Modulation of hot spot nucleation specificity by global aggregation propensity. The black solid line represents a standard amyloidogenic protein aggregation profile, with only one "hot spot" and low global aggregation propensity. The pink discontinuous line corresponds to a typical aggregation profile from an inclusion-body-forming protein, with many "hot spots" and high global aggregation propensity. The horizontal lines represent the aggregation-propensity average thresholds for each sequence. The coloured regions indicate the area of each "hot spot" over the aggregation propensity threshold. It is proposed that a higher area over the threshold promotes a more specific aggregation reaction, resulting in highly ordered deposits.