5 Machine learning approach identifies new pathways associated with demyelination in a
10.2 Ergänzende Materialien zu Kapitel 5 (Supplemental material to chapter 5)
Supplemental table 5-1: Official gene symbols, q-values, and relative fold changes for all 1210 probe sets differentially expressed between TMEV-infected and mock-infected mice in the time course of TME at a false discovery rate of 1.0%.
Probe set ID Gene symbol Time
Probe set ID Gene symbol Time 1438005_at B230315F11RIK 6 0.0053 1.10 0.4607 -1.13 0.0994 -1.22 0.0104 -1.07 0.1669 1430005_a_at BATF2 5 0.0019 1.15 0.4674 1.61 0.0019 2.38 0.0004 1.56 0.0028
1426083_a_at BTG1 5 0.0010 1.08 0.6124 1.47 0.0007 1.66 0.0027 1.55 0.0000
1437455_a_at BTG1 - 0.0064 1.03 0.7449 1.38 0.0328 1.80 0.0010 1.40 0.0034
Probe set ID Gene symbol Time
1427844_a_at CEBPB - 0.0002 -1.04 0.6839 1.45 0.0042 1.97 0.0027 1.91 0.0002
1418901_at CEBPB 5 0.0001 1.03 0.7688 1.64 0.0002 2.29 0.0003 1.91 0.0000
Probe set ID Gene symbol Time
1436039_at CMAH - 0.0001 -1.00 0.7889 1.23 0.0677 1.82 0.0037 1.87 0.0001
1421214_at CMAH 5 0.0049 -1.06 0.5169 1.33 0.0073 1.34 0.0148 1.46 0.0047
1416776_at CRYM 4 0.0025 1.07 0.6859 1.64 0.0007 2.60 0.0037 2.21 0.0007
1460220_a_at CSF1 5 0.0058 1.11 0.3763 1.39 0.0001 1.57 0.0053 1.40 0.0008
1418652_at CXCL9 2 0.0089 6.01 0.0002 17.31 0.0000 26.82 0.0000 14.29 0.0000
1448710_at CXCR4 3 0.0000 1.14 0.5301 2.55 0.0000 3.86 0.0000 5.52 0.0000
1422978_at CYBB - 0.0001 1.17 0.4273 3.47 0.0000 3.82 0.0000 3.40 0.0000
1436778_at CYBB - 0.0000 2.86 0.0015 12.67 0.0000 21.14 0.0000 15.51 0.0000
Probe set ID Gene symbol Time 1430251_at D330022H12RIK 6 0.0003 1.23 0.1328 1.07 0.4791 -1.19 0.0249 -1.12 0.0623 1455757_at D3ERTD254E 6 0.0013 1.05 0.6518 1.00 0.6176 -1.22 0.0016 -1.12 0.0156 1415827_a_at D3UCLA1 5 0.0000 1.01 0.8052 1.25 0.0109 1.47 0.0015 1.53 0.0001 1415828_a_at D3UCLA1 - 0.0001 -1.05 0.6428 1.55 0.0007 1.91 0.0015 1.92 0.0000
1439189_at D630023B12RIK 5 0.0003 1.02 0.7861 1.24 0.0778 1.69 0.0018 1.83 0.0007
1456481_at D9ERTD280E 6 0.0040 1.07 0.6308 -1.03 0.4963 -1.25 0.0187 -1.27 0.0055 1420498_a_at DAB2 5 0.0080 1.02 0.7969 1.24 0.0561 1.48 0.0190 1.59 0.0022 1422432_at DBI 6 0.0030 -1.05 0.5390 1.04 0.3196 1.08 0.2499 1.20 0.0202 1438093_x_at DBI - 0.0095 -1.06 0.3991 1.04 0.4373 1.13 0.1323 1.11 0.0614
1436562_at DDX58 4 0.0016 1.69 0.0029 2.77 0.0000 3.39 0.0000 2.19 0.0001
1456890_at DDX58 - 0.0062 1.63 0.0210 3.17 0.0000 3.53 0.0000 2.24 0.0001
1455436_at DIRAS2 6 0.0040 1.04 0.7037 -1.04 0.2799 -1.13 0.0168 -1.14 0.0041
1437927_at DLGH2 6 0.0091 1.07 0.6582 -1.00 0.6014 -1.14 0.0188 -1.21 0.0034
1452792_at DZIP1 6 0.0086 1.09 0.5176 -1.07 0.1215 -1.11 0.0623 -1.18 0.0064
