Detailed description of each component.

Detailed description of each component.</p

Fig 3 -

A. The measured distance traveled (blue) and velocity (red) by a single mouse wheel over the course of 50 hours for four mice in one cage. Yellow and blue panels indicate the light-dark cycle throughout the study period B. Measured distance traveled for four mice in individual cages over the course of 50 hours. Upon inspection during take down of the system, Cage 4 appeared to have inhibited the wheel with bedding at some point during the first night, so rotations of the wheel were not possible, and thus the tracker ceased measurements.</p

A bill of materials for constructing the tracker system.

A bill of materials for constructing the tracker system.</p

Fig 4 -

A. Distance traveled overnight by each cage prior to caloric restriction. B. Distance traveled overnight by the same cages following three days of caloric restriction at 80% of the normal diet. C. Comparison of total distance before and after caloric restriction. When Cage 5 was removed from the analysis, the difference between baseline and caloric restriction was not found to be statistically significant (permutation test, p = 0.0876).</p

Fig 2 -

A. Top: The measured distance traveled by the mouse wheel over the course of 85 seconds for five sensors at once. B. Bottom: Average velocity of the mouse wheel with a small (4) averaging window.</p

Fig 1 -

A. The magnet attached to the wheel and hut. B. The Hall effect sensor, connected via wires to the Arduino. A red LED indicates when the sensor detects a magnet. C. The 3D-printed housing for the Arduino and breadboard, with wires for six sensors leaving the enclosure. D. Aligning and connecting the Hall effect sensor to overlap the rotation path of the magnet inside the cage. E. Example of the system connected to 6 cages. The wires are all leading back to the Arduino, which is connected via USB to a laptop.</p

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

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