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<?xml version="1.0" encoding="UTF-8"?><!DOCTYPE collection SYSTEM "BioC.dtd"><collection><source>BioC-API</source><date>20250306</date><key>collection.key</key><document><id>ACEL-19-e13153-s001.docx</id><passage><infon key="license">=</infon><infon key="tar">https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_package/80/25/PMC7294781.tar.gz</infon><infon key="source">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294781/bin/ACEL-19-e13153-s001.docx</infon><infon key="citation">Aging Cell. 2020 Jun 17; 19(6):e13153</infon><infon key="article-id_pmc">PMC7294781</infon><infon key="article-id_pmid">32419307</infon><infon key="section_type">TITLE</infon><infon key="id">Front_1</infon><infon key="type">front</infon><offset>0</offset><text>Supplementary Material</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_1</infon><infon key="type">text</infon><offset>23</offset><text>Supplementary Information</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_2</infon><infon key="type">text</infon><offset>49</offset><text>Title:</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_3</infon><infon key="type">text</infon><offset>56</offset><text>Epigenome signatures landscaped by histone H3K9me3 are associated with the synaptic dysfunction in Alzheimer's disease</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_4</infon><infon key="type">text</infon><offset>175</offset><text>Min Young Lee, Junghee Lee, Seung Jae Hyeon, Hyesun Cho, Yu Jin Hwang,</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_5</infon><infon key="type">text</infon><offset>247</offset><text>Jong-Yeon Shin, Thor Stein, Ann C. McKee, Neil W. Kowall, Jong Il Kim,</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_6</infon><infon key="type">text</infon><offset>319</offset><text>Daehee Hwang, and Hoon Ryu</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_7</infon><infon key="type">text</infon><offset>346</offset><text>Supplementary Methods</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_8</infon><infon key="type">text</infon><offset>368</offset><text>Brain cell-type-specific designation analysis</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_9</infon><infon key="type">text</infon><offset>414</offset><text>The common genes that are landscaped by H3K9me3 were analyzed by the Molecular Signatures Database (MSiqDB) of Gene Set Enrichment Analysis (GSEA) from DMGs and DEGs [2]. We selected the Kyoto Encyclopedia of Genes and Genomes (KEGG) gene set of MSiqDB. Hierarchical clustering was performed using average linkage method of Cluster 3.0 [3].</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_10</infon><infon key="type">text</infon><offset>756</offset><text>Brain cell-type (neurons, astrocytes, oligodendrocytes, endothelial and microglia)-specific genes were computed and sorted by designating a large scale human brain single-cell RNA seq dataset [1]. Cell-type-specific genes were filtered by several criteria [4]. The filtered cell type-specific genes (1032 neurons, 191 astrocytes, 111 oligodendrocytes, 76 endothelial, 118 microglia) were sorted based on H3K9me3 occupancy (DMGs) and gene expression (DEGs).</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_11</infon><infon key="type">text</infon><offset>1215</offset><text>Chromatin immunoprecipitation (ChIP)</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_12</infon><infon key="type">text</infon><offset>1252</offset><text>ChIP for H3K9me3-DNA was performed using a CHIP assay kit (Santa Cruz) as described previously [15]. Brain tissues collected from AD patients and normal subjects were cross-linked with 1 % formaldehyde for 20 min at room temperature. The lysates were sonicated six times with each time for 30 s using Bioruptor (Diagenode Inc., NJ, USA). After centrifugation, the supernatant was diluted in CHIP dilution buffer and then incubated overnight at 4 &amp;deg;C with anti-H3K9me3 antibody. Immune complexes were recovered by the addition of 60 &amp;mu;l of salmon sperm DNA/protein A agarose-50 % slurry and incubation for 2h at 4 &amp;deg;C with rotation. The beads were pelleted and washed with low and high salt buffer and finally three times with LiCl buffer. The immune complexes were eluted by incubation for 4 h at 66 &amp;deg;C with 500 &amp;mu;l of fresh elution buffer (1 % SDS, 0.1 M NaHCO3) and 20 &amp;mu;l of 5 M NaCl. The DNA cleaned by the addition of 2 &amp;mu;l of 500 mM EDTA, 1 &amp;mu;l of 1 M Tris and 1 &amp;mu;l of proteinase K. The DNA solution is extracted with a phenol/chloroform/isoamyl alcohol mixture to remove protein contaminants, then precipitated with 100 % ethanol. After the precipitation step, the pellet was washed with 70 % ethanol and dissolved in 20 &amp;mu;l DW.