Table 4.
Functional profiling of genes altered in nine-month-old transgenic α-syn mice.
| GO annotation term | % of regulated genes | p value |
|---|---|---|
| protein binding | 28.94% | 6.81E-06 |
| regulation of biological process | 25.11% | 3.05E-05 |
| regulation of cellular process | 21.70% | 8.93E-04 |
| regulation of metabolism | 17.02% | 0.0013 |
| regulation of physiological process | 21.28% | 0.0013 |
| transcriptional activator activity | 3.40% | 0.0014 |
| biopolymer modification | 12.77% | 0.0018 |
| regulation of cellular physiological process | 20.43% | 0.0018 |
| transcription regulator activity | 10.21% | 0.0021 |
| cytoskeletal protein binding | 4.68% | 0.0022 |
| DNA binding | 13.62% | 0.0026 |
| intracellular signaling cascade | 8.94% | 0.0031 |
| biopolymer metabolism | 17.45% | 0.0034 |
| transcription factor activity | 8.09% | 0.0035 |
| regulation of transcription | 14.89% | 0.0039 |
| protein modification | 11.91% | 0.0044 |
| zinc ion binding | 12.34% | 0.0044 |
| binding | 48.09% | 0.0045 |
| regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolism | 14.89% | 0.0047 |
| transcription | 14.89% | 0.0064 |
| regulation of transcription, DNA-dependent | 14.04% | 0.0064 |
| regulation of cellular metabolism | 15.32% | 0.0076 |
| transcription, DNA-dependent | 14.04% | 0.0082 |
| cellular physiological process | 48.94% | 0.0099 |
| cellular process | 54.47% | 0.012 |
| enzyme linked receptor protein signaling pathway | 3.40% | 0.015 |
| nucleic acid binding | 17.87% | 0.017 |
| ubiquitin cycle | 4.68% | 0.021 |
| GTPase regulator activity | 3.40% | 0.021 |
| transition metal ion binding | 13.19% | 0.025 |
| primary metabolism | 34.47% | 0.026 |
| protein amino acid phosphorylation | 5.53% | 0.027 |
| nucleobase, nucleoside, nucleotide and nucleic acid metabolism | 18.30% | 0.029 |
| macromolecule metabolism | 22.55% | 0.035 |
| negative regulation of biological process | 6.38% | 0.039 |
| signal transduction | 14.47% | 0.040 |
| enzyme regulator activity | 5.11% | 0.040 |
| negative regulation of cellular process | 5.96% | 0.043 |
| cell communication | 15.32% | 0.043 |
To determine functional categories associated with α-syn overexpression, we used the DAVID 2007 functional annotation tool (http://david.abcc.ncifcrf.gov/home.jsp), which classifies each probe into one or more functional categories using annotations from over 40 ontological databases and then determines which functional categories are represented in the data set more frequently than expected by chance alone. We limited the functional annotation chart generated by DAVID by classification of genes to functional categories defined by Gene Ontology Database annotations. Only probes with a q value ≤20% were used for the ontology analysis. We considered significant those categories with a p value ≤0.05 and contained at least 3% of the regulated genes. All molecular function and biological process annotation terms that fulfilled these criteria were included in the table regardless of how broad or narrow the annotation was. Therefore, we included broad categories, such as “binding,” as well as more specific and informative categories, such as “zinc ion binding.” The website QuickGO (http://www.ebi.ac.uk/ego) describes the GO annotation categories with their meanings and hierarchical relationships.