Abstract
Human brain development is a dramatic process composed of a series of complex and fine-tuned spatiotemporal gene expressions. A good comprehension of this process can assist us in developing the potential of our brain. However, we have only limited knowledge about the genes and gene functions that are involved in this biological process. Therefore, a substantial demand remains to discover new brain development-related genes and identify their biological functions. In this study, we aimed to discover new brain-development related genes by building a computational method. We referred to a series of computational methods used to discover new disease-related genes and developed a similar method. In this method, the shortest path algorithm was executed on a weighted graph that was constructed using protein-protein interactions. New candidate genes fell on at least one of the shortest paths connecting two known genes that are related to brain development. A randomization test was then adopted to filter positive discoveries. Of the final identified genes, several have been reported to be associated with brain development, indicating the effectiveness of the method, whereas several of the others may have potential roles in brain development.
Highlights
Beginning with the segregation of neural and glial cells from other types of tissues, brain development is a dramatic process composed of a series of complex and fine-tuned spatiotemporal gene expressions
We proposed a similar computational method to discover new candidate genes related to brain development
The discovery method was executed on the weighted graph G constructed in Section “Construction of the weighted graph based on protein-protein interactions”, which consisted of two stages: (I) execute the shortest path algorithm on G for finding new candidate genes and (II) construct a randomization test to filter these candidate genes
Summary
Beginning with the segregation of neural and glial cells from other types of tissues, brain development is a dramatic process composed of a series of complex and fine-tuned spatiotemporal gene expressions. These gene expressions contribute to brain transformation that involves both microscopic and macroscopic changes [1,2]. All mammalian embryos develop in a fundamentally similar way, human brains show more sophisticated neural structures and circuits than other species, which gives rise to human intelligence. Discovery of New Candidate Genes Related to Brain Development Understanding the PLOS ONE | DOI:10.1371/journal.pone.0118003 January 30, 2015
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