Unbiased Gene Expression Analysis Implicates the huntingtin Polyglutamine Tract in Extra-mitochondrial Energy Metabolism (original) (raw)
Figure 2
HD CAG Mutation and 3-NP Treatment Produced Distinct Signatures
(A) Plot of unsupervised principal component analysis of triplicate datasets for wild-type striatal cells (ST7/7/), mutant striatal cells (ST111/111), and wild-type cells treated with 3-NP (ST7/7+3-NP), revealing discrete gene expression space for the HD CAG repeat (comparison of ST111/111 and ST7/7) and 3-NP treatment (comparison of ST7/7+3-NP and ST7/7).
(B) Dendrogram plot, generated by average linkage clustering algorithm analysis of the expression values of all probes, indicated proper clustering of triplicate samples within each group and revealed that the mutant cell group (ST111/111) was more closely related to the wild-type cell group (ST7/7) than to the 3-NP treated wild-type cell samples (ST7/7+3-NP). Arrows depict the data set comparisons to generate changes due to the HD CAG and 3-NP treatment.
(C) Diagram summarizing the identification of significantly altered probe signals using a stringent FDR _q_-value 0.005, which revealed 630 probes different between mutant and wild-type striatal cells (HD CAG) and 889 probes changed between wild-type cells and wild-type cells treated with 3-NP (3-NP), with 83 probes significant in both comparisons (shared). Of these, 70 % were concordantly changed.
(D) Plot of the correlation coefficients between the HD CAG- and 3-NP-changes for all probes (white), for the HD CAG significant probes (red), and for the 3-NP significant probes (green), demonstrating the distinct nature of the changes in the two comparisons.
(E) Volcano plots of fold-change versus FDR _q-_value for probes significant (q < 0.005) in the HD CAG comparison (red) and those same probes in the 3-NP comparison (green) (left panel) or the converse (right panel), showing the small overlap and more dynamic expression changes for the HD CAG repeat, compared to 3-NP treatment.