The simulation data are generated using WES data taken from (1) 12 MBC and 6 CRPC patients and (2) 8 NSCLC patients. Each patient has an early plasma sample (Blood T1), a WBC sample (WBC), and a late plasma sample (Blood T2). The three WES datasets from a patient are used directly or mixed to generate the simulation samples. To simulate the scenario of monitoring a patient for MRD or cancer recurrence, each case contains three simulation samples: a pre-treatment plasma sample, a pre-treatment WBC sample, and a post-treatment plasma sample. The raw data from Blood T1 are used directly as the pre-treatment plasma sample for all cases. WBC and Blood T2 are mixed at specified dilutions to simulate the post-treatment plasma sample. To simulate remission cases, we generate two independent random samplings from the raw WBC data to use as the pre-treatment WBC sample and the post-treatment plasma sample. To simulate the emergence of second primary cancers, each case contains two simulation samples: a pre-treatment WBC sample and a post-treatment plasma sample. The generation of simulation samples for second primary cancer monitoring is the same as for MRD/recurrence monitoring, except that the pre-treatment plasma sample (Blood T1) is not used.