Integrative statistical analysis pipeline for RNA-seq and NanoString with application to gene expression data of cancer patients Jeea Choi, Catarina D.

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Integrative statistical analysis pipeline for RNA-seq and NanoString with application to gene expression data of cancer patients Jeea Choi, Catarina D. Campbell, Xiaoshan Wang, Wei He, Leary Rebecca, Venkatesan Kavitha, Doug Robinson, Stephane Wong, Bin Fu, Ying A. Wang July 31, 2018

RNAexpressionToolbox Motivation Gene expression profiling enables a wide variety of basic research, translational medicine, and in vitro diagnostics applications Many variations of statistical methods for RNA-seq and NanoString have been published with application to cancer genomics RNAexpressionToolbox We implemented comprehensive analyses steps for both RNA- seq and NanoString analysis into a R package We applied the pipeline to both RNA-seq and NanoString expression data from commercial samples of 38 melanoma cancer patients and 28 non-small cell lung cancer (NSCLC) patients Business Use Only

Application to Melanoma, NSCLC Figure 1: Concordance between RNA-seq and NanoString of one sample (left) and distribution of correlation coefficient (right) displayed. Melanoma data Normalization RNA-seq normalization by TMM (Robinson, et al.,2010) NanoString normalization by NanoStringNorm (Waggott et al., 2012) High concordance between assays (Fig. 1) Sensitive Detection of Expressed Genes (Fig. 2) Similar proportion of genes had detectable expression with low level threshold cutoff 34 (4.5%) 684 (90.8%) 22 (2.9%) 13 (1.7%) not detected by either Detection threshold ≥ 1 counts (mean) 123 (18.8%) 448 (59.5%) 46 (6.1%) 136 (18.1%) not detected by either Detection threshold ≥ 50 counts (mean) RNA-seq NanoString RNA-seq NanoString Figure 2: Genes detected by RNA-seq and NanoString Panels Business Use Only

Application to Melanoma, NSCLC Lung Figure 3: Top 50 DE genes in immune response genes (GO:0006955) are shown in RNA-seq panel DE analysis (edgeR) has performed using RNA-seq between Melanoma and NSCLC samples Total 5,666 DE genes were identified (FDR 1%) Out of 495 genes in immune response GO term (GO:0006955), 72 (41) % are contained in the RNA-seq (NanoString) panel Top DE genes in immune response GO term are shown in both panels Melanoma Lung Figure 4: Top 24 out of 50 DE genes found in NanoString panel are shown Business Use Only