</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_13</infon><infon key="type">text</infon><offset>2480</offset><text>Quantitative real-time PCR (qPCR)</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_14</infon><infon key="type">text</infon><offset>2514</offset><text>Fifty nanograms of RNA were used as a template for qPCR amplification, using SYBR Green Real-time PCR Master Mix (Toyobo, Japan) as previously described. Two-step PCR thermal cycling for DNA amplification and real-time data acquisition was performed with an ABI StepOnePlusTM Real-Time PCR System using the following cycle conditions: 95 &amp;deg;C for 1 min 1 cycle, and 95 &amp;deg;C for 15 s, followed by 60 &amp;deg;C for 1 min 40 cycles. Fluorescence data were analyzed by the ABI StepOnePlus software and expressed as CT, the number of cycles needed to generate a fluorescent signal above a predefined threshold. The ABI StepOnePlus software set baseline and threshold values. Primers were standardized in the linear range of cycles prior to onset of the plateau. The mRNA was normalized to GAPDH. The qPCR primer sequences that are used in this study, is described in Supplementary Table 9.</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_15</infon><infon key="type">text</infon><offset>3390</offset><text>ChIP-sequencing</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_16</infon><infon key="type">text</infon><offset>3406</offset><text>ChIP-seq library were constructed from the ChIP DNA samples following Illumina&rsquo;s Chip-seq sample preparation protocol. Briefly, Chip DNA was end-blunted and added with an &lsquo;A&rsquo; base such that the adaptors from Illumina with a &lsquo;T&rsquo; could ligate on the ends. 200&amp;ndash;400 bp fragments were then gel-isolated and purified. The library was amplified by 18 cycles of PCR. The resulting DNA libraries were quantified by an Agilent DNA 1000 series II assay and a Nanodrop 7500 spectrophotometer using a 1.5 &amp;mu;l aliquot diluted to 10 nM. We performed cluster generation and 36 cycles of sequencing on the Illumina cluster station and HiSeq2000 according to the manufacturer&rsquo;s instructions. Basic analyses of ChIP-seq data, such as image analysis and base calling, were performed using the Illumina&rsquo;s Genome Analysis pipeline.</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_17</infon><infon key="type">text</infon><offset>4215</offset><text>mRNA-sequencing</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_18</infon><infon key="type">text</infon><offset>4231</offset><text>We first prepared samples for mRNA-seq following the Illumina standard protocol. Briefly, 3 &amp;mu;g of total RNA from each sample was used for polyA mRNA selection using streptavidin-coated magnetic beads, followed by thermal mRNA fragmentation. The fragmented mRNA was reverse-transcribed to generate cDNA using reverse transcriptase (SuperScript II) and random primers, which was further converted into double-stranded cDNA. After an end repair process (Klenow fragment, T4 polynucleotide kinase and T4 polymerase), the resulting cDNA was finally ligated to Illumina paired end (PE) adaptors. Using a 2 % agarose gel, cDNA libraries ranging in size between 200 and 250 bp were selected, subjected to ten cycles of PCR, and then purified using the QIAquick PCR purification kit (Qiagen). The enriched libraries were diluted with Elution Buffer to a final concentration of 10 nM. Finally, 8 pM of the library in each sample was sequenced using the HiSeq2000 with 101 bp sequencing.</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_19</infon><infon key="type">text</infon><offset>5208</offset><text>Analysis of mRNA-seq data</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_20</infon><infon key="type">text</infon><offset>5234</offset><text>Adapter sequences and bases with quality scores less than 20 were trimmed using cutadapt [16]. All reads were mapped to the human reference genome (GRCh37, version 19) using TopHat (version 2.0.7,) with the default parameters [23]. Duplicated reads at the same genomic location were discarded using Picard, and the mapped reads with MAPQ&lt;5 were discarded [18]. For each gene, the number of reads in the exons were counted using R package GenomicFeatures [24]. The genes with zero counts across all samples were discarded. The read counts were normalized by the TMM method [21]. We first identified expressed genes as the ones having read counts larger than 5, which corresponded to 0.2 count per million (CPM) and log2CPM = -2.32 in our datasets, according to the instruction in the user&rsquo;s guide of edgeR package [25]. Then, the differentially expressed genes (DEGs) were identified from the expressed genes with log2CPM &gt; -2 using the two different methods, EdgeR and DESeq [22, 26]. Each method computed the significance (P-value) of a gene being differentially expressed. In each method, the DEGs were selected as the genes with P &lt; 0.05 and fold-changes &gt; a cutoff, which was determined as a minimal fold-change cutoff, the 10th percentile (1.38-fold) of the fold-change distribution obtained by performing random permutation experiments 1000 times, as previously described [27, 28]. Finally, we combined the two sets of the DEGs identified from the two methods (3290 and 1483 DEGs from EdgeR and DESeq, respectively) and used them for the following analyses.