Using the P(active) metric, we find that most building blocks in the DEL have a low probability of resulting in active compounds. However, we also identify a small fraction of building blocks in each position with P(active) values significantly higher than average. Splitting building blocks into intervals based on their P(active) values, we find that the distribution of P(active) at every position is heavily rightskewed, with more than 95% of building blocks at every position having P(active) values less than 0.20 (Figure ). For positions 1 and 2, the top 1% of P(active) values are contained in the P(active) interval, [0.40, 0.60), whereas for position 3, the top 1% of P(active) values extends across the P(active) interval, [0.80, 1.00]. Given the mean P(active) value of all building blocks at each position is on the order of 10 -2 , this tells us that the top building blocks occur in active compounds at a rate about 50 times higher than average.