Figure 1.
Unsupervised Hierarchical cluster of differences between BRCAX samples with or without a BRCA1 or BRCA2 sequence variant of Low Clinical Significance.
Unsupervised cluster analysis was performed using 1778 genes that varied in expression 2-fold from the mean in 10% of BRCAX without a BRCA1/2 LCS variant and BRCAX samples with an LCS. The tree structure at the top of the cluster shows how related the samples are to each other. The majority of BRCAX samples without an LCS (black) clustered in a distinct group away from BRCAX with an LCS variant (red).
Figure 2.
Unsupervised Hierarchical Cluster of Differences between BRCA1, BRCA2 and BRCAX samples.
Clustering was based on 4751 genes which varied 2-fold difference in gene expression in at least 10% of samples. There are two main clusters, the BRCAX samples without a BRCA1/2 LCS variant (black) cluster to the right, whereas BRCA1 (green), BRCA2 (blue) and BRCAX samples with a BRCA1/2 LCS variant (red) are predominantly located in the left cluster. The missense pathogenic mutations of BRCA1 or BRCA2 are indicated with arrows and 6/9 cluster closest to the BRCAX LCLs.
Table 1.
Accuracy of Prediction of Mutation Status using a Gaussian Process Classifier*
Figure 3.
Venn Diagrams of Differences between BRCA1 or BRCA2 and BRCAX LCLs with or without a LCS.
T-tests (p-value<0.05) were performed to determine genes that differed between LCLs as follows: A) BRCA1 Truncating mutations vs BRCAX with no LCS, and BRCA1 missense mutations vs BRCAX with no LCS; B) BRCA1 Truncating mutations vs BRCAX with an LCS, and BRCA1 missense mutations vs BRCAX with an LCS. C) BRCA2 Truncating mutations vs BRCAX with no LCS, and BRCA2 missense mutations vs BRCAX with no LCS; D) BRCA2 Truncating mutations vs BRCAX with an LCS, and BRCA1 missense mutations vs BRCAX with an LCS. For each comparison, the overlap of genes is shown.
Table 2.
Mutation Prediction of BRCA1 and BRCAX samples based on SVM
Table 3.
Mutation Prediction of BRCA2 and BRCAX samples based on SVM
Figure 4.
Confidence of Predictions for Missense BRCA1 LCLs as Determined by Distance from the SVM Plane.
The SVM plane separating BRCA1 from BRCAX is shown by the red line. If the sample falls over the line (black point) the missense mutation is correctly predicted as pathogenic for BRCA1 mutation. If the sample falls under the line (red point) the missense mutation is incorrectly predicted as BRCAX. The gene lists used for the predictions are the top 200 genes from BRCA1 missense vs BRCAX, and the top 200 genes from BRCA1 Truncating vs BRCAX.