1438135_at E130114P18RIK 6 0.0079 -1.09 0.5131 -1.30 0.0680 -1.28 0.0115 1.18 0.2236 1422120_at EAF2 5 0.0016 -1.12 0.4828 1.24 0.1617 1.43 0.0103 1.56 0.0015 1437356_at EBI2 5 0.0070 -1.13 0.3955 1.22 0.1071 1.63 0.0309 1.91 0.0113
1451218_at EDEM1 - 0.0038 1.13 0.3340 1.55 0.0000 1.73 0.0041 1.71 0.0001
1424065_at EDEM1 3 0.0000 1.18 0.3963 4.39 0.0000 6.02 0.0000 5.41 0.0000
Probe set ID Gene symbol Time
1434814_x_at GPI1 6 0.0022 1.03 0.4212 -1.01 0.4791 -1.04 0.0526 -1.07 0.0113
1448303_at GPNMB 2 0.0000 -1.05 0.5991 6.94 0.0000 29.60 0.0000 33.51 0.0000
Probe set ID Gene symbol Time
1451567_a_at IFI203 3 0.0032 2.09 0.0038 4.33 0.0000 6.21 0.0000 4.54 0.0000
1452348_s_at IFI205 3 0.0000 1.19 0.2239 3.30 0.0003 8.61 0.0000 3.05 0.0008
1422476_at IFI30 3 0.0000 1.37 0.1109 3.14 0.0000 4.61 0.0000 3.02 0.0000
Probe set ID Gene symbol Time
1425738_at IGK 2 0.0000 1.13 0.5680 11.70 0.0016 34.80 0.0000 61.61 0.0000
1427792_at IGK-V28 - 0.0008 1.04 0.7514 38.44 0.0000 42.71 0.0000 9.86 0.0044
1452463_x_at IGK-V8 1 0.0000 3.55 0.0012 235.93 0.0000 302.47 0.0000 234.09 0.0000
Probe set ID Gene symbol Time
1460245_at KLRD1 3 0.0034 1.53 0.0296 2.80 0.0023 5.53 0.0001 3.10 0.0000
1450495_a_at KLRK1 4 0.0049 1.24 0.2511 2.89 0.0001 2.87 0.0001 1.83 0.0001
1434227_at KRTDAP 6 0.0005 1.02 0.7544 -1.15 0.1691 -1.05 0.3504 1.60 0.0028
1430570_at KYNU 5 0.0001 -1.10 0.4645 1.22 0.0361 1.78 0.0016 1.66 0.0017
Probe set ID Gene symbol Time
1449874_at LY96 4 0.0001 1.08 0.6434 1.74 0.0011 2.85 0.0001 2.53 0.0000
1451318_a_at LYN 4 0.0001 1.44 0.0089 2.37 0.0000 2.64 0.0000 2.31 0.0000
Probe set ID Gene symbol Time
1419599_s_at MS4A6D 2 0.0001 2.62 0.0004 8.86 0.0000 11.79 0.0000 9.38 0.0000
1419598_at MS4A6D 3 0.0001 2.08 0.0024 6.77 0.0000 9.86 0.0000 6.98 0.0000
Probe set ID Gene symbol Time
Probe set ID Gene symbol Time
1424556_at PYCR1 5 0.0036 -1.10 0.5669 1.15 0.3621 1.70 0.0162 1.83 0.0036
1417741_at PYGL 5 0.0001 -1.16 0.3865 1.11 0.2637 1.48 0.0100 1.53 0.0004
1455819_at ROD1 5 0.0034 1.16 0.3690 1.46 0.0009 1.76 0.0008 1.61 0.0000
1456590_x_at RP23-382C18.5 6 0.0027 -1.28 0.3028 -1.07 0.3763 1.31 0.0233 1.13 0.0814 1418896_a_at RPN2 6 0.0010 -1.07 0.1632 1.04 0.5268 1.16 0.0753 1.11 0.0599
1421457_a_at SAMSN1 5 0.0064 1.02 0.7581 1.40 0.0214 1.97 0.0000 1.46 0.0407
1420502_at SAT1 5 0.0027 1.03 0.7809 1.33 0.0122 1.52 0.0062 1.51 0.0001
Probe set ID Gene symbol Time
1417695_a_at SOAT1 4 0.0000 1.12 0.5709 1.68 0.0002 2.75 0.0000 2.53 0.0000
1417696_at SOAT1 - 0.0001 1.00 0.7777 1.40 0.0114 2.08 0.0002 1.98 0.0001
Probe set ID Gene symbol Time
1448623_at TMEM123 5 0.0023 -1.06 0.5838 1.26 0.0754 1.45 0.0152 1.47 0.0016
1417222_a_at TMEM123 - 0.0069 -1.09 0.6150 1.20 0.1365 1.67 0.0103 1.37 0.0113
Probe set ID Gene symbol Time