</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_21</infon><infon key="type">text</infon><offset>6798</offset><text>Western blot analysis</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_22</infon><infon key="type">text</infon><offset>6820</offset><text>Western blot was performed as previously described [12]. Thirty microgram of protein was subjected to SDS-PAGE (10%) and blotted with anti-H3K9me3 (Upstate Biotech.), anti-ESET (Santa Cruz Biotech.) antibody. Protein loading was controlled by probing for histone H3 (Upstate Biotech) or alpha-tubulin (Sigma) on the same membrane.</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_23</infon><infon key="type">text</infon><offset>7151</offset><text>Confocal microscopy</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_24</infon><infon key="type">text</infon><offset>7171</offset><text>The tissue sections were rehydrated, blocked with blocking solution (5% BSA), and incubated with anti-H3K9me3 antibody (1:200 dilutions) (Upstate Biotech.) for 24 hr as previously described [15]. After three times of washing, the slides were incubated with Cy3-conjugtared secondary antibody. The nuclei were counterstained with DAPI (4',6-diamidino-2-phenylindole). Images were analyzed using a Spinning Disk Confocal microscope (IX2-DSU, Olympus). Preabsorbtion with excess target protein or omission of primary antibody was used to demonstrate antibody specificity and background generated from the detection assay.</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_25</infon><infon key="type">text</infon><offset>7790</offset><text>Supplementary References</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_26</infon><infon key="type">text</infon><offset>7815</offset><text>1. Darmanis, S. et al., A survey of human brain transcriptome diversity at the single cell level. Proc Natl Acad Sci U S A, 2015. 112:7285-7290.</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_27</infon><infon key="type">text</infon><offset>7960</offset><text>2. Subramanian, A. et al., Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A, 2005. 102:15545-15550.</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_28</infon><infon key="type">text</infon><offset>8143</offset><text>3. de Hoon, M.J. et al., Open source clustering software. Bioinformatics, 2004. 20: 1453-1454.</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_29</infon><infon key="type">text</infon><offset>8238</offset><text>4. Wang, M. et al., Integrative network analysis of nineteen brain regions identifies molecular signatures and networks underlying selective regional vulnerability to Alzheimer's disease. Genome Med, 2016. 8:104.</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_30</infon><infon key="type">text</infon><offset>8451</offset><text>Supplementary Table 1. Information on brain tissue samples from normal subjects and AD patients.</text></passage><passage><infon key="section_type">TABLE</infon><infon key="xml"><?xml version="1.0" encoding="UTF-8"?> <table border=1><tbody><tr><td>Number</td><td>Case</td><td>Age</td><td>Sex</td><td>Braak stage</td></tr><tr><td>1</td><td>Normal</td><td>87</td><td>Female</td><td>I</td></tr><tr><td>2</td><td>Normal</td><td>88</td><td>Male</td><td>I</td></tr><tr><td>3</td><td>Normal</td><td>86</td><td>Male</td><td>II</td></tr><tr><td>4</td><td>Normal</td><td>87</td><td>Female</td><td>II</td></tr><tr><td>5</td><td>Normal</td><td>67</td><td>Male</td><td>I</td></tr><tr><td>6</td><td>Normal</td><td>82</td><td>Male</td><td>I</td></tr><tr><td>7</td><td>Normal</td><td>61</td><td>Male</td><td>I</td></tr><tr><td>8</td><td>Normal</td><td>101</td><td>Female</td><td>I</td></tr><tr><td>9</td><td>Normal</td><td>89</td><td>Male</td><td>III</td></tr><tr><td>10</td><td>Normal</td><td>68</td><td>Male</td><td>I</td></tr><tr><td>11</td><td>Normal</td><td>78</td><td>Female</td><td>I</td></tr><tr><td>12</td><td>Normal</td><td>89</td><td>Male</td><td>III</td></tr><tr><td>13</td><td>Normal</td><td>70</td><td>Male</td><td>I</td></tr><tr><td>14</td><td>Normal</td><td>82</td><td>Male</td><td>I</td></tr><tr><td>15</td><td>Normal</td><td>79</td