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Exploring brain transcriptomic patterns: a topological analysis using spatial expression networks

Characterizing the transcriptome architecture of the human brain is fundamental in gaining an understanding of brain function and disease. A number of recent studies have investigated patterns of brain gene expression obtained from an extensive anatomical coverage across the entire human brain using experimental data generated by the Allen Human Brain Atlas (AHBA) project. In this paper, we propose a new representation of a gene's transcription activity that explicitly captures the pattern of spatial co-expression across different anatomical brain regions. For each gene, we define a Spatial Expression Network (SEN), a network quantifying co-expression patterns amongst several anatomical locations. Network similarity measures are then employed to quantify the topological resemblance between pairs of SENs and identify naturally occurring clusters. Using network-theoretical measures, three large clusters have been detected featuring distinct topological properties. We then evaluate whether topological diversity of the SENs reflects significant differences in biological function through a gene ontology analysis. We report on evidence suggesting that one of the three SEN clusters consists of genes specifically involved in the nervous system, including genes related to brain disorders, while the remaining two clusters are representative of immunity, transcription and translation. These findings are consistent with previous studies showing that brain gene clusters are generally associated with one of these three major biological processes.