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Bioinformatics Vol. 18 no. 8 2002
Pages 1054-1063
© 2002 Oxford University Press

Mapping physiological states from microarray expression measurements

Gregory Stephanopoulos *, Daehee Hwang , William A. Schmitt , Jatin Misra and George Stephanopoulos

Department of Chemical Engineering, Massachusetts Institute of Technology, Room 56--469, Cambridge MA 02139, USA

Received on July 12, 2001 ; revised on December 20, 2001 and February 22, 2002 ; accepted on February 18, 2002

Motivation: 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.

Contact: gregstep{at}mit.edu

* To whom correspondence should be addressed.


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