><td>Female</td><td>I</td></tr><tr><td>16</td><td>Normal</td><td>70</td><td>Male</td><td>I</td></tr><tr><td>17</td><td>Normal</td><td>59</td><td>Male</td><td>II</td></tr><tr><td>18</td><td>Normal</td><td>80</td><td>Female</td><td>I</td></tr><tr><td>19</td><td>Normal</td><td>92</td><td>Male</td><td>I</td></tr><tr><td>20</td><td>Normal</td><td>90</td><td>Female</td><td>I</td></tr><tr><td>21</td><td>AD</td><td>85</td><td>Male</td><td>V</td></tr><tr><td>22</td><td>AD</td><td>78</td><td>Male</td><td>V</td></tr><tr><td>23</td><td>AD</td><td>80</td><td>Male</td><td>VI</td></tr><tr><td>24</td><td>AD</td><td>70</td><td>Female</td><td>VI</td></tr><tr><td>25</td><td>AD</td><td>79</td><td>Male</td><td>IV</td></tr><tr><td>26</td><td>AD</td><td>87</td><td>Female</td><td>V</td></tr><tr><td>27</td><td>AD</td><td>82</td><td>Male</td><td>V</td></tr><tr><td>28</td><td>AD</td><td>79</td><td>Female</td><td>VI</td></tr><tr><td>29</td><td>AD</td><td>70</td><td>Male</td><td>VI</td></tr><tr><td>30</td><td>AD</td><td>59</td><td>Male</td><td>VI</td></tr><tr><td>31</td><td>AD</td><td>80</td><td>Female</td><td>V</td></tr><tr><td>32</td><td>AD</td><td>92</td><td>Male</td><td>V</td></tr><tr><td>33</td><td>AD</td><td>90</td><td>Female</td><td>V</td></tr><tr><td>34</td><td>AD</td><td>100</td><td>Male</td><td>V</td></tr><tr><td>35</td><td>AD</td><td>75</td><td>Male</td><td>V</td></tr><tr><td>36</td><td>AD</td><td>83</td><td>Male</td><td>VI</td></tr><tr><td>37</td><td>AD</td><td>79</td><td>Female</td><td>VI</td></tr><tr><td>38</td><td>AD</td><td>89</td><td>Male</td><td>IV</td></tr><tr><td>39</td><td>AD</td><td>69</td><td>Male</td><td>VI</td></tr><tr><td>40</td><td>AD</td><td>79</td><td>Female</td><td>V</td></tr></tbody></table></infon><infon key="id">Table_31</infon><infon key="type">table</infon><offset>8548</offset><text>Number
Case
Age
Sex
Braak stage
1
Normal
87
Female
I
2
Normal
88
Male
I
3
Normal
86
Male
II
4
Normal
87
Female
II
5
Normal
67
Male
I
6
Normal
82
Male
I
7
Normal
61
Male
I
8
Normal
101
Female
I
9
Normal
89
Male
III
10
Normal
68
Male
I
11
Normal
78
Female
I
12
Normal
89
Male
III
13
Normal
70
Male
I
14
Normal
82
Male
I
15
Normal
79
Female
I
16
Normal
70
Male
I
17
Normal
59
Male
II
18
Normal
80
Female
I
19
Normal
92
Male
I
20
Normal
90
Female
I
21
AD
85
Male
V
22
AD
78
Male
V
23
AD
80
Male
VI
24
AD
70
Female
VI
25
AD
79
Male
IV
26
AD
87
Female
V
27
AD
82
Male
V
28
AD
79
Female
VI
29
AD
70
Male
VI
30
AD
59
Male
VI
31
AD
80
Female
V
32
AD
92
Male
V
33
AD
90
Female
V
34
AD
100
Male
V
35
AD
75
Male
V
36
AD
83
Male
VI
37
AD
79
Female
VI
38
AD
89
Male
IV
39
AD
69
Male
VI
40
AD
79
Female
V
</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_32</infon><infon key="type">text</infon><offset>9626</offset><text>Supplementary Table 2. Summary of H3K9me3 ChIP-sequencing alignment. AD, Alzheimer&rsquo;s disease patient; C, control normal subject.</text></passage><passage><infon key="section_type">TABLE</infon><infon key="xml"><?xml version="1.0" encoding="UTF-8"?> <table border=1><tbody><tr><td>Case</td><td>Total reads</td><td>Filtered</td><td>Used</td><td>Aligned</td><td>Uniquely aligned reads</td><td>Alignment ratio</td><td>Depth (fold)</td></tr><tr><td>AD1</td><td>49,822,698</td><td>4,186,387</td><td>45,636,311</td><td>24,964,206</td><td>17,534,648</td><td>0.55</td><td>0.51</td></tr><tr><td>AD2</td><td>45,113,702</td><td>5,425,981</td><td>39,687,721</td><td>22,793,875</td><td>16,659,985</td><td>0.57</td><td>0.52</td></tr><tr><td>AD3</td><td>53,280,572</td><td>5,698,574</td><td>47,581,998</td><td>36,671,192</td><td>28,280,368</td><td>0.77</td><td>0.89</td></tr><tr><td>AD4</td><td>43,906,144</td><td>5,989,777</td><td>37,916,367</td><td>23,702,350</td><td>17,392,118</td><td>0.63</td><td>0.57</td></tr><tr><td>AD5</td><td>83,255,608</td><td>6,717,509</td><td>76,538,099</td><td>69,711,657</td><td>57,005,146</td><td>0.91</td><td>2.00</td></tr><tr><td>AD6</td><td>51,795,958</td><td>4,770,452</td><td>47,025,506</td><td>35,977,097</td><td>27,486,222</td><td>0.77</td><td>0.90</td></tr><tr><td>C1</td><td>35,856,132</td><td>4,589,308</td><td>31,266,824</td><td>19,235,296</td><td>13,082,606</td><td>0.62</td><td>0.40</td></tr><tr><td>C2</td><td>51,522,722</td><td>5,482,295</td><td>46,040,427</td><td>35,107,493</td><td>26,445,487</td><td>0.76</td><td>0.86</td></tr><tr><td>C3</td><td>27,902,276</td><td>5,552,044</td><td>22,350,232</td><td>14,795,547</td><td>10,473,113</td><td>0.66</td><td>0.34</td></tr><tr><td>C4</td><td>60,184,128</td><td>5,522,863</td><td>54,661,265</td><td>41,810,285</td><td>32,693,238</td><td>0.76</td><td>1.03</td></tr><tr><td>C5</td><td>30,778,772</td><td>3,032,163</td><td>27,746,609</td><td>23,064,566</td><td>17,877,738</td><td>0.83</td><td>0.63</td></tr><tr><td>C6</td><td>43,931,796</td><td>3,918,104</td><td>40,013,692</td><td>31,535,082</td><td>24,724,978</td><td>0.79</td><td>0.80</td></tr></tbody></table></infon><infon key="id">Table_33</infon><infon key="type">table</infon><offset>9755</offset><text>Case
