Lejeune et al. BMC Genomics 2012, 13:91 http://www.biomedcentral.com/1471-2164/13/91 Page 9 of 14 Table 2 Pathway analysis for 399 genes that reduced 128Q-neuron dysfunction when knocked-down by RNAi (Continued) Angiogenesis 0.00520 C06B3.4/stdh-1, F11A5.12/stdh-2, K04A8.5 mRNA splicing 0.00534 F56A8.7/unc-64, K02D10.5, Y22F5A.3/ric-4, Y48B6A.8/ace-3 Muscarinic acetylcholine receptor 1 0.00608 F56A8.7/unc-64, K02D10.5, Y22F5A.3/ric-4, Y48B6A.8/ace-3 and 3 signaling Alanine biosynthesis 0.00769 K02D10.5, K08F8.4/pah-1, Y22F5A.3/ric-4 Butanoate metabolism 0.00777 C06B3.4/stdh-1, F11A5.12/stdh-2, K03A1.5/sur-5, T02G5.7 5-Hydroxytryptamine biosynthesis 0.00798 K02D10.5, Y22F5A.3/ric-4 Interleukin signaling 0.00974 C47G2.2/unc-130, F38A6.1/pha-4, F43C1.2/mpk-1, Y18D10A.5/gsk-3 Amino sugar and nucleotide sugar 0.01084 C01F1.3, C53B4.7/bre-1, K08E3.5, T14F9.3/hex-1 metabolism Metabotropic glutamate receptor 0.01254 F56A8.7/unc-64, K02D10.5, Y22F5A.3/ric-4 group II pathway Linoleic acid metabolism 0.01511 C06B3.4/stdh-1, F11A5.12/stdh-2 Beta3 adrenergic receptor signaling 0.01511 K02D10.5, Y22F5A.3/ric-4 Integrin signaling 0.01742 B0218.3/pmk-1, B0478.1/jnk-1, C27B7.8/rap-1, C36B1.1/cle-1, F43C1.2/mpk-1 p53 pathway by glucose deprivation 0.01908 C47G2.2/unc-130, F38A6.1/pha-4, F48E8.1/lon-1, Y18D10A.5/gsk-3 5-Hydroxytryptamine degredation 0.01939 K02D10.5, Y22F5A.3/ric-4 Ornithine degradation 0.02121 B0218.3/pmk-1, B0478.1/jnk-1, T19B10.11/mxl-1 Cortocotropin releasing factor 0.02412 K02D10.5, Y22F5A.3/ric-4 receptor signaling FGF signaling 0.02627 B0218.3/pmk-1, B0478.1/jnk-1, F26E4.1/sur-6, F43C1.2/mpk-1 N-acetylglucosamine metabolism 0.02712 F56A8.7/unc-64, K02D10.5, T02C12.1/hum-5, Y22F5A.3/ric-4, Y48B6A.8/ace-3 5HT3 type receptor mediated 0.02928 K02D10.5, Y22F5A.3/ric-4 signaling B cell activation 0.02939 B0218.3/pmk-1, B0478.1/jnk-1, F43C1.2/mpk-1 Fructose and mannose metabolism 0.03565 C06B3.4/stdh-1, C53B4.7/bre-1, F11A5.12/stdh-2 Pantothenate and CoA biosynthesis 0.04074 F25H9.6, T04G9.4 Alzheimer disease-amyloid secretase 0.04074 K02D10.5, Y22F5A.3/ric-4 pathway Beta1 adrenergic receptor signaling 0.04074 K02D10.5, Y22F5A.3/ric-4 Beta2 adrenergic receptor signaling 0.04074 K02D10.5, Y22F5A.3/ric-4 EGF receptor signaling 0.04229 B0218.3/pmk-1, B0478.1/jnk-1, C27B7.8/rap-1, F43C1.2/mpk-1 Toll receptor signaling 0.04494 C08B6.9/aos-1, F11A10.1/lex-1, F40G9.3/ubc-20, Y49E10.1/rpt-6 Alanine, aspartate and glutamate 0.04494 C04E7.2/sor-3, C34E10.7/cnd-1, C47G2.2/unc-130, F57H12.7/mec-17 metabolism Serine glycine biosynthesis 0.04620 B0478.1/jnk-1, F43C1.2/mpk-1, Y38F1A.10/max-2 Lysine biosynthesis 0.04869 C25A11.4/ajm-1, C36B1.1/cle-1, F17E5.1/lin-2, F22B5.1/evl-20, F43C9.4/mig-13, F56A8.7/unc-64, Y22F5A.3/ric-4 Pathway analysis was based on hypergeomeric tests using pathways from Wormbook, KEGG and Panther. P < 0.05 was considered significant and results are shown by increasing P values. (S score) was available (genes that either modulate 128Q-neuron dysfunction or produce no effect when knocked-down by RNAi). The modules resulting from this analysis were annotated by using Gene Ontology, KEGG and Panther pathways and gene lists of interest (conserved genes, druggable genes, htt partners, genes involved in autophagy, mitochondrial function and synaptic activity). These analyses identified a more reli- able set of 286 modifier genes as distributed in 137 modules for suppression of 128Q-neuron dysfunction by RNAi and 105 modules for aggravation of 128Q-neuron dysfunction by RNAi (Additional file 9: Table S8; Additional file 10: Table S9). Modules of variable sizes were obtained (2-50 genes) for either suppression or aggravation of 128Q-neuron dysfunction. Of note, small modules are equally significant compared to large mod- ules as the size of the resulting modules was always dri- ven by the stable and best balance between gene connectivity and gene activity during the spectral decomposition process (see Materials and Methods). The modules and their content can be visualized using a freely-accessible database (see http://www.broca.inserm. fr/EHDN2/RNAiscreen) that contains a query page and interactive graphical interface [36]. Our network-based