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Table 1.

Pathway groupings and pathway-pathway interactions.

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Fig 1.

Pathway groupings.

Pathways were grouped into subsets of two classes. Pathways in the Disease class are surrounded by a black border; the remainder of the pie chart sections are in the Functional class. Labels indicate pathway groupings (number of pathways in grouping/percentage of total number of pathways).

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Fig 1 Expand

Table 2.

Enrichment analyses for gene ontologies.

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Table 2 Expand

Fig 2.

ASD pathway network.

Pathways are grouped vertically under two classes, Disease and Function. The color of each node within the groupings represents the p-value of that pathway. The size of each node represents the number of ASD genes in that pathway. Interactions between pairs of pathways are indicated by edges. The pathway-pathway interaction matrix is in S3 Table.

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Fig 2 Expand

Table 3.

Involvement of ASD genes in the ASD pathway network.

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Table 3 Expand

Fig 3.

Integrated MAPK and calcium signaling in ASDs.

a. Overlapping genes in calcium and MAPK signaling pathways. b. The voltage-gated calcium channel mediates the influx of Ca2+, which modulates PKC and Ras. Growth factors bind to the extracellular domain of receptor tyrosine kinases (RTKs), and signal molecules Grb2 (growth factor receptor-bound protein 2) and Sos (son of sevenless) are consequently recruited to the internal docking site, resulting in Ras activation. Ras triggers a phosphorylation cascade including Raf and MEK. This leads to ERK activation and translocation to the nucleus, where ERK then activates transcription factors that mediate gene expression. The ASD genes are listed in light blue frames close to the corresponding gene products that are shown in orange.

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Fig 3 Expand

Table 4.

ASD genes in the pathway neuroactive ligand-receptor interaction.

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Table 4 Expand

Fig 4.

A systematic biological framework.

The flow chart in a, summarizes the analyses and related results. The conclusions are visualized into a cellular model in b. The relationship between genes, gene products, environmental information processing and phenotypes is schematized in c.

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