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Integrated molecular imaging reveals tissue heterogeneity driving host-pathogen interactions.


Cassat| Moore| Wilson| Stark| Prentice| Van de Plas| Perry| Zhang| Virostko| Colvin| Rose| Judd| Reyzer| Spraggins| Grunenwald| Gore| Caprioli| Skaar JE| JL| KJ| Z| BM| R| WJ| Y| J| DC| KL| AM| ML| JM| CM| JC| RM| EP , . Science translational medicine. 2018 3 14; 10(432).


Diseases are characterized by distinct changes in tissue molecular distribution. Molecular analysis of intact tissues traditionally requires preexisting knowledge of, and reagents for, the targets of interest. Conversely, label-free discovery of disease-associated tissue analytes requires destructive processing for downstream identification platforms. Tissue-based analyses therefore sacrifice discovery to gain spatial distribution of known targets or sacrifice tissue architecture for discovery of unknown targets. To overcome these obstacles, we developed a multimodality imaging platform for discovery-based molecular histology. We apply this platform to a model of disseminated infection triggered by the pathogen , leading to the discovery of infection-associated alterations in the distribution and abundance of proteins and elements in tissue in mice. These data provide an unbiased, three-dimensional analysis of how disease affects the molecular architecture of complex tissues, enable culture-free diagnosis of infection through imaging-based detection of bacterial and host analytes, and reveal molecular heterogeneity at the host-pathogen interface.

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