Fig. 1

Genomic profiling in the ProBio platform trial. Two 10-ml tubes of blood are drawn from each study participant and plasma is enriched. Extraction is performed to obtain cell-free DNA from plasma and germline DNA from white blood cells. Targeted sequencing is applied on both cell-free and germline DNA using the ProBio-panel. The ProBio panel covers mutations in 78 genes, structural variants in 11 genes and allows for interrogation of genome-wide copy-number alterations, microsatellite instability, and hypermutation. Sequence data is processed using an in-house developed bioinformatics infrastructure (https://autoseq-docs.readthedocs.io). All variants are manually examined to remove false positive calls. This information is condensed into a report which contains the biomarker profile for subsequent randomization of the study participants. Study participants that progress are reanalyzed and re-randomized