Reagent sets and gene signatures for renal tubule injury

Abstract

The invention discloses reagent sets and gene signatures for predicting onset of renal tubule injury in a subject. The invention also provides a necessary set of 186 genes useful for generating signatures of varying size and performance capable of predicting onset of renal tubule injury. The invention also provides methods, apparatuses and reagents useful for predicting future renal tubule injury based on expression levels of genes in the signatures. In one particular embodiment the invention provides a method for predict whether a compound will induce renal tubule injury using gene expression data from sub-acute treatments.

1 . A reagent set for testing whether renal tubule injury will occur in a test subject comprising a plurality of polynucleotides or polypeptides representing a plurality of genes selected from Table 4.  
     
     
         2 . The reagent set of  claim 1 , wherein the plurality of genes is the set of genes in any one of iterations 1 through 5 in Table 4.  
     
     
         3 . The reagent set of  claim 1 , wherein the plurality of genes are selected from a linear classifier capable of classifying renal tubule injury with a training log odds ratio of greater than or equal to 4.35.  
     
     
         4 . The reagent set of  claim 1 , wherein the plurality of genes includes at least 4 genes having at least 2% of the total impact of all of the genes in Table 4.  
     
     
         5 . The reagent set of  claim 1 , wherein the plurality of genes includes at least 8 genes having at least 4% of the total impact of the genes in Table 4.  
     
     
         6 . The reagent set of  claim 1 , wherein the reagents are polynucleotide probes capable of hybridizing to the plurality of genes selected from Table 4.  
     
     
         7 . The reagent set of  claim 6 , wherein the polynucleotide probes are primers for amplification of the plurality of genes.  
     
     
         8 . The reagent set of  claim 6 , wherein the polynucleotide probes are immobilized on one or more solid surfaces.  
     
     
         9 . The reagent set of  claim 1 , wherein the reagents are polypeptides that bind to a plurality of proteins encoded by the plurality of genes selected from Table 4.  
     
     
         10 . The reagent set of  claim 9 , wherein the proteins are secreted proteins.  
     
     
         11 . An apparatus for predicting whether renal tubule injury will occur in a test subject comprising a reagent set according to  claim 1 .  
     
     
         12 . The apparatus of  claim 11 , wherein the reagents are polynucleotides.  
     
     
         13 . The apparatus of  claim 11 , wherein the reagents are polypeptides.  
     
     
         14 . A set of genes useful for testing whether a compound will induce renal tubule injury comprising a random selection of at least about 10% of the genes from Table 4, wherein the addition of said randomly selected genes to a fully depleted gene set for the renal tubule injury classification question increases the average logodds ratio of the linear classifiers generated by the depleted set to at least about 2.5.  
     
     
         15 . The set of  claim 14 , wherein the randomly selected percentage of genes from the necessary set is at least 20% and the average logodds ratio is increased to at least about 3.3.  
     
     
         16 . The set of  claim 14 , wherein the randomly selected percentage of genes from the necessary set is at least 40% and the average logodds ratio is increased to at least about 4.0.  
     
     
         17 . A reagent set for classifying renal tubule injury comprising a set of polynucleotides or polypeptides representing a plurality of genes selected from Table 4, wherein the addition of a random selection of at least 10% of said plurality of genes to the fully depleted set for the renal tubule injury classification question increases the average logodds ratio of the linear classifiers generated by the depleted set by at least 2-fold.  
     
     
         18 . The reagent set of  claim 17 , wherein the random selection is of at least 40% of said plurality of genes and the average logodds ratio of the linear classifiers generated by the depleted set by at least 3-fold.  
     
     
         19 . An apparatus comprising a set of polynucleotides capable of specifically binding to the reagent set of  claim 17.