Top, number of bucket-assigned (white bars with a black contouring line) and GIE-positive (pink bars with pink contouring line) samples across 20 evenly distributed TMB buckets using the entire cohort (n = 6,319). Bottom, representation of observed (pink) and simulated (gray) GIE frequency across these buckets. For the observed GIE values, the average (represented as pink dots) and s.d. (vertical error bars and shaded pink area) values are computed using 1,000 bootstraps from the total number of samples classified into each bucket (from the top panel). For the simulated GIE values, average (gray triangle) and s.d. (vertical bars and shaded gray area) values are computed from 100 GIE simulations using the total number of samples assigned into each bucket.