Total reads
Filtered
Used
Aligned
Uniquely aligned reads
Alignment ratio
Depth (fold)
AD1
49,822,698
4,186,387
45,636,311
24,964,206
17,534,648
0.55
0.51
AD2
45,113,702
5,425,981
39,687,721
22,793,875
16,659,985
0.57
0.52
AD3
53,280,572
5,698,574
47,581,998
36,671,192
28,280,368
0.77
0.89
AD4
43,906,144
5,989,777
37,916,367
23,702,350
17,392,118
0.63
0.57
AD5
83,255,608
6,717,509
76,538,099
69,711,657
57,005,146
0.91
2.00
AD6
51,795,958
4,770,452
47,025,506
35,977,097
27,486,222
0.77
0.90
C1
35,856,132
4,589,308
31,266,824
19,235,296
13,082,606
0.62
0.40
C2
51,522,722
5,482,295
46,040,427
35,107,493
26,445,487
0.76
0.86
C3
27,902,276
5,552,044
22,350,232
14,795,547
10,473,113
0.66
0.34
C4
60,184,128
5,522,863
54,661,265
41,810,285
32,693,238
0.76
1.03
C5
30,778,772
3,032,163
27,746,609
23,064,566
17,877,738
0.83
0.63
C6
43,931,796
3,918,104
40,013,692
31,535,082
24,724,978
0.79
0.80
</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_34</infon><infon key="type">text</infon><offset>10787</offset><text>Supplementary Table 3. H3K9me3 occupancy in the promoter, intergenic, and gene body regions. The gene body occupancy was further divided by CDS, UTR, and introns. AD, Alzheimer&rsquo;s disease patient; C, control normal subject.</text></passage><passage><infon key="section_type">TABLE</infon><infon key="xml"><?xml version="1.0" encoding="UTF-8"?> <table border=1><tbody><tr><td>Case</td><td>%Promoter</td><td>% Intergenic</td><td>%Gene body</td><td>%CDS</td><td>%UTR</td><td>%Intron</td></tr><tr><td>AD1</td><td>2.27</td><td>62.76</td><td>34.97</td><td>2.43</td><td>2.63</td><td>94.94</td></tr><tr><td>AD2</td><td>2.52</td><td>58.47</td><td>39.02</td><td>2.43</td><td>2.71</td><td>94.86</td></tr><tr><td>AD3</td><td>2.63</td><td>57.63</td><td>39.74</td><td>2.42</td><td>2.80</td><td>94.77</td></tr><tr><td>AD4</td><td>2.55</td><td>58.71</td><td>38.75</td><td>2.45</td><td>2.74</td><td>94.81</td></tr><tr><td>AD5</td><td>2.90</td><td>54.42</td><td>42.68</td><td>2.48</td><td>2.90</td><td>94.61</td></tr><tr><td>AD6</td><td>2.27</td><td>59.66</td><td>38.07</td><td>2.25</td><td>2.65</td><td>95.10</td></tr><tr><td>C1</td><td>2.36</td><td>60.15</td><td>37.48</td><td>2.62</td><td>2.66</td><td>94.71</td></tr><tr><td>C2</td><td>2.40</td><td>58.37</td><td>39.22</td><td>2.53</td><td>2.72</td><td>94.75</td></tr><tr><td>C3</td><td>2.32</td><td>59.15</td><td>38.52</td><td>2.49</td><td>2.67</td><td>94.84</td></tr><tr><td>C4</td><td>2.69</td><td>56.20</td><td>41.10</td><td>2.54</td><td>2.82</td><td>94.64</td></tr><tr><td>C5</td><td>2.75</td><td>56.99</td><td>40.26</td><td>2.72</td><td>2.89</td><td>94.39</td></tr><tr><td>C6</td><td>2.59</td><td>56.79</td><td>40.62</td><td>2.59</td><td>2.80</td><td>94.61</td></tr></tbody></table></infon><infon key="id">Table_35</infon><infon key="type">table</infon><offset>11010</offset><text>Case
%Promoter
% Intergenic
%Gene body
%CDS
%UTR
%Intron
AD1
2.27
62.76
34.97
2.43
2.63
94.94
AD2
2.52
58.47
39.02
2.43
2.71
94.86
AD3
2.63
57.63
39.74
2.42
2.80
94.77
AD4
2.55
58.71
38.75
2.45
2.74
94.81
AD5
2.90
54.42
42.68
2.48
2.90
94.61
AD6
2.27
59.66
38.07
2.25
2.65
95.10
C1
2.36
60.15
37.48
2.62
2.66
94.71
C2
2.40
58.37
39.22
2.53
2.72
94.75
C3
2.32
59.15
38.52
2.49
2.67
94.84
C4
2.69
56.20
41.10
2.54
2.82
94.64
C5
2.75
56.99
40.26
2.72
2.89
94.39
C6
2.59
56.79
40.62
2.59
2.80
94.61
</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_36</infon><infon key="type">text</infon><offset>11623</offset><text>Supplementary Table 4. DMGs identified by MACS and EdgeR. EdgeR-P and GB represent the DMGs whose promoters or gene bodies were differentially marked between the cortex of AD patients and normal subjects (Please confer an attached excel file including Supplementary Table 4 and 7).</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_37</infon><infon key="type">text</infon><offset>11905</offset><text>Supplementary Table 5. GOBPs represented by the DMGs. 'Increased' and 'Decreased' represent the GOBPs represented by the genes with increased and decreased H3K9me3 occupancy in the promoter region of gene, respectively. 'Count' means the number of the genes involved in the corresponding GOBP. Such genes are listed.</text></passage><passage><infon key="section_type">TABLE</infon><infon key="xml"><?xml version="1.0" encoding="UTF-8"?