Panel Informativity Optimizer An R Package to Improve Cancer Next-Generation Sequencing Panel Informativity

Mutation detection by next-generation sequencing is routinely used for cancer diagnosis. Selecting an optimal set of genes for a given cancer is not trivial as it has to optimize informativity (ie, the number of patients with at least one mutation in the panel), while minimizing panel length to reduce sequencing costs and increase sensitivity. We propose herein Panel Informativity Optimizer (PIO), an open-source software developed as an R package with a user-friendly graphical interface to help optimize cancer next-generation sequencing panel informativity. Using patient-level mutational data from either private data sets or preloaded data set of 91 independent cohorts from 31 different cancer types, PIO selects an optimal set of genomic intervals to maximize informativity and panel size in a given cancer type. Different options are offered, such as the definition of genomic intervals at the gene or exon level and the use of optimization strategy at the patient or patient per kilobase level. PIO can also propose an optimal set of genomic intervals to increase informativity of custom panels. A panel tester function is also available for panel benchmarking. Using public databases, as well as data from real-life settings, we demonstrate that PIO allows panel size reduction of up to 1000 kb, and accurately predicts the performance of custom or commercial panels. (J Mol Diagn 2022, 24: 697e709; https:// doi.org/10.1016/j.jmoldx.2022.03.005)