“Systems Approach” for Integrating Autism Study Data Yields Unique Insights

“Systems Approach” for Integrating Autism Study Data Yields Unique Insights

Posted: March 24, 2015

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Studies of the genetic underpinnings of autism spectrum disorder (ASD) have so far pointed to more than 300 potentially relevant gene mutations. A team at Stanford University School of Medicine reasons that a complete picture of the biological causes of ASD may require integrating several different kinds of research data. In a paper published online December 30th in Molecular Systems Biology, the team reported on a preliminary effort to do just that.

The Stanford scientists included Alexander E. Urban, Ph.D., a 2012 NARSAD Young Investigator grantee and Joachim F. Hallmayer, M.D., a 1991 Young Investigator grantee. The paper’s lead and senior authors were, respectively, Jingjing Li, Ph.D., and Michael P. Snyder, Ph.D. With their colleagues, they created a matrix of several types of data obtained from affected and unaffected individuals: genome sequencing data (which identifies mutations); data about the expression of genes (how active or inactive particular genes are); and data indicating how large numbers of proteins encoded by these and other genes interact within complex networks.

The data on proteins––13,039 different proteins, forming networks encompassing 69,113 potential interactions––led to the identification of 817 “modules” comprised only of proteins that interacted mainly with each other. Two of these “highly interacting” modules were enriched for proteins known from previous analyses to be mutated in ASD. One module has 1,430 genes and controls the regulation of gene transcription; the other has 119 genes and controls the transmission of signals across synapses, or gaps between neurons. The team chose to focus on the latter module because it was substantially more enriched for genes known to be involved in ASD.

Some of this module’s genes were expressed throughout the brain, some with particular frequency in a part of the brain called the corpus callosum. The corpus callosum plays a central role in handling signaling traffic across the brain’s two hemispheres. Its main components are axons––the long-range “wires” that connect brain cells––and a cell type called oligodendrocyte, which gives rise to the myelin sheathing that insulates axons, just as rubber coating insulates electrical wires. “Our study provides a molecular clue to the reduced size of the corpus callosum that has been observed in people with ASD,” the team noted.

“Different from previous research, our study illustrates the role of oligodendrocytes in ASD, which myelinate and support the axons of the corpus callosum in interhemispheric signal transmission,” they said. The team says its results make the case for future study of the role of oligodendrocytes and other cell types in ASD pathology.

Read the abstract.