Exagen Diagnostics, Inc., all rights reserved Biomarker Discovery in Genomic Data with Partial Clinical Annotation Cole Harris, Noushin Ghaffari.

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Exagen Diagnostics, Inc., all rights reserved Biomarker Discovery in Genomic Data with Partial Clinical Annotation Cole Harris, Noushin Ghaffari

July 13, 2006 Exagen Confidential & Proprietary Public microarray data Status –Data has been collected from a large number of samples Breast cancer – 158 datasets in GEO repository but –Majority of data does not have associated clinical information to support clinically relevant biomarker discovery Breast cancer prognosis – 22 datasets in GEO repository Why? –Difficult and expensive to obtain For prognostic marker discovery, long term follow-up is required. For drug response marker discovery, patient response is required.

July 13, 2006 Exagen Confidential & Proprietary Our approach: –Map data across platforms to common gene set –Within common genes, subsets of genes scored with objective function containing terms for: Accuracy in clinically annotated datasets –Crossvalidation, bootstrap Clustering in datasets lacking annotation –Inter-cluster vs. intra-cluster distance But still under development –Intrinsic assumptions violated? under what circumstances? –Optimal objective function? simple approach? information based approach? Concurrent mining approach

July 13, 2006 Exagen Confidential & Proprietary Synthetic data example 2 datasets: –Annotated: 100 features across 40 samples (20X2 classes) –Unannotated: 100 features across 60 samples –10 informative features IDs annotated samples held out as test set (10X2 classes) GA search across 5-feature markers –Baseline: LOOCV KNN (1nn) on annotated training data –Concurrent: LOOCV KNN (1nn) K-MEANS (ncl=2) distance between clusters/average cluster spread - error in expected cluster proportions

July 13, 2006 Exagen Confidential & Proprietary ALL/AML diagnosis Data sources –Annotated: Golub TR, et al. Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science Oct 15;286(5439): –Unannotated: Armstrong SA, et al. MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia. Nat Genet Jan;30(1):41-7. Annotated data –Train – 38 samples (27 ALL, 11 AML) –Test – 34 samples (20 ALL, 14 AML) –7129 genes Unannotated data –52 samples (24 ALL, 28 AML) –12,600 genes 6002 genes in common GA search across 3-gene markers –Baseline: LDA on annotated training data –Concurrent: LDA K-MEANS (ncl=2) distance between clusters/average cluster spread - error in expected cluster proportions Baseline – Top 200 Concurrent – Top 200 LDA accuracy on test set

July 13, 2006 Exagen Confidential & Proprietary Thank you for your attention Questions?