Science Spotlight: Assessing biological meaning of transcriptional changes from microarray data

This month’s featured publication shows how IPA can be used to tease out the biological meaning of the many transcriptional changes revealed by microarray data. Dr. Jianchun Xiao and team from Johns Hopkins used IPA to explain some of the variation of the neurobiological effects of different strains of Toxoplasma on infected individuals.

“The tropism of Toxoplasma gondii for brain has been linked with specific behavioral changes and psychosis in humans. Most infecting-Toxoplasma organisms fall into 1 of 3 canonical lineages which differ in the capacity to induce pathology or occurrence in humans and animals.  The goal of our study was to investigate the particular ways these Toxoplasma genotypes differ in their interactions with host cells.  One gene/protein may have many roles, but biological interpretation of the many transcriptional changes revealed by microarray data is vastly more difficult.  We relied on IPA to tease out the potential biological meaning of those alterations.  Importantly, IPA enabled us to conclude that the three lineages differ in the ability to manipulate their host, e.g. they employ different strategies to avoid, deflect, or subvert host defense mechanisms.  IPA convinced us, and hopefully our readers, that strain type is one of the key factors in determining the outcome of Toxoplasma infection.  Understanding the differential effects caused by these strains could enable predicting the outcome of infection and point out directions to be explored in future studies to eliminate transmission or cure disease.”

-Jianchun Xiao, Ph.D.
Johns Hopkins School of Medicine
Research Fellow at the Stanley Division of Developmental Neurovirology

Differential Effects of Three Canonical Toxoplasma Strains on Gene Expression in Human Neuroepithelial Cells

Infect. Immun. 2010 Dec 13.  Xiao J, Jones-Brando L, Talbot CC Jr, Yolken RH; The Stanley Division of Developmental Neurovirology, Institute for Basic Biomedical Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA

This month, we feature a study from Johns Hopkins School of Medicine that examined the transcriptional profile of human neuroepithelioma cells in response to three different strains of Toxoplasma.  The extent of the gene expression changes varied considerably among the three strains. Neuroepithelial cells infected with Toxoplasma type I exhibited the highest level of differential gene expression, whereas type II infected cells had a substantially smaller number of genes which were differentially expressed. Cells infected with type III exhibited intermediate effects on gene expression. The three strains also differed in the individual genes and gene pathways which were altered following cellular infection. For example, gene ontology (GO) analysis indicated that type I infection largely affects genes related to central nervous system while type III infection largely alters genes which affect nucleotide metabolism; type II infection does not alter expression of a clearly defined set of genes.  Analysis with IPA suggested the three lineages differ in the ability to manipulate their host, e.g. they employ different strategies to avoid, deflect, or subvert host defense mechanisms. These observed differences may explain some of the variation in the neurobiological effects of different strains of Toxoplasma on infected individuals.

To read the full article, go to http://iai.asm.org/cgi/reprint/IAI.00947-10v1?view=long&pmid=21149591

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