Mapping physiological states from microarray expression measurements.
BACKGROUND
The increasing use of DNA microarrays to probe cell physiology requires methods for visualizing different expression phenotypes and explicitly connecting individual genes to discriminating expression features. Such methods should be robust and maintain biological interpretability.


RESULTS
We propose a method for the mapping of the physiological state of cells and tissues from multidimensional expression data such as those obtained with DNA microarrays. The method uses Fisher discriminant analysis to create a linear projection of gene expression measurements that maximizes the separation of different sample classes. Relative to other typical classification methods, this method provides insights into the discriminating characteristics of expression measurements in terms of the contribution of individual genes to the definition of distinct physiological states. This projection method also facilitates visualization of classification results in a reduced dimensional space. Examples from four different cases demonstrate the ability of the method to produce well-separated groups in the projection space and to identify important genes for defining physiological states. The method can be augmented to also include data from the proteomic and metabolic phenotypes and can be useful in disease diagnosis, drug screening and bioprocessing applications.
Stephanopoulos
Gregory
G
Department of Chemical Engineering, Massachusetts Institute of Technology, Room 56-469, Cambridge 02139, USA. gregstep@mit.edu
Hwang
Daehee
D
Schmitt
William A
WA
Misra
Jatin
J
Stephanopoulos
George
G
D000465:Algorithms; D016000:Cluster Analysis; D000458:Cyanobacteria / Q000235:genetics / Q000502:physiology; D004247:DNA / Q000032:analysis / Q000145:classification* / Q000235:genetics / Q000502:physiology*; D030541:Databases, Genetic; D016002:Discriminant Analysis; D015870:Gene Expression / Q000235:genetics / Q000502:physiology*; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D008954:Models, Biological; D015233:Models, Statistical; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000503:physiopathology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D011786:Quality Control; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D004247:DNA