In this work, gene expression in autism spectrum disorder (ASD) is analyzed with the goal of selecting the most attributed genes and performing classification. The objective was achieved by utilizing a combination of various statistical filters and a wrapper-based geometric binary particle swarm optimization-support vector machine (GBPSO-SVM) algorithm. The utilization of different filters was accentuated by incorporating a mean and median ratio criterion to remove very similar genes. The results showed that the most discriminative genes that were identified in the first and last selection steps included the presence of a repetitive gene (CAPS2), which was assigned as the gene most highly related to ASD risk. The merged gene subset that was selected by the GBPSO-SVM algorithm was able to enhance the classification accuracy.
Ankrd11 is a potential chromatin regulator implicated in neural development and autism spectrum disorder (ASD) with no known function in the brain. Here, we show that knockdown of Ankrd11 in developing murine or human cortical neural precursors caused decreased proliferation, reduced neurogenesis, and aberrant neuronal positioning. Similar cellular phenotypes and aberrant ASD-like behaviors were observed in Yoda mice carrying a point mutation in the Ankrd11 HDAC-binding domain. Consistent with a role for Ankrd11 in histone acetylation, Ankrd11 was associated with chromatin and colocalized with HDAC3, and expression and histone acetylation of Ankrd11 target genes were altered in Yoda neural precursors. Moreover, the Ankrd11 knockdown-mediated decrease in precursor proliferation was rescued by inhibiting histone acetyltransferase activity or expressing HDAC3. Thus, Ankrd11 is a crucial chromatin regulator that controls histone acetylation and gene expression during neural development, thereby providing a likely explanation for its association with cognitive dysfunction and ASD.