Additional file 4 of Systematic interrogation of mutation groupings reveals divergent downstream expression programs within key cancer genes

Additional file 4: Figure S3. Clustering subgrouping model coefficients reveals structure of mutation heterogeneity. We applied hierarchical clustering to examine the average regression model gene coefficients across all forty cross-validation folds for each of our subgrouping tasks. Subgroupings with task AUCs of below 0.7 were omitted, as were genes that did not have an absolute model coefficient ranked in the top five for any of the remaining tasks. Distances between subgroupings were computed by taking the inverse of the Spearman correlation across all gene coefficients; these were then used to cluster subgroupings into five groups. To facilitate presentation, here we only show these clusterings for subgroupings which did not have another subgrouping in the same cluster with a higher AUC and a Jaccard index of at least 0.9 with respect to the subgroupings’ mutated samples. The subgroupings with the highest AUC in each cluster are bolded, as is the gene-wide task. An asterisk is placed next to the AUCs of subgroupings with cv-significantly better performance than that of the gene-wide task. We include here these heatmaps for GATA3, TP53, and PIK3CA in METABRIC-(LumA) as well as KRAS in TCGA-LUAD. The corresponding figures for the remaining cases can be found at our data portal under Figures/S3 - Gene Coefficient Heatmaps. The names of these figures have the format (expr-source)__(cohort)__(gene)_auto-heatmap_Ridge.svg.

补充文件4：图S3。基于聚类亚组模型系数揭示突变异质性结构。我们针对每项亚组分析任务，对全部40次交叉验证折的回归模型基因系数平均值开展层级聚类分析。我们剔除了任务曲线下面积（Area Under Curve，AUC）低于0.7的亚组，同时剔除了在其余任一任务中模型系数绝对值未进入前五的基因。亚组间的距离通过所有基因系数的斯皮尔曼（Spearman）相关系数的倒数计算得出，基于该距离将亚组聚类为5个组别。为便于可视化展示，本文仅呈现符合以下条件的亚组聚类结果：该亚组所在的同一聚类簇中，不存在其他亚组具有更高的AUC，且与该亚组的突变样本的杰卡德（Jaccard）指数至少为0.9。每个聚类簇中AUC最高的亚组以及全基因任务均以粗体标注。在交叉验证中表现显著优于全基因任务的亚组的AUC旁会标注星号。本次展示的热图包含METABRIC-(LumA)队列中GATA3、TP53、PIK3CA以及TCGA-LUAD队列中KRAS的相关结果。其余案例的对应图表可在我们的数据门户的Figures/S3 - Gene Coefficient Heatmaps栏目中获取。此类图表的命名格式为：(expr-source)__(cohort)__(gene)_auto-heatmap_Ridge.svg。