PenDA, a rank-based method for personalized differential analysis: Application to lung cancer

摘要

The hopes of precision medicine rely on our capacity to measure individual molecular information for personalized diagnosis and treatment. These challenging perspectives will be only possible with the development of efficient methodological tools to identify patient-specific molecular defects from the many precise molecular information that one can access at the single-individual, single tissue or even single-cell levels. Such methods will provide a better understanding of disease-specific biological mechanisms and will promote the development of personalized therapeutic strategies. Here we describe a novel method, named PenDA, to perform differential analysis of gene expression at the individual level. Based on a realistic benchmark of simulated tumors, we demonstrated that PenDA reaches very high efficiency in detecting sample-specific deregulated genes. We then applied the method to two large cohorts associated with lung cancer. A detailed statistical analysis of the results allowed to isolate genes with specific deregulation patterns, like genes that are up-regulated in all tumors or genes that are expressed but never deregulated in any tumors. Given their specificities, these genes are likely to be of interest in therapeutic research. In particular, we were able to identified 37 new biomarkers associated to bad prognosis that we validated on two independent cohorts.