Performance comparison and parameter optimization.

<p>(A) Different pipelines show different sensitivity and specificity. Varying DoC and VAF thresholds in the variant calling process has an additional affect on the predictions in terms of sensitivity and specificity, respectively. Each pipeline is represented with a different symbol and the performance of each pipeline (in terms of sensitivity and specificity) is plotted under varying DoC and VAF thresholds. Note that the X-axis represents the false positive rate (1-specificity). In this ROC plot, the closer the point to the upper left point of the graph, the better the sensitivity and the specificity. Different colors of the symbols indicate the performance of the pipeline under changing VAF thresholds, and the two shaded boxes indicate the performance under changing DoC thresholds. The plot shows that (i) decreasing the DoC threshold increases the sensitivity of all pipelines as indicated with the blue dotted line; (ii) increasing the VAF threshold increases the specificity with a slight decrease in sensitivity as indicated (in the example of BLAT+VarScan pipeline) with the red dotted line; (iii) the BWA-SW+SSAHA2+Atlas-SNP2 pipeline has the best performance among all pipelines under DoC = 3 & VAF = 0.20 thresholds as indicated with the yellow arrow. The Roche pipeline is indicated with a black diamond shape since no parameter changes were performed on it, and SSAHA2+SAMTools and BWA-SW+SAMTools pipelines were colored grey since no VAF threshold changes were performed on them. (B) The Matthews correlation coefficient for each pipeline is shown for the most optimal performance of that pipeline (<b><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0038463#pone.0038463.s005" target="_blank">Table S1</a></b>). It is interesting to note that the optimal performance of all the pipelines, except Roche gsMapper, was observed for a DoC threshold of 3.