Using bioinformatics to validate mouse models of human disease

26 August 2015

Bioinformatics

Francis Crick Institute scientists have validated a mouse model of a human disease called melioidosis, using bioinformatics to confirm that many of the same molecular biological processes occur in mice as humans.

The work has also provided some new insights into this often severe infection, for which there is currently no vaccine and which can be difficult to treat with antibiotics.

Melioidosis can present in many different ways in humans - from acute blood poisoning, with  death rates of up to 40%,  to chronic localised infection or even dormant disease. It is caused by a bacteria that is found in tropical locations, particularly in SE Asia and Northern Australia, but is being increasingly reported in other tropical countries. It  is spread through direct contact with contaminated water and soil and people with diabetes in these countries are particularly at risk of infection.

Dr O'Garra (currently based at Mill Hill) said: "Mouse models have been widely used to study infections and to test new therapies or vaccines. However in human melioidosis it's not known how faithfully such mouse models of the disease mimic its biology at a molecular level."

In this study the team compared all the genes over or under-expressed in tissue and blood samples from mice as a result of infection with B. pseudomallei, the bacteria that causes melioidosis. They compared this to the blood gene expression profiles of patients with acute melioidosis in North East Thailand.

The results showed that the blood gene expression profile in mice infected with B. pseudomallei accurately reflects the disease severity in animals with latent, acute and chronic infections and showed strong similarities among key host immune defence processes to those observed in human patients.

Dr O'Garra said: "Our data not only provide new information on the disease process of this infection but also demonstrate that a complementary set of bioinformatics approaches can provide valuable insights into the response pathways that are similar in mice and humans.

"This approach can therefore be used to validate mouse models of human disease and lead to ways to improve these."

The paper, The Blood Transcriptome of Experimental Melioidosis Reflects Disease Severity and Shows Considerable Similarity with the Human Disease, is published in the Journal of Immunology.

  • Scientists have validated a mouse model of a human disease called melioidosis, showing that many of the same molecular biological processes occur in mice as humans. The work has also improved understanding of this often severe infection.
  • The research was carried out by scientists from the Francis Crick Institute, the London School of Hygiene & Tropical Medicine, the University of Surrey in Guildford, Khon Kaen University in Thailand, and the Baylor Institute for Immunology Research in Texas, USA. It was supported by the Medical Research Council and the European Research Council.