Probe set ID Gene symbol Time
1442118_at - 0.0000 1.03 0.7756 1.59 0.0026 2.71 0.0000 3.26 0.0000
1448021_at - 0.0000 1.26 0.3154 4.29 0.0000 7.21 0.0000 5.56 0.0000
1436530_at - 0.0001 1.15 0.5069 2.99 0.0000 5.31 0.0000 4.17 0.0001
1439799_at - 0.0001 1.11 0.4056 -1.08 0.1340 -1.34 0.0088 -1.21 0.0056
1439831_at - 0.0001 4.11 0.0011 20.91 0.0000 34.01 0.0000 25.12 0.0000
1448775_at - 0.0001 1.70 0.0047 1.83 0.0000 4.91 0.0000 3.26 0.0000
1438027_at - 0.0014 2.98 0.0003 6.94 0.0000 9.63 0.0000 7.43 0.0000
1435629_at - 0.0015 1.20 0.3009 -1.08 0.2858 -1.33 0.0397 -1.31 0.0130
1443170_at - 0.0015 1.10 0.5592 -1.01 0.5623 -1.16 0.0085 -1.15 0.0018
1457287_at - 0.0020 -1.00 0.7980 1.19 0.1945 1.44 0.0154 1.58 0.0012
1452408_at - 0.0023 1.19 0.4339 2.04 0.0029 3.11 0.0001 3.12 0.0002
1456523_at - 0.0029 -1.06 0.2902 1.03 0.6039 -1.31 0.0055 -1.34 0.0012
1438855_x_at - 0.0032 1.31 0.1498 3.11 0.0000 4.02 0.0014 4.04 0.0000
1443157_at - 0.0043 1.24 0.1605 1.07 0.4811 -1.11 0.0526 -1.14 0.0952
1442201_at - 0.0061 1.23 0.3263 1.84 0.0002 2.19 0.0000 2.03 0.0001
1455180_at - 0.0064 -1.08 0.5409 1.23 0.2116 1.38 0.0641 1.76 0.0012
1444744_at - 0.0096 1.15 0.3615 -1.08 0.2759 -1.27 0.0269 1.04 0.5326
1428544_at 0610007L01RIK 5 0.0094 -1.09 0.4728 1.18 0.0442 1.26 0.0576 1.13 0.0429 1423909_at 0610011I04RIK 5 0.0001 1.03 0.7693 1.42 0.0003 1.65 0.0039 1.93 0.0000 1441811_x_at 0610011I04RIK - 0.0034 1.02 0.7832 1.29 0.0289 1.56 0.0124 1.72 0.0008 1425780_a_at 0610041E09RIK 6 0.0088 -1.12 0.2768 1.02 0.6184 1.07 0.1019 1.08 0.1458 1424354_at 1110007F12RIK 3 0.0000 1.58 0.0429 4.61 0.0000 6.95 0.0000 6.84 0.0000 1438176_x_at 1110031B06RIK 6 0.0038 -1.01 0.7464 -1.02 0.3181 -1.11 0.0056 -1.10 0.0025 1437981_x_at 1110057K04RIK 5 0.0001 1.05 0.6909 1.34 0.0113 2.02 0.0026 2.33 0.0001 1424524_at 1200002N14RIK 4 0.0001 1.21 0.3502 1.65 0.0002 3.35 0.0002 2.90 0.0000 1427007_at 1200013B08RIK 4 0.0024 1.34 0.0355 2.22 0.0000 2.75 0.0000 2.11 0.0003 1453234_at 1300002K09RIK 5 0.0014 -1.08 0.5318 1.15 0.3614 1.86 0.0161 2.25 0.0019 1438641_x_at 1500016O10RIK 6 0.0081 -1.04 0.5950 -1.02 0.4752 -1.16 0.0195 -1.28 0.0028 1424444_a_at 1600014C10RIK 5 0.0001 1.01 0.8074 1.32 0.0057 1.65 0.0037 1.32 0.0030 1424022_at 1700012B18RIK 5 0.0049 -1.06 0.6778 1.13 0.3751 1.62 0.0025 1.65 0.0028 1458178_at 1700012H17RIK 6 0.0020 1.10 0.5519 -1.02 0.5237 -1.25 0.0154 -1.36 0.0014 1418004_a_at 1810009M01RIK 5 0.0016 1.07 0.6417 1.32 0.0003 1.51 0.0075 1.62 0.0002 1449842_at 1810059G22RIK 5 0.0032 1.03 0.7932 1.25 0.0359 1.48 0.0091 1.42 0.0007 1451965_at 19-25 2 0.0001 1.07 0.6673 9.40 0.0059 20.44 0.0012 20.03 0.0000 1428947_at 2010001M09RIK 2 0.0000 1.29 0.1890 9.09 0.0000 12.92 0.0000 13.41 0.0000 1425193_at 