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METHODS AND GENE EXPRESSION SIGNATURE FOR ASSESSING RAS PATHWAY ACTIVITY

  • US 20100280987A1
  • Filed: 04/16/2010
  • Published: 11/04/2010
  • Est. Priority Date: 04/18/2009
  • Status: Abandoned Application
First Claim
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1. A method for predicting response of an human subject to an agent that modulates the RAS signaling pathway, said method comprising:

  • (a) classifying said human subject as having a deregulated or regulated RAS signaling pathway, wherein said classifying comprises;

    (i) calculating a measure of similarity between a first expression profile and a regulated RAS signaling pathway template, said first expression profile comprising the expression levels of a first plurality of genes in an isolated cell sample derived from said human subject, said regulated RAS signaling pathway template comprising expression levels of said first plurality of genes that are average expression levels of the respective genes in a plurality of human control cell samples not having at least one or more components of said RAS signaling pathway with abnormal activity, said first plurality of genes consisting of at least 5 of the genes for which biomarkers are listed in Tables 2a and 2b, wherein at least 1 gene of said 5 genes is selected from Table 2b;

    (ii) classifying said cell sample as having said regulated RAS signaling pathway if said first expression profile has a high similarity to said regulated RAS signaling pathway template, or classifying said cell sample as having said deregulated RAS signaling pathway if said first expression profile has a low similarity to said regulated RAS signaling pathway template;

    wherein said first expression profile has a high similarity to said regulated RAS signaling pathway template if the similarity to said regulated RAS signaling pathway template is above a predetermined threshold, or has a low similarity to said regulated RAS signaling pathway template if the similarity to said regulated RAS signaling pathway template is below said predetermined threshold; and

    (iii) displaying;

    or outputting to a user, user interface device, a computer readable storage medium, or a local or remote computer system;

    the classification produced by said classifying step (ii);

    wherein said human subject is predicted to respond to said agent if said cell sample is classified as having a deregulated RAS signaling pathway.

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