1. Immuno-Assay (Proteomic and Metabonomic)
Global Discovery
Proteomics
Metabonomics
Table 1
Frontal Cortex
Hippocampus
Frontal Cortex
Hippocampus
11 Del vs 10 Control
11 Del vs 10 Control
Cohort 1
Cohort 2
Cohort 1
Two-Phase Extraction
Two-Phase Extraction
11 Del vs 10 Control
13 Del vs 13 Control
11 Del vs 10 Control
Cohort 1 & 2
combined
Aqueous Phase
Aqueous Phase
Total lysis protein extraction
Total lysis protein extraction
20 Del vs 21 Control
Total lysis protein extraction
LC MS/MS
LC MS/MS
In-gel digestion
Acetone precipitation
Acetone precipitation
Acetone precipitation
Immuno-Assay (Proteomic and Metabonomic)
Reduction
Reduction
Reduction
Serum
Alkylation
Alkylation
Alkylation
Tryptic digestion
11 Del vs 10 Control
Tryptic digestion
Tryptic digestion
Multiplex-Immunoassay
Label-free LC MSE
Label-free LC MSE
Label-free LC MSE
Label-free LC MSE
PLGS + Elucidator
PLGS + Elucidator
PLGS + Elucidator
PLGS + Elucidator
Transcriptomics
Frontal Cortex
Hippocampus
Peptide detected in both replicates and >80 samples
Peptide detected in both replicates and >80 samples
Peptide detected in both replicates and >80 samples
Peptide detected in both replicates and >80 samples
Fenelon et al.,2013
Stark et al.,2008
Stark et al.,2008
10 Del vs 10 Control
10 Del vs 10 Control
10 Del vs 10 Control
Affymetrix
Gene 1.1 ST Array plates 
Affymetrix GeneChip (MOE430AB – 45K probes)
Affymetrix GeneChip (MOE430AB – 45K probes)
MSstats
MSstats
MSstats
MSstats
Results - Cross Comparison
Figure 1A+D
578 proteins:
59 (FDR p*<0.05)
715 proteins:
186 (FDR p*<0.05)
552 proteins:
104 (FDR p*<0.05)
570 proteins
104 (FDR p*<0.05)
52 probe sets significant (FDR, p*<0.05)
2,087 probe sets significant (FDR, p*<0.05)
455 probe sets significant (FDR, p*<0.05)
Figure 2: GSEA and Figure 1C: IPA
WGCNA:
Chromatin assembly, RNA processing, Protein localization, Glycosylation,
GO-EA: Oxidative phosphorylation, ATP-synthesis electron transport
GO-EA: synaptic transmission, network with DLG4, CAMK2 as node
Pathway analysis
GO-EA + IPA
Pathway analysis
GO-EA + IPA
Pathway analysis
GO-EA + IPA
Pathway analysis
GO-EA + IPA
Targeted Proteomic Validation (SRM)
Frontal Cortex and Hippocampus (20 Del vs 20 Control)
Table 2
22q11.2 encoded proteins
miRNA targets
(Global Discovery derived)
Differentially regulated proteins (Global discovery derived)
Glutamatergic signalling
(Transcriptomic HPC network-based)
ASD & mental retardation associated proteins
Hippocampal network proteins
Total lysis protein extraction
Acetone precipitation
Reduction
Alkylation
Tryptic digestion
Label-free LC MSE
Data Analysis
Pathway Model
Figure 3
Legend: GO-EA = Gene ontology enrichment analysis, WGCNA = weighted-gene coexpression network analysis, IPA = ingenuity pathway analysis