title: Identification by random forest method of HLA class I amino acid substitutions associated with lower survival at day 100 in unrelated donor hematopoietic cell transplantation.
abstract: The identification of important amino acid substitutions associated with low survival in hematopoietic cell transplantation (HCT) is hampered by the large number of observed substitutions compared with the small number of patients available for analysis. Random forest analysis is designed to address these limitations. We studied 2107 HCT recipients with good or intermediate risk hematological malignancies to identify HLA class I amino acid substitutions associated with reduced survival at day 100 post transplant. Random forest analysis and traditional univariate and multivariate analyses were used. Random forest analysis identified amino acid substitutions in 33 positions that were associated with reduced 100 day survival, including HLA-A 9, 43, 62, 63, 76, 77, 95, 97, 114, 116, 152, 156, 166 and 167; HLA-B 97, 109, 116 and 156; and HLA-C 6, 9, 11, 14, 21, 66, 77, 80, 95, 97, 99, 116, 156, 163 and 173. In all 13 had been previously reported by other investigators using classical biostatistical approaches. Using the same data set, traditional multivariate logistic regression identified only five amino acid substitutions associated with lower day 100 survival. Random forest analysis is a novel statistical methodology for analysis of HLA mismatching and outcome studies, capable of identifying important amino acid substitutions missed by other methods.
authors: Department of Pathology, University of Chicago Medical Center, Chicago, IL 60637-1470, USA. smarino@bsd.uchicago.edu
authors: S R
authors: SR
authors: Marino
authors: S
authors: S
authors: Lin
authors: M
authors: M
authors: Maiers
authors: M
authors: M
authors: Haagenson
authors: S
authors: S
authors: Spellman
authors: J P
authors: JP
authors: Klein
authors: T A
authors: TA
authors: Binkowski
authors: S J
authors: SJ
authors: Lee
authors: K
authors: K
authors: van Besien
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution / Q000276:immunology*; D003663:Decision Trees; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D011897:Random Allocation; D016019:Survival Analysis; D061349:Unrelated Donors
chemical_list: D015395:Histocompatibility Antigens Class I