> <table border=1><tbody><tr><td></td><td>Term_ID</td><td>Description</td><td>Count</td><td>P-value</td><td>Genes</td></tr><tr><td>Increased</td><td>GO:0050877</td><td>neurological system process</td><td>61</td><td>0.00</td><td>OR1A2, LXN, MYO7A, OR11A1, OR11H12, KIFC3, CTNNB1, CRYGA, FOS, SPRY2, CRYGB, BDNF, SLC1A3, OR6C1, OR4C11, OR6P1, MKKS, SLC22A3, IL1B, CDH23, OR7A10, OR4F17, OR4M1, OR1D5, CBLN1, OR5V1, UBC, ABAT, OR4N2, PRKCZ, PCDHB14, COL2A1, RIMS1, OR4F4, PDE6B, MUSK, OR10G8, TAS2R46, AGT, DMD, AGRN, OR51V1, COL18A1, OR5P3, GABRA2, OR5M10, DLGAP2, OR5K2, OR10H1, SOD1, OR10H5, OR10H3, GABARAP, GJB2, CACNA2D4, OR4F6, EYS, OR3A2, OR51A2, OR51A4, WNT7A</td></tr><tr><td></td><td>GO:0050890</td><td>cognition</td><td>47</td><td>0.00</td><td>PRKCZ, OR1A2, LXN, MYO7A, OR11A1, COL2A1, OR11H12, RIMS1, OR4F4, KIFC3, CRYGA, SPRY2, FOS, CRYGB, PDE6B, BDNF, OR10G8, SLC1A3, TAS2R46, OR6C1, OR4C11, OR6P1, MKKS, IL1B, OR7A10, CDH23, OR51V1, COL18A1, OR5P3, OR5M10, OR5K2, OR4F17, OR10H1, OR4M1, OR10H5, SOD1, OR1D5, OR10H3, GJB2, CACNA2D4, EYS, OR4F6, OR5V1, OR3A2, OR51A2, OR4N2, OR51A4</td></tr><tr><td></td><td>GO:0010941</td><td>regulation of cell death</td><td>39</td><td>0.01</td><td>DLC1, PRKCZ, HTATIP2, C6, IL19, RAG1, RRAGA, SOX4, COL2A1, PF4, ASNS, FOXO3, VDR, BDNF, AGT, IL1B, TOP2A, COL18A1, PGAP2, CARD8, ADAMTS20, MADD, MSH2, TGFBR1, RXRA, KLF10, BCL2A1, STRADB, SOD1, ADRB2, CUL4A, UBC, NLRP12, SERPINB2, ADAM17, ID3, NGFR, BMP7, LRRK2</td></tr><tr><td></td><td>GO:0010604</td><td>positive regulation of macromolecule metabolic process</td><td>37</td><td>0.05</td><td>DLC1, GLIS3, THRA, FOXA2, SOX4, PF4, FOXO3, RORA, CTNNB1, FOS, AGT, PSMB2, HINFP, IL1B, AGRN, NR2F2, KDM5A, SUPT5H, TGFBR1, TP53BP1, RXRA, FOXA1, MED14, UBE2N, ADRB2, PSMC6, ATF4, PKNOX1, PSMA5, IRF6, MED17, ETS2, UBC, FOXE1, ADAM17, BMP7, LRRK2</td></tr><tr><td></td><td>GO:0007155</td><td>cell adhesion</td><td>33</td><td>0.02</td><td>DLC1, PCDHA8, THRA, PCDHB14, CTNND1, ARF6, COL2A1, CRNN, PCDHGA4, CLDN12, CTNNB1, CDH6, LAMB3, AGT, PCDHA10, ANGPTL3, MLLT4, DSCAM, CDH23, COL18A1, SELP, PCDHGA10, CLCA2, PCDHGA11, PCDH9, AJAP1, NID2, MUC4, SIGLEC6, ITGB1BP1, CDON, TROAP, ADAM17</td></tr><tr><td></td><td>GO:0022610</td><td>biological adhesion</td><td>33</td><td>0.02</td><td>DLC1, PCDHA8, THRA, PCDHB14, CTNND1, ARF6, COL2A1, CRNN, PCDHGA4, CLDN12, CTNNB1, CDH6, LAMB3, AGT, PCDHA10, ANGPTL3, MLLT4, DSCAM, CDH23, COL18A1, SELP, PCDHGA10, CLCA2, PCDHGA11, PCDH9, AJAP1, NID2, MUC4, SIGLEC6, ITGB1BP1, CDON, TROAP, ADAM17</td></tr><tr><td></td><td>GO:0007267</td><td>cell-cell signaling</td><td>32</td><td>0.00</td><td>CXCL5, IL18, LTBP4, PCDHB14, CCL8, RIMS1, EPHB1, CTNNB1, PGR, SPRY2, MUSK, BDNF, SLC1A3, IFNA7, AGT, DMD, SLC22A3, IL1B, AGRN, MLLT4, GABRA2, DLGAP2, NUDT3, KLF10, FZD1, GABARAP, GJB2, CBLN1, SIGLEC6, UBC, ABAT, WNT7A</td></tr><tr><td></td><td>GO:0032989</td><td>cellular component morphogenesis</td><td>24</td><td>0.00</td><td>COL18A1, RXRA, MYO7A, LIFR, RPL24, STRADB, SOD1, EPHB1, CTNNB1, SLITRK1, CRYGB, SLITRK4, BDNF, SLC1A3, DMD, DLX5, UBC, GBX2, MKKS, NGFR, BMP7, DCLK1, DSCAM, CDH23</td></tr><tr><td></td><td>GO:0030030</td><td>cell projection organization</td><td>21</td><td>0.01</td><td>RXRA, MYO7A, LIFR, ARF6, RPL24, SOD1, PRKG1, EPHB1, SLITRK1, BDNF, SLITRK4, DLX5, DMD, UBC, GBX2, MKKS, NGFR, BMP7, DCLK1, DSCAM, CDH23</td></tr><tr><td></td><td>GO:0009628</td><td>response to abiotic stimulus</td><td>20</td><td>0.02</td><td>COL18A1, TRPC3, LXN, MSH2, IL18, RBM3, TGFBR1, CRNN, SOD1, PDE6B, FOS, ADRB2, SLC1A3, GTF2H2C, AGT, DDB2, MKKS, IL1B, NGFR, IGFBP2</td></tr><tr><td></td><td>GO:0044092</td><td>negative regulation of molecular function</td><td>20</td><td>0.01</td><td>CAST, PRKCZ, THRA, NF2, ADCY5, GABBR1, RAG1, PDCD4, SPRY2, PSMC6, ADRB2, PSMA5, HEXIM1, PSMB2, GADD45G, UBC, IL1B, ID3, ANGPTL3, GADD45B</td></tr><tr><td></td><td>GO:0051726</td><td>regulation of cell cycle</td><td>19</td><td>0.02</td><td>MSH2, MADD, SIPA1, DBC1, RPL24, ASNS, ATR, PDCD4, HEXIM1, GADD45G, HINFP, IL1B, ADAM17, CDK5RAP3, ID3, NGFR, GADD45B, BMP7, RAD17</td></tr><tr><td></td><td>GO:0007423</td><td>sensory organ development</td><td>18</td><td>0.00</td><td>MYO7A, RPL24, COL2A1, SOD1, EPHB1, CTNNB1, HESX1, CRYGA, CRYGB, SPRY2, BDNF, PKNOX1, DLX5, GBX2, MAB21L1, BMP7, DSCAM, CDH23</td></tr><tr><td></td><td>GO:0001501</td><td>skeletal system development</td><td>17</td><td>0.04</td><td>THRA, LGALS3, TGFBR1, KLF10, GABBR1, COL2A1, CTNNB1, VDR, COL9A2, HOXB7, KAZALD1, DLX5, ETS2, HOXC5, BMP7, WNT7A, TLL1</td></tr><tr><td></td><td>GO:0043086</td><td>negative regulation of catalytic activity</td><td>17</td><td>0.01</td><td>CAST, PRKCZ, NF2, ADCY5, GABBR1, RAG1, PDCD4, SPRY2, PSMC6, PSMA5, HEXIM1, PSMB2, GADD45G, UBC, IL1B, ANGPTL3, GADD45B</td></tr><tr><td></td><td>GO:0051094</td><td>positive regulation of developmental process</td><td>17</td><td>0.01</td><td>SH3PXD2B, FOXA2, ADAMTS20, KLF10, FOXA1, PF4, FOXO3, CTNNB1, BDNF, ADRB2, AGT, DLX5, IL1B, NGFR, ANGPTL3, BMP7, WNT7A</td></tr><tr><td></td><td>GO:0060429</td><td>epithelium