2010106G01RIK 5 0.0021 -1.11 0.4349 1.18 0.0720 1.34 0.0210 1.19 0.0349 1433645_at 2210409B22RIK 5 0.0001 -1.05 0.5653 1.06 0.3565 1.38 0.0123 1.50 0.0016 1431299_a_at 2310014H01RIK 5 0.0004 1.09 0.5009 1.57 0.0001 1.79 0.0005 1.66 0.0001 1455126_x_at 2310028O11RIK 6 0.0054 -1.04 0.3508 -1.07 0.0456 -1.10 0.0146 -1.15 0.0001 1452227_at 2310045A20RIK 5 0.0063 1.00 0.8074 1.18 0.0998 1.24 0.0591 1.49 0.0034 1452834_at 2600010E01RIK 6 0.0001 1.05 0.6904 -1.06 0.0967 -1.30 0.0140 -1.38 0.0029 1455135_at 2610014I16RIK 6 0.0024 -1.00 0.8055 -1.08 0.0600 -1.22 0.0059 -1.15 0.0038 1453769_at 2610318C08RIK 5 0.0088 -1.24 0.1164 1.31 0.0035 1.21 0.1025 1.05 0.4698 1434742_s_at 2810401C16RIK 6 0.0019 1.10 0.4610 -1.07 0.1711 -1.27 0.0443 -1.20 0.0012 1419153_at 2810417H13RIK 4 0.0001 1.16 0.4365 2.17 0.0001 3.02 0.0000 1.78 0.0007 1459684_at 2810449C10RIK 6 0.0028 -1.21 0.0744 -1.06 0.3267 1.03 0.5621 1.11 0.1426 1424624_at 2900011O08RIK 6 0.0076 -1.01 0.7449 -1.10 0.0036 -1.13 0.0210 -1.17 0.0002 1443707_at 2900046B09RIK 6 0.0085 1.05 0.6333 -1.04 0.3561 -1.19 0.0177 -1.11 0.0315 1419118_at 2900093B09RIK 6 0.0080 1.02 0.7960 -1.10 0.0413 -1.26 0.0235 -1.25 0.0048
Probe set ID Gene symbol Time 1426964_at 3110003A17RIK 5 0.0028 1.03 0.7785 1.23 0.0194 1.37 0.0082 1.26 0.0012 1433875_at 4732418C07RIK 6 0.0001 1.06 0.6259 -1.00 0.6172 -1.17 0.0121 -1.19 0.0010 1439712_at 4921521J11RIK 6 0.0094 1.50 0.0098 1.07 0.5137 -1.06 0.3610 -1.05 0.3340 1429682_at 4930431B09RIK 3 0.0000 -1.10 0.5570 3.45 0.0000 5.46 0.0000 4.98 0.0000 1432030_at 4930434J06RIK 6 0.0053 -1.31 0.0152 -1.05 0.4135 1.05 0.5136 -1.01 0.4961 1415717_at 4931406I20RIK 6 0.0001 1.10 0.2314 -1.01 0.4998 -1.12 0.0247 -1.15 0.0072 1447711_x_at 4933412E12RIK 5 0.0001 1.08 0.6245 1.29 0.0496 2.12 0.0001 1.48 0.0003 1430064_at 4933424A20RIK 6 0.0048 -1.04 0.6292 -1.12 0.1298 -1.23 0.0105 -1.38 0.0010 1454606_at 4933426M11RIK 5 0.0001 -1.04 0.6518 1.20 0.0698 1.44 0.0093 1.43 0.0003 1460361_at 5033414D02RIK 5 0.0001 1.11 0.3615 1.27 0.0113 1.56 0.0000 1.42 0.0005 1430373_at 5430427O19RIK 5 0.0009 1.10 0.5807 1.52 0.0031 2.10 0.0016 2.21 0.0001 1429171_a_at 5730507H05RIK 5 0.0031 -1.07 0.6133 1.35 0.0233 1.60 0.0065 1.37 0.0045 1426362_at 5730537D05RIK 6 0.0061 1.05 0.6888 -1.11 0.1776 -1.23 0.0081 -1.23 0.0072 1452203_at 5830411E10RIK 6 0.0025 -1.20 0.1573 1.07 0.4636 1.19 0.0693 1.07 0.1774 1418776_at 5830443L24RIK 1 0.0002 4.07 0.0018 33.74 0.0000 55.12 0.0000 43.59 0.0000 1438024_at 6230416A05RIK 5 0.0080 1.01 0.8036 1.15 0.0255 1.32 0.0174 1.27 0.0112 1426766_at 6330403K07RIK 6 0.0019 -1.02 0.5052 -1.04 0.2910 -1.21 0.0031 -1.12 0.0028 1455218_at 6330503K22RIK 6 0.0009 1.06 0.6093 -1.16 0.0384 -1.39 0.0162 -1.19 0.0052 1455885_at 