Extended Data Fig. 1: Quality Control Metrics.

a. Sequence quality metrics for mutation calls across participants and time-points filtered for 2% VAF. Plotted are the AO (the number of sequenced reads supporting the alternative allele (mutation)) against the UAO (the number of sequenced reads with unique start sites that support the alternative allele - a measure of molecular complexity). Red dotted lines denote filter thresholds in both measurements (AO ≥ 5, UAO ≥ 3) and points are scaled by the VAF of the somatic mutation. Only 7 (of 275) data points failed to meet our filter criteria which were not excluded as they were supported with matching events across any participants’ time series. b. Box and jitter plot of the variant allele frequency of all observed events in the 1st Wave at 2% VAF coloured by variant classification and ordered by largest mean VAF showing the median and interquartile range. c. The 95% MDAF (Minimal Detectable Allele Fraction with 95% Confidence) versus the VAF for each event. All variants used in our analysis above 2% VAF are scaled by their clone size and coloured by their functional consequence. Points in red are events that failed to pass our quality criteria and are removed from subsequent work. d. The VAF Outlier P-Value (describing the pan-cohort position-specific background noise) versus VAF for each event. All variants used in the analysis above 2% VAF are scaled by their clone size and coloured by their functional consequence. Points in red are events that failed to pass our quality criteria and are removed from subsequent work. All accepted events that exceed VAF Outlier P-Value > 0.1 are generally low VAF and are supported by matching events across the time-series that adhere to our acceptance criteria of VAF Outlier P-Value ≤ 0.1. e. Schematic of all affected genes in the cohort with the largest clone size of an event in any given gene shown above 2% VAF. All affected participants have been clustered across all time-points, with the point size scaled by VAF and coloured by the functional consequence of the variant (as per legend).