Introduction 1 2 3 4 6 7 8 http://www.ICDNS.org 6 9 11 12 14 15 16 17 Materials and methods Data set used http://www.ncbi.nlm.nih.gov/projects/geo 3 7 8 10 18 Data analysis procedures employed http://www.vmware.com 4 10 p Hierarchical clustering was executed on both rows and columns using ArrayAssist 5.5 (Pearson centred distance metric, centroid linkage rule). Similarity images were produced to visualise the quality of clustering results (SI_Figure_1). In addition, self-organising map clustering was performed on both rows and columns using a Euclidean distance metric in ArrayAssist 5.5 (maximum number of iterations 50, number of grid rows 3, number of grid columns 4, initial learning rate 0.03, initial neighbourhood radius 5, grid topology hexagonal, neighbourhood type bubble). the find common targets algorithm build pathway tool cell process filter option diseases entity type 19 8 http://www.ncbi.nlm.nih.gov/sites/entrez Results The extended set of 892 PD priority genes p 3 20 1 http://www.affymetrix.com/analysis/index.affx http://www.pdgene.org/ Fig. 1 left right red black green  Gene ontology and pathway analysis of the differentially expressed genes 2 Fig. 2 a in silico P b In silico  3 Fig. 3 violet green red grey and/or broken lines Blue shading 2  4 4 5 Fig. 4 11  Fig. 5 marked yellow red blue  21 Relationship to diseases and drug interactions 2 22 23 ‘Hub’ vs ‘peripheral’ genes 2 24 25 1 Table 1 Up-regulated ‘peripheral’ priority genes  Discussion 24 26 27 28 29 30 31 32 33 37 38 26 39 http://www.neurogenetics.net/Multidimensional.html 7 8 40 41 http://www.alzforum.org/new/detailprint.asp?id=1688 42 43 44 The view that the 892 nigral genes presented here are relevant for sporadic PD is supported by the finding that their pattern of expression is characteristic of nervous tissue (SI_Figure_2). It is further clear from our data that the human substantia nigra in PD does not represent dead tissue but that there is an active ongoing disease process understanding of which may hold the key to halting PD. The dysregulated priority genes may reside at the core of the disease process and could serve as novel targets for therapeutic intervention. This idea is supported by the observation that a number of priority genes interact with drugs whose actions are associated with a Parkinsonian clinical phenotype. 45 10 46 Collection of links to Electronic Supplemental Material (ESM) SI_Table_1a http://www.morphonom.net/ng/ESM/t/SI_Table_1a.xls SI_Table_1b http://www.morphonom.net/ng/ESM/t/SI_Table_1b.txt SI_Table_1c http://www.morphonom.net/ng/ESM/t/SI_Table_1c.xls SI_Table_1d http://idconverter.bioinfo.cnio.es/ http://www.morphonom.net/ng/ESM/t/SI_Table_1d.xls SI_Table_1e http://www.affymetrix.com/analysis/index.affx http://www.morphonom.net/ng/ESM/t/SI_Table_1e.xls SI_Table_1f http://www.pdgene.org/ http://www.morphonom.net/ng/ESM/t/SI_Table_1f.xls SI_Table_1g http://www.morphonom.net/ng/ESM/t/SI_Table_1g.rtf SI_Table_1h http://www.morphonom.net/ng/ESM/t/SI_Table_1h.xls http://www.morphonom.net/ng/ESM/r/SI_References_1.rtf SI_Table_2 http://www.morphonom.net/ng/ESM/t/SI_Table_2.xls SI_Table_3 http://www.morphonom.net/ng/ESM/t/SI_Table_3.xls SI_Figures_1a http://www.morphonom.net/ng/ESM/f/SI_Figure_1a.png 3 http://www.morphonom.net/ng/ESM/f/SI_Figures_1a&c-Color_range.jpg http://www.morphonom.net/ng/ESM/f/SI_Figures_1a&c-Labels_used_for_clustering.xls The four probes at the very bottom of the figure (XIST, X (inactive)-specific transcript) in PD01, 9, 10, 16 and 34 identify the female patients in our refined cohort. They served as an internal control. SI_Figures_1b http://www.morphonom.net/ng/ESM/f/SI_Figure_1b.png SI_Figures_1c http://www.morphonom.net/ng/ESM/f/SI_Figure_1c.png SI_Figure_2 47 http://www.morphonom.net/ng/ESM/f/SI_Figure_2.png http://www.morphonom.net/ng/ESM/r/SI_References_2.rtf SI_Figure_3a 2 http://www.morphonom.net/ng/ESM/f/Cell_Processes.html SI_Figure_3b 2 http://www.morphonom.net/ng/ESM/f/Disease.html SI_Figures_4a-c 3 http://www.morphonom.net/ng/ESM/f/892.html http://www.morphonom.net/ng/ESM/f/892s.html http://www.morphonom.net/ng/ESM/f/892h.html SI_Figure_5 http://www.morphonom.net/ng/ESM/f/SI_Figure_5.png SI_Figure_6 4 http://www.morphonom.net/ng/ESM/f/Lewy_Body.html SI_Figure_7 5 http://www.morphonom.net/ng/ESM/f/PD_genes_interactions_with_892_direct_no_DorCP.html SI_Figures_8a-c http://www.morphonom.net/ng/ESM/f/SI_Figure_8a.png http://www.morphonom.net/ng/ESM/f/SI_Figure_8b.png http://www.morphonom.net/ng/ESM/f/SI_Figure_8c.png SI_Pathway_1 http://www.morphonom.net/ng/ESM/p/RET_HSF1_signaling_pathway.html SI_Pathway_2 http://www.morphonom.net/ng/ESM/p/paclitaxel_interactions.html SI_Pathway_3 p http://www.morphonom.net/ng/ESM/p/vincristine_interactions.html SI_References_1 http://www.morphonom.net/ng/ESM/r/SI_References_1.rtf SI_References_2 http://www.morphonom.net/ng/ESM/r/SI_References_2.rtf