6530401C20RIK 5 0.0047 -1.00 0.7929 1.21 0.0843 1.59 0.0089 1.45 0.0068 1430448_at 6720418B01RIK 6 0.0009 1.35 0.0627 1.17 0.1827 -1.22 0.0290 -1.05 0.3511 1423072_at 6720475J19RIK 6 0.0084 1.27 0.1447 -1.01 0.5517 -1.44 0.0051 1.03 0.5065 1453352_at 9030605H24RIK 6 0.0004 1.05 0.7228 -1.17 0.0226 -1.31 0.0080 -1.42 0.0013 1439143_at 9330167E06 6 0.0056 1.29 0.1257 -1.12 0.1657 -1.25 0.0697 -1.25 0.0622 1455581_x_at 9530028C05 5 0.0082 1.33 0.0902 1.59 0.0054 2.56 0.0003 1.58 0.0002 1436183_at 9830115L13RIK 3 0.0075 2.13 0.0002 3.61 0.0000 3.69 0.0000 2.99 0.0000 1425156_at 9830147J24RIK 2 0.0001 2.68 0.0006 8.72 0.0000 11.61 0.0000 5.49 0.0000 1434380_at 9830147J24RIK - 0.0005 2.98 0.0014 9.29 0.0000 11.28 0.0000 7.21 0.0000 1437245_at 9930117H01RIK 5 0.0002 1.11 0.5163 1.26 0.1822 1.78 0.0154 2.31 0.0000 1436974_at A230069A22RIK 6 0.0051 1.03 0.7650 -1.10 0.0292 -1.22 0.0104 -1.21 0.0010 1455358_at A2BP1 6 0.0100 1.06 0.6483 -1.06 0.3261 -1.17 0.0130 -1.17 0.0056 1455132_at A430107D22RIK 4 0.0058 1.82 0.0015 2.47 0.0000 3.33 0.0000 3.36 0.0000 1442023_at A530030E21RIK 5 0.0000 -1.13 0.4079 1.48 0.0022 1.65 0.0001 2.96 0.0000 1436576_at A630077B13RIK 3 0.0000 1.55 0.0902 7.37 0.0000 11.15 0.0000 6.18 0.0000 1458484_at A730020M07RIK 6 0.0067 -1.04 0.6830 -1.15 0.2170 -1.51 0.0048 -1.57 0.0035 1434046_at AA467197 4 0.0004 1.15 0.3777 2.17 0.0001 3.06 0.0004 2.28 0.0000 1438475_at AB124611 3 0.0001 1.70 0.0288 4.62 0.0000 9.23 0.0000 4.51 0.0000
Probe set ID = The probe set ID represents the unique probe set identifier of the Affymetrix mouse genome 430 2.0 array.
K-means cluster = The number refers to the respective cluster of genes with a similar expression pattern in k-means cluster analysis as displayed in Fig.5-3 and Table 5-I.
q-value = Significant differential gene expression between TMEV-infected and mock-infected mice in the time course of TME was determined employing the spline-based method embedded in EDGE. Additionally, q-values were calculated independently for each time point (14, 42, 98, 196 dpi). A time course q-value of ≤ 0.01 was selected to designate significant changes in gene expression, and simultaneously limit the maximally allowed false discovery rate to 1%.
Fold change = The fold change was calculated as the ratio of the inverse-transformed arithmetic means of the log2-transformed expression values of TMEV-infected versus mock-infected mice. Down-regulations are shown as negative reciprocal values.
Supplemental table 5-2: Results of the functional annotation clustering of all 1001 differentially expressed genes. The table shows the functional annotation clusters containing more than 50% significantly enriched gene ontology terms at a false discovery rate of 1.0%.
