Title
Identification of optimal classification functions for biological sample and state discrimination from metabolic profiling data.
Abstract
Classification of biological samples for diagnostic purposes is a difficult task because of the many decisions involved on the number, type and functional manipulations of the input variables. This study presents a generally applicable strategy for systematic formulation of optimal diagnostic indexes. To this end, we develop a novel set of computational tools by integrating regression optimization, stepwise variable selection and cross-validation algorithms.The proposed discrimination methodology was applied to plasma and tissue (liver) metabolic profiling data describing the time progression of liver dysfunction in a rat model of acute hepatic failure generated by d-galactosamine (GalN) injection. From the plasma data, our methodology identified seven (out of a total of 23) metabolites, and the corresponding transform functions, as the best inputs to the optimal diagnostic index. This index showed better time resolution and increased noise robustness compared with an existing metabolic index, Fischer's BCAA/AAA molar ratio, as well as indexes generated using other commonly used discriminant analysis tools. Comparison of plasma and liver indexes found two consensus metabolites, lactate and glucose, which implicate glycolysis and/or gluconeogenesis in mediating the metabolic effects of GalN.
Year
DOI
Venue
2004
10.1093/bioinformatics/bth015
Bioinformatics
Keywords
Field
DocType
liver dysfunction,liver index,existing metabolic index,optimal diagnostic index,optimal classification function,consensus metabolites,diagnostic purpose,plasma data,biological sample,metabolic effect,state discrimination,better time resolution,metabolic profiling data,indexation,cross validation,variable selection,discriminant analysis
Data mining,Regression,Feature selection,Profiling (computer programming),Computer science,Metabolic clearance rate,Robustness (computer science),Computational biology,Linear discriminant analysis,Multivariate analysis,Statistics,Acute hepatic failure
Journal
Volume
Issue
ISSN
20
6
1367-4803
Citations 
PageRank 
References 
0
0.34
3
Authors
6
Name
Order
Citations
PageRank
Kyongbum Lee1707.40
Daehee Hwang26812.13
Tadaaki Yokoyama300.34
George Stephanopoulos410220.07
Gregory Stephanopoulos512413.54
Martin L Yarmush6315.26