AI Article Synopsis

  • Cross-species differences can complicate translational research, making clinical trials less successful, and there's a need to better integrate this knowledge when interpreting animal model studies.
  • The Found In Translation (FIT) methodology uses public gene expression data to enhance the translation of mouse experiment results to human conditions, showing improved accuracy over traditional methods.
  • By applying FIT to 28 human diseases, researchers found that it not only predicted novel disease-associated genes, which were validated, but also increased the overlap of gene expression changes by 20-50%, helping to minimize false leads without additional experimental costs.

Article Abstract

Cross-species differences form barriers to translational research that ultimately hinder the success of clinical trials, yet knowledge of species differences has yet to be systematically incorporated in the interpretation of animal models. Here we present Found In Translation (FIT; http://www.mouse2man.org ), a statistical methodology that leverages public gene expression data to extrapolate the results of a new mouse experiment to expression changes in the equivalent human condition. We applied FIT to data from mouse models of 28 different human diseases and identified experimental conditions in which FIT predictions outperformed direct cross-species extrapolation from mouse results, increasing the overlap of differentially expressed genes by 20-50%. FIT predicted novel disease-associated genes, an example of which we validated experimentally. FIT highlights signals that may otherwise be missed and reduces false leads, with no experimental cost.

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http://dx.doi.org/10.1038/s41592-018-0214-9DOI Listing

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