Joint classification and subtype discovery in tumor diagnosis by gene expression profiling

1. A computer readable medium embodying a program of instructions executable by a processor to perform method steps for classification of biological tissue by gene expression profiling, the method steps comprising:

providing a training set of gene expression profiles of known tissue samples;

constructing a probabilistic boosting tree classifier using a learning framework, the framework for learning models for discriminating between two-classes, the models automatically being assembled as the probabilistic boosting tree classifier comprising a plurality of nodes, in which each node is a strong classifier combined from a plurality of weak classifiers based on boosting; and

outputting the probabilistic boosting tree classifier for tissue sample classification.

2. The computer readable medium of claim 1 , wherein outputting the probabilistic boosting tree classifier comprises storing the probabilistic boosting tree classifier on a computer-readable media.

3. The computer readable medium of claim 1 , further comprising:

applying the probabilistic boosting tree classifier to a gene expression profile of a tissue of interest; and

outputting a classification of the tissue of interest.

4. The computer readable medium of claim 3 , wherein outputting the classification comprises one of displaying the classification and storing the classification in a computer-readable media.

5. The computer readable medium of claim 3 , wherein outputting the classification comprises outputting disease subtypes discovered automatically.

6. The computer readable medium of claim 1 , further comprising:

determining an overall approximated posterior distribution of a gene expression profile of a tissue sample of interest; and

outputting a classification of the tissue sample of interest.

7. The computer readable medium of claim 1 , wherein the training set is one of a gene expression profile and a protein expression profile.

8. A computer readable medium embodying a program of instructions executable by a processor to perform method steps for a multi-way classification of biological tissue by gene expression profiling for a multi-class diagnosis problem, the method steps comprising:

providing a training set of expression profiles of known tissue samples; and

determining an empirical distribution of the training set;

determining a plurality of histograms of the training set for a plurality of features;

determining a feature of the plurality of features that reaches a minimum of entropy of the histograms and dividing the multi-class diagnosis problem into two-classes; and

determining a probabilistic boosting tree classifier according to a two-class probabilistic tree procedure applied to the training set, wherein the probabilistic boosting tree classifier is stored on a computer-readable media.

9. The computer readable medium of claim 8 , wherein the training set is one of a gene expression profile and a protein expression profile.

10. The computer readable medium of claim 8 , further comprising:

applying the probabilistic boosting tree classifier against a gene expression profile of a tissue of interest; and

outputting a classification of the tissue of interest.

11. The computer readable medium of claim 10 , wherein outputting the classification comprises one of displaying the classification and storing the classification in a computer-readable media.

12. The computer readable medium of claim 10 , wherein outputting the classification comprises outputting a disease subtype of the tissue of interest.

13. The computer readable medium of claim 8 , wherein the probabilistic boosting tree classifier is applied to determine an overall approximated posterior distribution of a gene expression profile of a tissue of interest, the method further comprising outputting a classification of the tissue of interest.

14. A computer-implemented method for classification of biological tissue by gene expression profiling comprising:

a computer to implement the steps of:

providing a training set of gene expression profiles of known tissue samples;

learning a first-layer strong classifier of the known tissue samples by combining weak classifiers by boosting; creating two sample sets based on the first-layer classifier;

populating the two sample sets by creating a next layer of classifiers based on a previous layer classifier;

organizing the classifiers in a tree data structure; and

outputting the tree data structure as a probabilistic boosting tree classifier for tissue classification and disease subtype discovery.

15. The computer-implemented method of claim 14 , wherein outputting the probabilistic boosting tree classifier comprises storing the probabilistic boosting tree classifier on a computer-readable media.

16. The computer-implemented method of claim 14 , further comprising:

applying the probabilistic boosting tree classifier against a gene expression profile of a tissue of interest; and

outputting a classification of the tissue of interest.

17. The computer-implemented method of claim 16 , wherein outputting the classification comprises one of displaying the classification and storing the classification in a computer-readable media.

18. The computer-implemented method of claim 16 , wherein outputting the classification comprises outputting a disease subtype.

19. The computer-implemented method of claim 14 , the method further comprising:

determining an overall approximated posterior distribution of a gene expression profile of a tissue of interest; and

outputting a classification of the tissue of interest.