development</td><td>17</td><td>0.00</td><td>COL18A1, DLC1, FOXA2, FOXA1, FZD1, CTNNB1, PGR, LCE1E, IRF6, AGT, DLX5, SPRR1B, LCE1D, MKKS, ID3, NR2F2, BMP7</td></tr><tr><td></td><td>GO:0001944</td><td>vasculature development</td><td>16</td><td>0.01</td><td>COL18A1, SELP, HTATIP2, IL18, TGFBR1, NCL, CTNNB1, CRKL, PKNOX1, DLL4, AGT, ECSCR, GBX2, IL1B, ANGPTL3, NR2F2</td></tr><tr><td></td><td>GO:0031399</td><td>regulation of protein modification process</td><td>16</td><td>0.05</td><td>DLC1, PRKCZ, NF2, TGFBR1, PDCD4, UBE2N, PSMC6, PSMA5, AGT, PSMB2, UBC, NLRP12, IL1B, ADAM17, BMP7, LRRK2</td></tr><tr><td></td><td>GO:0048858</td><td>cell projection morphogenesis</td><td>16</td><td>0.01</td><td>RXRA, LIFR, RPL24, EPHB1, SLITRK1, BDNF, SLITRK4, DLX5, DMD, UBC, GBX2, MKKS, NGFR, BMP7, DCLK1, DSCAM</td></tr><tr><td></td><td>GO:0003006</td><td>developmental process involved in reproduction</td><td>15</td><td>0.04</td><td>MSH2, SOX3, FOXA1, FOXO3, SOD1, GJB2, CDH6, PGR, VDR, AGT, PIWIL1, NKX3-1, MKKS, HSD17B4, WNT7A</td></tr><tr><td></td><td>GO:0051240</td><td>positive regulation of multicellular organismal process</td><td>15</td><td>0.02</td><td>PRKCZ, CARD8, IL18, PF4, SOD1, ADRB2, SLC1A3, AGT, UBC, NLRP12, TBXA2R, IL1B, ADAM17, BMP7, AGPAT2</td></tr><tr><td></td><td>GO:0007398</td><td>ectoderm development</td><td>13</td><td>0.02</td><td>FOXA2, NF2, CTNNB1, C1ORF68, LAMB3, LCE1E, IRF6, SPRR1B, LCE1D, FOXE1, NGFR, WNT7A, NSDHL</td></tr><tr><td></td><td>GO:0048568</td><td>embryonic organ development</td><td>13</td><td>0.01</td><td>MYO7A, TGFBR1, SPINT1, COL2A1, SOD1, HESX1, SPRY2, HOXB7, DLX5, FOXE1, GBX2, BMP7, CDH23</td></tr><tr><td></td><td>GO:0043062</td><td>extracellular structure organization</td><td>12</td><td>0.01</td><td>COL18A1, MUSK, LGALS3, ADAMTS20, KAZALD1, AGT, TGFBR1, PCDHB14, COL2A1, AGRN, WNT7A, CTNNB1</td></tr><tr><td></td><td>GO:0007548</td><td>sex differentiation</td><td>10</td><td>0.05</td><td>PGR, MSH2, AGT, MKKS, HSD17B4, FOXO3, SOD1, WNT7A, CDH6, GJB2</td></tr><tr><td></td><td>GO:0009266</td><td>response to temperature stimulus</td><td>10</td><td>0.00</td><td>FOS, ADRB2, LXN, RBM3, IL18, AGT, IL1B, NGFR, CRNN, SOD1</td></tr><tr><td></td><td>GO:0035239</td><td>tube morphogenesis</td><td>10</td><td>0.02</td><td>DLC1, SPRY2, FOXA2, AGT, FOXA1, GBX2, NKX3-1, MKKS, BMP7, CTNNB1</td></tr><tr><td></td><td>GO:0001763</td><td>morphogenesis of a branching structure</td><td>9</td><td>0.00</td><td>SPRY2, FOXA2, AGT, FOXA1, GBX2, NKX3-1, SPINT1, BMP7, CTNNB1</td></tr><tr><td></td><td>GO:0001819</td><td>positive regulation of cytokine production</td><td>9</td><td>0.01</td><td>CARD8, IL18, AGT, NLRP12, ADAM17, IL1B, PF4, SOD1, AGPAT2</td></tr><tr><td></td><td>GO:0043583</td><td>ear development</td><td>9</td><td>0.01</td><td>HESX1, SPRY2, BDNF, DLX5, MYO7A, GBX2, COL2A1, SOD1, CDH23</td></tr><tr><td></td><td>GO:0006414</td><td>translational elongation</td><td>8</td><td>0.04</td><td>RPS25, SNORA7A, RPS29, RPL9, UBC, RPL24, RPL7A, RPL10A</td></tr><tr><td></td><td>GO:0007605</td><td>sensory perception of sound</td><td>8</td><td>0.03</td><td>SPRY2, SLC1A3, MYO7A, MKKS, COL2A1, SOD1, CDH23, GJB2</td></tr><tr><td></td><td>GO:0050954</td><td>sensory perception of mechanical stimulus</td><td>8</td><td>0.04</td><td>SPRY2, SLC1A3, MYO7A, MKKS, COL2A1, SOD1, CDH23, GJB2</td></tr><tr><td></td><td>GO:0009409</td><td>response to cold</td><td>5</td><td>0.00</td><td>FOS, ADRB2, RBM3, IL18, AGT</td></tr><tr><td></td><td>GO:0021675</td><td>nerve development</td><td>5</td><td>0.01</td><td>BDNF, SLC1A3, RPL24, NGFR, EPHB1</td></tr><tr><td>Decreased</td><td>GO:0050890</td><td>cognition</td><td>39</td><td>0.01</td><td>OR51D1, OBP2A, OR8H3, CACNB2, TAS1R3, TIMM13, COMT, OR10G2, RIMS1, OR4F3, OR2V2, CALCA, PRKAR2B, CRYGC, BEST1, OR7G3, MCOLN3, OR8A1, IMPDH1, OR51V1, S100P, OR2AG2, OR5M10, MYO3A, FSCN2, HTT, OR8G2, OR4M2, OR52E4, PDE6G, VSX1, RGS9BP, SFRP5, TAS2R16, CRH, OR6V1, OR4N2, WDR1, CACNA1C</td></tr><tr><td></td><td>GO:0007600</td><td>sensory perception</td><td>33</td><td>0.04</td><td>OR51D1, OBP2A, OR8H3, CACNB2, TAS1R3, TIMM13, OR10G2, RIMS1, OR4F3, OR2V2, CALCA, CRYGC, OR7G3, BEST1, MCOLN3, OR8A1, IMPDH1, OR51V1, OR2AG2, OR5M10, MYO3A, FSCN2, OR8G2, OR4M2, OR52E4, PDE6G, VSX1, RGS9BP, SFRP5, TAS2R16, OR6V1, OR4N2, WDR1</td></tr><tr><td></td><td>GO:0010629</td><td>negative regulation of gene expression</td><td>25</td><td>0.01</td><td>BCLAF1, CBX2, PDX1, TNFRSF4, CALCA, MEIS2, WWP2, SND1, DDX20, NRG1, NR2F2, ZNF423, DMBX1, ZNF593, EHMT1, VHL, ARID5B, TP53, FOSB, SIRT7, MBD2, FOXP1, BRCA1, SIRT3, IRF7</td></tr><tr><td></td><td>GO:0006259</td><td>DNA metabolic process</td><td>23</td><td>0.03</td><td>EXO1, RBBP4, UVRAG, TP53, PAPD5, BRCA1, FOXP1, GTF2H2, GLRX2, ATRX, POLD3, CCDC111, DNASE1, FANCM, CRY2, CSNK1E, KRT7, PSIP1, TOP3A, PMS2CL, FANCA, DNAJA3, REPIN1</td></tr><tr><td></td><td>GO:0010817</td><td>regulation of hormone levels</td><td>11</td><td>0.01</td><td>UGT1A8, LY6E, HTT, GHRH, CHST8, CYP26B1, CRH, COMT, PDX1, CACNA1C, BCO2</td></tr><tr><td></td><td>GO:0010639</td><td>negative regulation of organelle organization</td><td>7</td><td>0.03</td><td>TRIOBP, ARHGAP6, TRIM54, BUB1, ADD2, BRCA1, HDAC6</td></tr><tr><td></td><td>GO:0009914</td><td>hormone transport</td><td>5</td><td>0.05</td><td>LY6E, HTT, GHRH, PDX1, CACNA1C</td></tr></tbody></table></infon><infon key="id">Table_38</infon><infon key="type">table</infon><offset>12223</offset><text>