Functional
immune response 122 0.0000
response to stimulus 212 0.0000
2 antigen processing and presentation 32 0.0000
antigen processing and presentation of peptide antigen 22 0.0000 antigen processing and presentation of exogenous antigen 17 0.0000 antigen processing and presentation of exogenous peptide antigen 15 0.0000 antigen processing and presentation of exogenous peptide antigen via
MHC class II 13 0.0000
antigen processing and presentation of peptide antigen via MHC class II
13 0.0000 antigen processing and presentation of peptide or polysaccharide
antigen via MHC class II 13 0.0000
3 defense response 89 0.0000
inflammatory response 44 0.0000
response to wounding 53 0.0000
response to external stimulus 69 0.0000
response to stress 77 0.3000
4 regulation of immune response 38 0.0000
regulation of immune system process 38 0.0000
leukocyte mediated immunity 33 0.0000
positive regulation of immune response 32 0.0000
immune effector process 38 0.0000
positive regulation of immune system process 32 0.0000
lymphocyte mediated immunity 31 0.0000
adaptive immune response based on somatic recombination of
immune receptors built from immunoglobulin superfamily domains 31 0.0000
adaptive immune response 31 0.0000
activation of immune response 27 0.0000
B cell mediated immunity 26 0.0000
regulation of multicellular organismal process 55 0.0000
immunoglobulin mediated immune response 25 0.0000
positive regulation of multicellular organismal process 32 0.0000
inflammatory response 44 0.0000
immune response-regulating signal transduction 15 0.0000
humoral immune response 18 0.0000
acute inflammatory response 21 0.0000
immune response-activating signal transduction 14 0.0000 immune response-regulating cell surface receptor signaling pathway 13 0.0000 activation of plasma proteins during acute inflammatory response 13 0.0000
complement activation 13 0.0000
immune response-activating cell surface receptor signaling pathway 12 0.0000 humoral immune response mediated by circulating immunoglobulin 11 0.0000
complement activation, classical pathway 10 0.1000
B cell receptor signaling pathway 5 1.5000
antigen receptor-mediated signaling pathway 8 2.7000
5 cell activation 60 0.0000
leukocyte activation 57 0.0000
lymphocyte activation 49 0.0000
regulation of multicellular organismal process 55 0.0000
Functional
regulation of lymphocyte activation 25 0.0000
regulation of cell activation 25 0.0000
immune system development 44 0.0000
hemopoietic or lymphoid organ development 41 0.0000
T cell differentiation 19 0.0000
leukocyte differentiation 28 0.0000
lymphocyte differentiation 23 0.0000
hemopoiesis 37 0.0000
positive regulation of lymphocyte activation 17 0.0000
regulation of lymphocyte proliferation 12 2.8000
regulation of mononuclear cell proliferation 12 2.8000
myeloid cell differentiation 14 30.9000
6 signal transduction 218 0.0000
cell communication 234 0.0000
cell surface receptor linked signal transduction 119 0.0000
intracellular signaling cascade 101 0.9000
7 response to other organism 27 0.0000
multi-organism process 32 0.0000
response to biotic stimulus 33 0.0000
response to virus 13 0.1000
response to bacterium 14 4.5000
8 regulation of inflammatory response to antigenic stimulus 9 0.0000
inflammatory response to antigenic stimulus 9 0.0000
regulation of lymphocyte mediated immunity 9 0.0000
regulation of leukocyte mediated immunity 9 0.0000
regulation of acute inflammatory response 8 0.0000
regulation of hypersensitivity 8 0.0000
regulation of acute inflammatory response to antigenic stimulus 8 0.0000
regulation of adaptive immune response 10 0.0000
regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains.
10 0.0000
regulation of immune effector process 9 0.0000
regulation of B cell mediated immunity 7 0.0000
regulation of immunoglobulin mediated immune response 7 0.0000
hypersensitivity 8 0.0000
myeloid leukocyte mediated immunity 8 0.0000
acute inflammatory response to antigenic stimulus 8 0.0000
phagocytosis, engulfment 8 0.0000
regulation of phagocytosis 9 0.0000
positive regulation of phagocytosis 9 0.0000
phagocytosis 12 0.0000
positive regulation of inflammatory response to antigenic stimulus 7 0.0000
regulation of inflammatory response 11 0.0000
regulation of defense response 11 0.0000
positive regulation of inflammatory response 8 0.0000 positive regulation of adaptive immune response 8 0.0000 positive regulation of adaptive immune response based on somatic
recombination of immune receptors built from immunoglobulin superfamily domains
8 0.0000
positive regulation of defense response 8 0.0000
type II hypersensitivity 6 0.0000
type IIa hypersensitivity 6 0.0000
positive regulation of type IIa hypersensitivity 6 0.0000
