Figure 1.

Genealogical proteomics of 22q11.2 pedigrees fibroblasts using quantitative mass spectrometry. Human pedigrees of a control family (A) and families where one of the subjects is affected by 22q11.2 microdeletion syndrome and early childhood psychosis (A, E, G, blue numbers). Experimental design is designated at the top left corner of dot plots (B, F, H). For example, B shows a TMT experiment where proteomes from probands 1 and 2 were compared against unaffected individuals, Subjects 3, 11–16. C, Hierarchical clustering analysis of the proteome in Subjects 1–3 and 11–16. Euclidian distance clustering of columns and rows (4264 TMT protein quantitations) shows segregation of related family members. D, Dot plot of proteins encoded within the 22q11.2 chromosomal segment quantitated in TMT Experiment B. Asterisks denote significant differences p = 0.04146 to p < 0.0001, t test. B, F, H, Depictions of all mass spectrometry quantifications where the color code denotes individuals being compared (blue symbols are proteins whose expression is changed, gray symbols are unaffected proteins). Significant protein expression changes for: TMT and SILAC were considered to be >2 or <0.5, whereas in LFQ a −log(p) value threshold of 1.3 was used. I, The Venn diagram summarizes proteins with significant expression changes in B, F, and H. Asterisk denotes proteins whose expression changed in all patients. Bold font depicts proteins encoded within the 22q11.2 segment. Blue color fonts are proteins contained in the human Mitocarta 2.0 dataset. Individual MS/MS data can be found in Figure 1-2. Ontological comparisons among pedigrees and proteomic platforms can be found in Figure 1-1, and Figure 1-3.