We then sought to quantitatively examine whether beam-induced diffraction changes arose from correlated, rather than random, changes in specific subsets of Bragg reflections. To achieve this, the intensity of each reflection was tracked as a function of fluence, and k-means clustering employed to classify reflections based on when in the diffraction series they were maximally excited, as illustrated for representative cases in Figure . Crystals of Co(II)-porphyrin showed only minor, non-correlated fluctuations in intensity of individual Bragg reflections, attributable to measurement error or noise, with minimal overall decay evident across the time scales of these experiments (Fig. ). In contrast, dramatic changes in diffraction associated with crystals of Zn(II)-methionine were a consequence of abrupt and correlated changes in large sets of reflections. These abrupt events occurred in all crystals of Zn(II)-methionine measured at room temperature, always following the accumulation of 0.07 -0.1 e -/Å 2 fluence. For some Zn(II)methionine crystals, nearly all initially observed reflections disappeared, yielding an entirely new set of Bragg reflections (Fig. ). All crystals surveyed exhibited diffraction changes between these two extremes. For example, crystals of Zn(II)-histidine showed gradual correlated changes in intensity of Bragg reflections, concomitant with a slow decay in overall signal (Fig ). In dose series from crystals of biotin and Cu(II)-serine, moderate fluctuations in intensities were often accompanied by the gradual appearance of clusters of reflections, and disappearance of others, in response to electron beam exposure. These correlated changes consistently marked the early phases of global decay in reflection intensities (Fig ).