regulation of type IIa hypersensitivity 6 0.0000
Functional 8 (continued) regulation of type II hypersensitivity 6 0.0000
positive regulation of type II hypersensitivity 6 0.0000 positive regulation of myeloid leukocyte mediated immunity 6 0.0000 regulation of myeloid leukocyte mediated immunity 6 0.0000 positive regulation of leukocyte mediated immunity 7 0.1000 positive regulation of lymphocyte mediated immunity 7 0.1000 positive regulation of acute inflammatory response 6 0.1000 positive regulation of B cell mediated immunity 6 0.1000 positive regulation of immunoglobulin mediated immune response 6 0.1000 positive regulation of acute inflammatory response to antigenic
stimulus 6 0.1000
positive regulation of hypersensitivity 6 0.1000
positive regulation of immune effector process 7 0.1000
positive regulation of endocytosis 9 0.2000
phagocytosis, recognition 6 0.3000
regulation of type I hypersensitivity 5 0.8000
regulation of response to stimulus 11 0.8000
positive regulation of transport 10 1.5000
type I hypersensitivity 5 2.5000
regulation of endocytosis 9 3.8000
antibody-dependent cellular cytotoxicity 4 3.8000
leukocyte mediated cytotoxicity 7 4.8000
cell killing 7 5.9000
positive regulation of type I hypersensitivity 4 7.1000
cell recognition 9 13.7000
membrane organization and biogenesis 27 16.6000
regulation of type III hypersensitivity 3 18.4000
positive regulation of type III hypersensitivity 3 18.4000
type III hypersensitivity 3 18.4000
antigen processing and presentation of exogenous peptide antigen via MHC class I
3 18.4000
endocytosis 18 57.8000
membrane invagination 18 57.8000
regulation of transport 10 98.8000
vesicle-mediated transport 25 100.0000
9 chemotaxis 23 0.0000
taxis 23 0.0000
locomotory behavior 27 0.7000
response to chemical stimulus 42 1.7000
behavior 33 7.7000
10 T cell differentiation 19 0.0000
lymphocyte differentiation 23 0.0000
positive regulation of lymphocyte activation 17 0.0000
regulation of T cell activation 17 0.0000
positive regulation of T cell activation 12 0.5000
regulation of lymphocyte differentiation 8 1.7000
regulation of T cell differentiation 7 1.7000
positive regulation of lymphocyte differentiation 6 5.1000 positive regulation of T cell differentiation 5 11.2000
11 induction of programmed cell death 33 0.0000
induction of apoptosis 33 0.0000
positive regulation of apoptosis 36 0.0000
positive regulation of programmed cell death 36 0.0000
regulation of apoptosis 58 0.0000
regulation of programmed cell death 58 0.0000
cell death 79 0.0000
Functional
programmed cell death 75 0.0000
apoptosis 74 0.0000
positive regulation of cellular process 89 0.0000
cell development 96 15.0000
cell differentiation 135 20.2000
cellular developmental process 135 20.2000
developmental process 195 90.9000
multicellular organismal process 187 98.2000
organ development 88 100.0000
system development 107 100.0000
anatomical structure development 122 100.0000
multicellular organismal development 131 100.0000
12 antigen processing and presentation of peptide antigen via MHC class I
10 0.0000 antigen processing and presentation of endogenous peptide antigen 5 0.8000 antigen processing and presentation of endogenous peptide antigen
via MHC class I
5 0.8000 antigen processing and presentation of endogenous antigen 5 2.5000
13 cytokine production 28 0.0000
regulation of cytokine biosynthetic process 19 0.0000
cytokine metabolic process 20 0.0000
cytokine biosynthetic process 20 0.0000
positive regulation of cytokine biosynthetic process 14 0.0000
tumor necrosis factor biosynthetic process 7 0.0000
regulation of tumor necrosis factor biosynthetic process 7 0.0000
positive regulation of translation 14 0.0000
regulation of translation 25 0.0000
positive regulation of cellular biosynthetic process 14 0.1000
regulation of biosynthetic process 27 0.1000
regulation of cellular biosynthetic process 25 0.1000 positive regulation of biosynthetic process 15 0.1000 positive regulation of protein metabolic process 15 3.5000
regulation of protein metabolic process 31 3.6000
translation 31 100.0000
biosynthetic process 80 100.0000
cellular biosynthetic process 59 100.0000
positive regulation of cellular metabolic process 28 100.0000
macromolecule biosynthetic process 43 100.0000
positive regulation of metabolic process 29 100.0000
14 regulation of lymphocyte activation 25 0.0000
regulation of cell activation 25 0.0000
positive regulation of lymphocyte activation 17 0.0000
lymphocyte proliferation 18 0.0000
mononuclear cell proliferation 18 0.0000
regulation of T cell activation 17 0.0000
positive regulation of T cell activation 12 0.5000
regulation of lymphocyte proliferation 12 2.8000
