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Activity Number: 34
Type: Contributed
Date/Time: Sunday, July 29, 2012 : 2:00 PM to 3:50 PM
Sponsor: Biometrics Section
Abstract - #306211
Title: General Quality Assessment Metrics for Whole-Genome Gene Expression Profiling by Illumina's DASL Assay
Author(s): Douglas Mahoney*+ and Terry M. Therneau and S. Keith Anderson and Jin Jen and Jean-Pierre A. Kocher and Monica Reinholz and Edith A. Perez and Jeanette E. Eckel-Passow
Companies: Mayo Clinic and Mayo Clinic and Mayo Clinic and Mayo Clinic and Mayo Clinic and Ventana Medical Systems, Inc. and Mayo Clinic and Mayo Clinic
Address: 201 1st Street SW, Rochester, MN, 55905, United States
Keywords: Gene Expression Profiling ; Normalization ; Illumina ; cDNA-mediated Annealing Selection extension and Ligation Assay ; DASL ; Quality Assessment

Many institutions have large archives of paraffin embedded tissue that provide a unique opportunity for understanding genomic signatures of disease, but have been relatively untouched by high dimensional platforms due to RNA degradation. Recently, Illumina introduced their cDNA-mediated Annealing Selection extension and Ligation (DASL) assay that is specifically designed to combat RNA degradation and is used in conjunction with their bead array technology. Normalization of expression values presents particular challenges as these data are noisy and skewed due to differential sample degradation raising two concerns; whether a highly skewed array should be included in down stream analyses and whether outlier arrays can be reliably identified. We introduce two metrics that measure the stress an array undergoes during normalization and how much an array deviates from the remaining arrays post normalization. These metrics are applied to a study of 1,618 formalin-fixed, paraffin-embedded HER2-positive breast cancer samples from the N9831 adjuvant trial processed with the DASL assay. We show that these metrics are useful for scrutinizing the expression data and identifying suspect arrays.

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