GradientScanSurv—An exhaustive association test method for gene expression data with censored survival outcome

Accurate assessment of the association between continuous variables such as gene expression and survival is a critical aspect of precision medicine. In this report, we provide a review of some of the available survival analysis and validation tools by referencing published studies that have utilized these tools. We have identified pitfalls associated with the assumptions inherent in those applications that have the potential to impact scientific research through their potential bias. In order to overcome these pitfalls, we have developed a novel method that enables the logrank test method to handle continuous variables that comprehensively evaluates survival association with derived aggregate statistics. This is accomplished by exhaustively considering all the cutpoints across the full expression gradient. Direct side-by-side comparisons, global ROC analysis, and evaluation of the ability to capture relevant biological themes based on current understanding of RAS biology all demonstrated that the new method shows better consistency between multiple datasets of the same disease, better reproducibility and robustness, and better detection power to uncover biological relevance within the selected datasets over the available survival analysis methods on univariate gene expression and penalized linear model-based methods.