors.initials: A
authors.lastname: Oberthuer
authors.forename: M
authors.initials: M
authors.lastname: Fischer
authors.forename: W
authors.initials: W
authors.lastname: Tong
authors.forename: M D
authors.initials: MD
authors.lastname: Wang
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics; D018572:Disease-Free Survival; D023381:Endpoint Determination / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D016015:Logistic Models; D015233:Models, Statistical; D009101:Multiple Myeloma / Q000188:drug therapy / Q000235:genetics; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000188:drug therapy / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis / Q000706:statistics & numerical data*; D011237:Predictive Value of Tests; D011786:Quality Control; D018570:Risk Assessment; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor