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. 2019 Mar 18;116(14):6868–6877. doi: 10.1073/pnas.1811028116

Fig. 5.

Fig. 5.

PTEN R159 methylation is involved in regulation of pre-mRNA splicing. (A) Quantification of differentially expressed alternative splicing events in three pairwise comparisons (PTEN vs. control, PTEN R159K vs. PTEN, and PTEN R159K vs. control). A5SS or A3SS, alternative 5′ or 3′ splice site; MXE, mutually exclusive exons; RI, retained introns; SE, skipped exons. Significant events are listed in Datasets S1–S3. (B) Intersections of alternative splicing events among three pairwise comparisons (Left) containing 18 combinatorial modes of change, as listed in Right. Alternative splicing events in 6 of the 18 combinatorial modes account for about 96% of all intersected events and can be categorized into three regulatory modes, including those which are regulated by PTEN in a methylation-related manner (majority in yellow), a methylation-unrelated manner (majority in pink), or a nonmethylation dominant negative manner (majority in cyan). The IncLevelDifference index is important for understanding pairwise comparison, intersection analysis, and the related datasets. When the expression level of the inclusive form of a splicing event in X group is higher or lower than in Y group, then the IncLevelDifference index is, respectively, >0 (+) or <0 (−) in pairwise comparison of X vs. Y. For example, the regulatory pattern of methylation-related includes two conditions: (i) The expression level of the inclusive form of a splicing event is higher in the PTEN group, compared with the control group or PTEN R159K group. In this condition, the splicing event does not show a significant difference in pairwise comparison of PTEN R159K vs. control, the IncLevelDifference index is “+” in pairwise comparison of PTEN vs. control, and is “−” in pairwise comparison of PTEN R159K vs. PTEN. (ii) The expression level of the inclusive form of a splicing event is lower in the PTEN group, compared with the control or PTEN R159K group. In this condition, the splicing event does not show a significant difference in pairwise comparison of PTEN R159K vs. control, the IncLevelDifference index is “−” in pairwise comparison of PTEN vs. control and is “+” in pairwise comparison of PTEN R159K vs. PTEN. (C) Heatmap showing pairwise gene coexpression matrices for 220 known or putative splicing factors in normal brain tissues and tissues adjacent to GBM (Left), PTEN-proficient GBM (Center), and PTEN-deficient GBM (Right).