Interactive neuroinflammation pathways and transcriptomics-based identification of drugs and chemical compounds for schizophrenia

Figures & data

Table 1. Clinical and demographic characteristics of GSE92874 subjects.

Subject ID	Sex	Ethnicity	Age at biopsy (y)	Age of onset (y)	Phenotype	Family history
Control_s1	M	Caucasian	0	–	–	Unknown
Control_s2	M	Caucasian	20	–	–	Unknown
Control_s3	F	Caucasian	20	–	–	Unknown
Control_s4	F	Caucasian	25	–	–	Unknown
Schiz_s1	M	Caucasian	22	6	Suicide	Unknown
Schiz_s2	M	Caucasian Jewish/Scandinavian	26	Unknown	Episodes of agitation, delusions of persecution and fear of assassination; at age four mild features of pervasive developmental disorder	Father and sister affected, brother autistic at age four
Schiz_s3	F	Caucasian Jewish	27	Unknown	Drug abuse; Schizo-affective disorder	Father and brother affected
Schiz_s4	M	Caucasian Jewish	23	15	Paralogical thinking, affective shielding, splitting of affect from content, and suspiciousness	Affected father, anorexic/schizoid sister

The table was adapted from Narla et al. (2017). Subject characterisation and RNA sequencing were performed by Brennand et al. (2011).

Figure 1. Gene ontology (GO) subnetwork of developmental biological processes. The subnetwork was created using BiNGO functional overrepresentation analysis, and filtering for GO terms with a false discovery rate adjusted p-value (q-value) below .01. The blue colour gradient indicates the significance of the enrichment, with darker colours corresponding to smaller q-values. Node sizes indicate the number of direct interactions (degree) as determined in the original network.

Figure 2. Neuroinflammation and glutamatergic signalling. (www.WikiPathways.org/instance/WP5083) The colours indicate the differential expression of mRNA SCZ vs. healthy control according to the dataset by Narla et al. (2017). Log2 fold change values are reported, with red and blue representing upregulation and downregulation, respectively. Green indicates a false discovery rate adjusted p-value (q-value) < .05.

Figure 3. Complement system in neuronal development and plasticity. (http://www.WikiPathways.org/instance/WP5090). The colours indicate the differential expression of mRNA SCZ vs. healthy control according to the dataset by Narla et al. (2017). Log2 fold change values are reported, with red and blue representing upregulation and downregulation, respectively. Green indicates a false discovery rate adjusted p-value (q-value) < .05.

Figure 4. Network of interactions between FDA approved drugs and their targets in the combined neuroinflammation and complement system network. (A) Interactions derived from WikiPathways:WP5083 network. (B) Interactions derived from WikiPathways:WP5090 network. Log2 fold change values of the genes (ellipse) are represented by a colour gradient, with red and blue indicating upregulation and downregulation, respectively. DEGs are signified by a white label and black border. FDA approved drugs (grey diamonds) targeting the genes are categorised into antipsychotics (green), immunosuppressants (red), anaesthetics (purple), CNS depressants (grey), anticonvulsants (yellow) and antiplatelet (orange).

Figure 5. Network of interactions between DEGs and the 15 most significantly enriched WikiPathways pathways. Pathways (rounded rectangles) with the highest pathway statistics-determined Z-scores and their first neighbour DEGs that were upregulated (red) or downregulated (blue).

Narla ST, Lee YW, Benson CA, Sarder P, Brennand KJ, Stachowiak EK, Stachowiak MK. 2017. Common developmental genome deprogramming in schizophrenia – Role of integrative nuclear FGFR1 signaling (INFS). Schizophr Res. 185:17–32. doi: 10.1016/j.schres.2016.12.012.

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