Distribution of 1000 resamplings of the mean pN/ mean pS ratio of the genes involved in ASD (yellow), comorbid disorders within the ASD cluster (red) and other comorbid disorders (blue).

The different panels show comparisons between: genes associated with ASD only (yellow) versus all other comorbid disorders (red+blue) (Panel A), genes associated with ASD only (yellow) versus comorbid disorders within the ASD cluster (red) (Panel B), genes associated with ASD and comorbid within the cluster (yellow + red) versus the genes outside the cluster (blue) (Panel C), genes associated with ASD only (yellow) versus genes associated with ASD outside the ASD cluster (blue) (Panel D).</p

Network analysis of the KEGG Orthologs and the pathways with which they are associated in the KEGG database.

<p>Each node in the inner circle represents a KEGG Ortholog and each node in the outer circle indicates the pathway in which each KO is involved. The size of each node is proportional to its connectivity.</p

Boxplot of the dN/dS ratio calculated from the alignment of 9 primates including human, chimpanzee, gorilla, orangutan, gibbon, macaque, baboon, marmoset and bushbaby.

<p>The results of the Mann Whitney test showed that genes involved in several comorbid disorders have undergone more purifying selection than the genes uniquely associated with ASD. This observation is consistent with the GERP results in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0157937#pone.0157937.g004" target="_blank">Fig 4</a>.</p

Analysis using KEGG database of the pathways associated with: 1) all the genes involved in ASD, 2) the genes involved in ASD only and 3) the pathways associated with ASD and no other comorbid disorders.

<p>The percent indicates the number of KEGG Orthologs detected with this analysis in comparison to the total number of KEGG Orthologs of this pathway, i.e. the percentage of the pathway covered in this analysis. For 1) and 2) we show only the top 15 pathways.</p

Boxplot showing the length of nucleotide sequence under constraint (using Genomic Evolutionary Rate Profiling) normalized by the total length of each set.

<p>A Mann Whitney test was used to test if the genes involved in ASD alone have undergone more purifying selection than the gene involved in comorbid disorders.</p

Hierarchical cluster analysis using the presence/absence matrix of genes associated with Autism Spectrum Disorders (ASD) and disorders comorbid to autism (complete list provided in S5 Table).

<p>Values at branches are <i>p</i>-values (in red) and bootstrap probabilities (blue) in percentage, and the clusters framed in red are supported by a <i>p</i>-value of 0.15. This approach revealed several clusters of disorders based on the genes they share with each other, including one cluster with ASD and five other disorders.</p