regulation of mononuclear cell proliferation 12 2.8000
T cell proliferation 11 9.9000
positive regulation of mononuclear cell proliferation 7 61.1000 positive regulation of lymphocyte proliferation 7 61.1000 positive regulation of T cell proliferation 6 64.2000
regulation of T cell proliferation 7 82.3000
15 positive regulation of cytokine biosynthetic process 14 0.0000
tumor necrosis factor biosynthetic process 7 0.0000
Functional annotation cluster
Gene ontology terms Number
of genes FDR (%) 15 (continued) regulation of tumor necrosis factor biosynthetic process 7 0.0000
tumor necrosis factor production 8 0.0000
positive regulation of translation 14 0.0000
positive regulation of cellular biosynthetic process 14 0.1000 positive regulation of tumor necrosis factor biosynthetic process 6 0.1000 positive regulation of biosynthetic process 15 0.1000 innate immune response-activating signal transduction 5 0.8000
activation of innate immune response 5 0.8000
regulation of innate immune response 6 0.9000
positive regulation of cytokine production 7 1.3000
positive regulation of protein metabolic process 15 3.5000 positive regulation of tumor necrosis factor production 4 3.8000 pattern recognition receptor signaling pathway 4 3.8000 positive regulation of innate immune response 5 5.8000
regulation of cytokine production 7 10.6000
regulation of tumor necrosis factor production 4 11.7000
response to molecule of fungal origin 3 18.4000
toll-like receptor signaling pathway 3 32.4000
innate immune response activating cell surface receptor signaling pathway
3 32.4000
response to fungus 4 46.7000
Functional annotation cluster = Groups of functionally related gene ontology terms derived by DAVIDs functional annotation clustering tool with medium stringency settings. Only those functional annotation clusters containing ≥ 50% significantly enriched gene ontology terms at a false discovery rate of 1.0% were selected.
Gene ontology terms = Terms of the category “biological process” from the gene ontology database.
Number of genes = Number of genes out of the 1001 differentially expressed genes between the TMEV-infected and mock-infected mice associated with the respective gene ontology term.
FDR = False discovery rate of significant enrichment for the respective gene ontology term.
Supplemental table 5-3: Top 100 pathways associated with demyelination derived by LeFE.
(%) Top 5 genes and gene importance values 1 sterol metabolism 16 0.0010 12.5 (Dhcr7, 3 lipid biosynthesis 46 0.0020 16.7 (Fdft1,
5.534)
synaptic plasticity 3 0.0030 18.8 (Apoe, 8.868) (S100b,
transferase activity 66 0.0050 18.8 (Tlr4, 6.244) (Plce1, 8 protein prenylation 4 0.0060 18.8 (Fntb,
8.933) (Fnta,
morphogenesis 29 0.0085 19.6 (Apoe, 4.994) (S100b, 22 steroid metabolism 45 0.0105 19.6 (Fdft1,
5.535) (Dhcr7,
Rank Categories Category size Median
category p-value
FDR
(%) Top 5 genes and gene importance values 24 signal complex
formation 6 0.0110 19.6 (Mapk8i
p2, 6.09) (Ptk2b, 39 synaptogenesis 14 0.0150 19.6 (Apoe,
6.017) (S100b,
Rank Categories Category size Median
category p-value
FDR
(%) Top 5 genes and gene importance values 47 isoprenoid
protein metabolism 65 0.0240 19.6 (Tlr4, 6.358) (Eif4g1,
Rank Categories Category size Median
category p-value
FDR
(%) Top 5 genes and gene importance values 72 interleukin-13 78 protein-lipoylation 3 0.0325 19.6 (Nnat,
7.845) (Nmt1,
catabolism 10 0.0360 19.6 (Cyp46a 1, 5.238) (Prdx6,
transduction 92 0.0435 19.6 (Plce1, 4.701) (Rgs5,
Rank Categories Category size Median
category p-value
FDR
(%) Top 5 genes and gene importance values
96 exocytosis 13 0.0435 19.6 (Cplx2,
Categories = Terms of the category “biological process” from the gene ontology database.
Category size = Number of genes out of the 19238 unique official gene symbols of the Affymetrix mouse genome 430 2.0 array associated with the respective category.
Median category p-value = The median p-value of the respective category is used for ranking the categories and should not be used as a metric of statistical significance. According to Eichler et al. (2007), p-values < 0.04 represent possible biological associations between the category and the biology represented by the signature file.
FDR = False discovery rate of the respective category for the probability of observing any other category with an association to demyelination that is more significant by chance.
Top 5 genes and gene importance values = A variable length list containing the genes and their corresponding median importance scores. According to Eichler et al. (2007), genes with importance scores that are greater than 0.8 have represent possible biological importance, although that can vary between different data sets.