A cross-species analysis method to analyze animal models' similarity to human's disease state

Shuhao Yu,Xuan Li,Chunyan Li,Lulu Zheng,Yixue Li,Pei Hao,Yun Li,Chenchen Ma

doi:10.1186/1752-0509-6-s3-s18

Abstract

BackgroundAnimal models are indispensable tools in studying the cause of human diseases and searching for the treatments. The scientific value of an animal model depends on the accurate mimicry of human diseases. The primary goal of the current study was to develop a cross-species method by using the animal models' expression data to evaluate the similarity to human diseases' and assess drug molecules' efficiency in drug research. Therefore, we hoped to reveal that it is feasible and useful to compare gene expression profiles across species in the studies of pathology, toxicology, drug repositioning, and drug action mechanism.ResultsWe developed a cross-species analysis method to analyze animal models' similarity to human diseases and effectiveness in drug research by utilizing the existing animal gene expression data in the public database, and mined some meaningful information to help drug research, such as potential drug candidates, possible drug repositioning, side effects and analysis in pharmacology. New animal models could be evaluated by our method before they are used in drug discovery.We applied the method to several cases of known animal model expression profiles and obtained some useful information to help drug research. We found that trichostatin A and some other HDACs could have very similar response across cell lines and species at gene expression level. Mouse hypoxia model could accurately mimic the human hypoxia, while mouse diabetes drug model might have some limitation. The transgenic mouse of Alzheimer was a useful model and we deeply analyzed the biological mechanisms of some drugs in this case. In addition, all the cases could provide some ideas for drug discovery and drug repositioning.ConclusionsWe developed a new cross-species gene expression module comparison method to use animal models' expression data to analyse the effectiveness of animal models in drug research. Moreover, through data integration, our method could be applied for drug research, such as potential drug candidates, possible drug repositioning, side effects and information about pharmacology.

Highlights

Animal models are indispensable tools in studying the cause of human diseases and searching for the treatments
In view of the above information, we proposed a novel approach to assess whether the animal models recapitulate the essential features of human diseases for drug research
We found that trichostatin A and some other HDACs could have very similar response across cell lines and species at gene expression level

Summary

Introduction

Animal models are indispensable tools in studying the cause of human diseases and searching for the treatments. The scientific value of an animal model depends on the accurate mimicry of human diseases. The primary goal of the current study was to develop a cross-species method by using the animal models’ expression data to evaluate the similarity to human diseases’ and assess drug molecules’ efficiency in drug research. Despite the advantages in employing animal models to study various human diseases, it has still been a challenging task in drug research to test thousands of compounds in animal models for searching a few promising candidates. Thence, we cannot directly test IL-8 antagonists or agonists in murine systems [11] In this regard, the scientific value of an animal model depends on how accurately it can mimic the human disease, and an assessment of the animal models’ similarity to human disease state is requisite

Objectives

Methods

Results

Discussion

Conclusion