Figure 2
Figure 2. Identifying potential WM-associated variants and prioritization of potential WM genes. (A) Differential expression analysis between WM tumor cells and their normal counterparts using a public data set (GSE12668). The significantly differentially expressed genes are plotted in light blue, with an adjusted P value cutoff of 1% and 2-fold change; nonsignificant genes are shown in gray. (B) Genes containing potential WM variants were prioritized with use of GRAIL coupled with coexpression networks. The significant ones (adjusted P values of 5%) are shown. Genomic positions (POS; GRCh37) as well as complementary DNA (cDNA) and protein changes are listed. Deleteriousness of a variant was predicted by PolyPhen2 either as benign (B), damaging (D), or possibly damaging (P). CHROM, chromosome. (C) Gene prioritization, with use of coexpression networks and tissue specificity in B cells. GRAIL was used to assess the significance of functional relatedness; adjusted P values are shown in log10 scale. The mean tissue specificity score for each gene was calculated as the average of its tissue specificity scores across different B-cell samples in the GEP database. Two genes with the highest functional significance and highest tissue specificity scores in B cells are indicated. Genes containing B, D, and P variants are shown in red, green, and blue, respectively. Adjusted P values are shown for LAPTM5 and HCLS1. (D) Box plots comparing LAPTM5 and HCLS1 mRNA expression across cancer types that were deposited in the TCGA. Normalized counts were obtained using RNA-Seq by Expectation Maximization (RSEM) software. The left and right ends of the boxes represent the 25th and 75th percentile values, respectively, and the segment in the middle is the median. The left and right extremes of the bars extend to the minimum and maximum values.

Identifying potential WM-associated variants and prioritization of potential WM genes. (A) Differential expression analysis between WM tumor cells and their normal counterparts using a public data set (GSE12668). The significantly differentially expressed genes are plotted in light blue, with an adjusted P value cutoff of 1% and 2-fold change; nonsignificant genes are shown in gray. (B) Genes containing potential WM variants were prioritized with use of GRAIL coupled with coexpression networks. The significant ones (adjusted P values of 5%) are shown. Genomic positions (POS; GRCh37) as well as complementary DNA (cDNA) and protein changes are listed. Deleteriousness of a variant was predicted by PolyPhen2 either as benign (B), damaging (D), or possibly damaging (P). CHROM, chromosome. (C) Gene prioritization, with use of coexpression networks and tissue specificity in B cells. GRAIL was used to assess the significance of functional relatedness; adjusted P values are shown in log10 scale. The mean tissue specificity score for each gene was calculated as the average of its tissue specificity scores across different B-cell samples in the GEP database. Two genes with the highest functional significance and highest tissue specificity scores in B cells are indicated. Genes containing B, D, and P variants are shown in red, green, and blue, respectively. Adjusted P values are shown for LAPTM5 and HCLS1. (D) Box plots comparing LAPTM5 and HCLS1 mRNA expression across cancer types that were deposited in the TCGA. Normalized counts were obtained using RNA-Seq by Expectation Maximization (RSEM) software. The left and right ends of the boxes represent the 25th and 75th percentile values, respectively, and the segment in the middle is the median. The left and right extremes of the bars extend to the minimum and maximum values.

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