Figure 1
Figure 1. In cis association between copy number and gene expression. (A) Frequency of gain and loss as a function of genomic position, calculated across all the serial FL samples from which DNA copy number were obtained (see supplemental Material and Methods). Colors indicate type of aberration, with red representing gains and green representing losses. (B) Pearson’s correlation coefficient as a function of genomic position (total base pairs) for all 21 461 genes. The genes marked in green have high cis-correlation (Pearson's r > 0.4) and differential gene expression in samples with loss vs samples with normal copy number (P < .05). The genes marked in red have high cis-correlation (Pearson's r > 0.4) and differential gene expression in samples with gain vs samples with normal copy number (P < .05). Further details about the selection of cis-genes are provided in the supplemental Material and Methods and in supplemental Figure 1. Correlations between copy number and gene expression were positively skewed in commonly aberrant genomic regions, indicating an influence of copy number on gene expression. (C) The molecular network most highly enriched with cis-genes. The network (denoted Network 1) was identified by using Ingenuity Systems Pathway Analysis with the Ingenuity Pathway Knowledge Database and specifying small network size. The NFκB transcription factor plays the role as a hub in this network, and 14 genes in the network encode regulators and signaling molecules upstream of the NFκB transcription factor: BTK, FASTKD1, IGBP1, IKBKG, IRAK1, MAP3K7, PPP4R1, ROCK1, TAB2, TBK1, TMED7-TICAM2, TRIM37, TSCD22, and USP11. The genes/molecules colored red and green in Network 1 represent cis-genes located in regions of gain and loss, respectively. The color intensity increases with increasing frequency of the respective genomic aberration (as shown in supplemental Figure 6).

In cis association between copy number and gene expression. (A) Frequency of gain and loss as a function of genomic position, calculated across all the serial FL samples from which DNA copy number were obtained (see supplemental Material and Methods). Colors indicate type of aberration, with red representing gains and green representing losses. (B) Pearson’s correlation coefficient as a function of genomic position (total base pairs) for all 21 461 genes. The genes marked in green have high cis-correlation (Pearson's r > 0.4) and differential gene expression in samples with loss vs samples with normal copy number (P < .05). The genes marked in red have high cis-correlation (Pearson's r > 0.4) and differential gene expression in samples with gain vs samples with normal copy number (P < .05). Further details about the selection of cis-genes are provided in the supplemental Material and Methods and in supplemental Figure 1. Correlations between copy number and gene expression were positively skewed in commonly aberrant genomic regions, indicating an influence of copy number on gene expression. (C) The molecular network most highly enriched with cis-genes. The network (denoted Network 1) was identified by using Ingenuity Systems Pathway Analysis with the Ingenuity Pathway Knowledge Database and specifying small network size. The NFκB transcription factor plays the role as a hub in this network, and 14 genes in the network encode regulators and signaling molecules upstream of the NFκB transcription factor: BTK, FASTKD1, IGBP1, IKBKG, IRAK1, MAP3K7, PPP4R1, ROCK1, TAB2, TBK1, TMED7-TICAM2, TRIM37, TSCD22, and USP11. The genes/molecules colored red and green in Network 1 represent cis-genes located in regions of gain and loss, respectively. The color intensity increases with increasing frequency of the respective genomic aberration (as shown in supplemental Figure 6).

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