Term_ID
Description
Count
P-value
Genes
Increased
GO:0050877
neurological system process
61
0.00
OR1A2, LXN, MYO7A, OR11A1, OR11H12, KIFC3, CTNNB1, CRYGA, FOS, SPRY2, CRYGB, BDNF, SLC1A3, OR6C1, OR4C11, OR6P1, MKKS, SLC22A3, IL1B, CDH23, OR7A10, OR4F17, OR4M1, OR1D5, CBLN1, OR5V1, UBC, ABAT, OR4N2, PRKCZ, PCDHB14, COL2A1, RIMS1, OR4F4, PDE6B, MUSK, OR10G8, TAS2R46, AGT, DMD, AGRN, OR51V1, COL18A1, OR5P3, GABRA2, OR5M10, DLGAP2, OR5K2, OR10H1, SOD1, OR10H5, OR10H3, GABARAP, GJB2, CACNA2D4, OR4F6, EYS, OR3A2, OR51A2, OR51A4, WNT7A
GO:0050890
cognition
47
0.00
PRKCZ, OR1A2, LXN, MYO7A, OR11A1, COL2A1, OR11H12, RIMS1, OR4F4, KIFC3, CRYGA, SPRY2, FOS, CRYGB, PDE6B, BDNF, OR10G8, SLC1A3, TAS2R46, OR6C1, OR4C11, OR6P1, MKKS, IL1B, OR7A10, CDH23, OR51V1, COL18A1, OR5P3, OR5M10, OR5K2, OR4F17, OR10H1, OR4M1, OR10H5, SOD1, OR1D5, OR10H3, GJB2, CACNA2D4, EYS, OR4F6, OR5V1, OR3A2, OR51A2, OR4N2, OR51A4
GO:0010941
regulation of cell death
39
0.01
DLC1, PRKCZ, HTATIP2, C6, IL19, RAG1, RRAGA, SOX4, COL2A1, PF4, ASNS, FOXO3, VDR, BDNF, AGT, IL1B, TOP2A, COL18A1, PGAP2, CARD8, ADAMTS20, MADD, MSH2, TGFBR1, RXRA, KLF10, BCL2A1, STRADB, SOD1, ADRB2, CUL4A, UBC, NLRP12, SERPINB2, ADAM17, ID3, NGFR, BMP7, LRRK2
GO:0010604
positive regulation of macromolecule metabolic process
37
0.05
DLC1, GLIS3, THRA, FOXA2, SOX4, PF4, FOXO3, RORA, CTNNB1, FOS, AGT, PSMB2, HINFP, IL1B, AGRN, NR2F2, KDM5A, SUPT5H, TGFBR1, TP53BP1, RXRA, FOXA1, MED14, UBE2N, ADRB2, PSMC6, ATF4, PKNOX1, PSMA5, IRF6, MED17, ETS2, UBC, FOXE1, ADAM17, BMP7, LRRK2
GO:0007155
cell adhesion
33
0.02
DLC1, PCDHA8, THRA, PCDHB14, CTNND1, ARF6, COL2A1, CRNN, PCDHGA4, CLDN12, CTNNB1, CDH6, LAMB3, AGT, PCDHA10, ANGPTL3, MLLT4, DSCAM, CDH23, COL18A1, SELP, PCDHGA10, CLCA2, PCDHGA11, PCDH9, AJAP1, NID2, MUC4, SIGLEC6, ITGB1BP1, CDON, TROAP, ADAM17
GO:0022610
biological adhesion
33
0.02
DLC1, PCDHA8, THRA, PCDHB14, CTNND1, ARF6, COL2A1, CRNN, PCDHGA4, CLDN12, CTNNB1, CDH6, LAMB3, AGT, PCDHA10, ANGPTL3, MLLT4, DSCAM, CDH23, COL18A1, SELP, PCDHGA10, CLCA2, PCDHGA11, PCDH9, AJAP1, NID2, MUC4, SIGLEC6, ITGB1BP1, CDON, TROAP, ADAM17
GO:0007267
cell-cell signaling
32
0.00
CXCL5, IL18, LTBP4, PCDHB14, CCL8, RIMS1, EPHB1, CTNNB1, PGR, SPRY2, MUSK, BDNF, SLC1A3, IFNA7, AGT, DMD, SLC22A3, IL1B, AGRN, MLLT4, GABRA2, DLGAP2, NUDT3, KLF10, FZD1, GABARAP, GJB2, CBLN1, SIGLEC6, UBC, ABAT, WNT7A
GO:0032989
cellular component morphogenesis
24
0.00
COL18A1, RXRA, MYO7A, LIFR, RPL24, STRADB, SOD1, EPHB1, CTNNB1, SLITRK1, CRYGB, SLITRK4, BDNF, SLC1A3, DMD, DLX5, UBC, GBX2, MKKS, NGFR, BMP7, DCLK1, DSCAM, CDH23
GO:0030030
cell projection organization
21
0.01
RXRA, MYO7A, LIFR, ARF6, RPL24, SOD1, PRKG1, EPHB1, SLITRK1, BDNF, SLITRK4, DLX5, DMD, UBC, GBX2, MKKS, NGFR, BMP7, DCLK1, DSCAM, CDH23
GO:0009628
response to abiotic stimulus
20
0.02
COL18A1, TRPC3, LXN, MSH2, IL18, RBM3, TGFBR1, CRNN, SOD1, PDE6B, FOS, ADRB2, SLC1A3, GTF2H2C, AGT, DDB2, MKKS, IL1B, NGFR, IGFBP2
GO:0044092
negative regulation of molecular function
20
0.01
CAST, PRKCZ, THRA, NF2, ADCY5, GABBR1, RAG1, PDCD4, SPRY2, PSMC6, ADRB2, PSMA5, HEXIM1, PSMB2, GADD45G, UBC, IL1B, ID3, ANGPTL3, GADD45B
GO:0051726
regulation of cell cycle
19
0.02
MSH2, MADD, SIPA1, DBC1, RPL24, ASNS, ATR, PDCD4, HEXIM1, GADD45G, HINFP, IL1B, ADAM17, CDK5RAP3, ID3, NGFR, GADD45B, BMP7, RAD17
GO:0007423
sensory organ development
18
0.00
MYO7A, RPL24, COL2A1, SOD1, EPHB1, CTNNB1, HESX1, CRYGA, CRYGB, SPRY2, BDNF, PKNOX1, DLX5, GBX2, MAB21L1, BMP7, DSCAM, CDH23
GO:0001501
skeletal system development
17
0.04
THRA, LGALS3, TGFBR1, KLF10, GABBR1, COL2A1, CTNNB1, VDR, COL9A2, HOXB7, KAZALD1, DLX5, ETS2, HOXC5, BMP7, WNT7A, TLL1
GO:0043086
negative regulation of catalytic activity
17
0.01
CAST, PRKCZ, NF2, ADCY5, GABBR1, RAG1, PDCD4, SPRY2, PSMC6, PSMA5, HEXIM1, PSMB2, GADD45G, UBC, IL1B, ANGPTL3, GADD45B
GO:0051094
positive regulation of developmental process
17
0.01
SH3PXD2B, FOXA2, ADAMTS20, KLF10, FOXA1, PF4, FOXO3, CTNNB1, BDNF, ADRB2, AGT, DLX5, IL1B, NGFR, ANGPTL3, BMP7, WNT7A
GO:0060429
epithelium development
17
0.00
COL18A1, DLC1, FOXA2, FOXA1, FZD1, CTNNB1, PGR, LCE1E, IRF6, AGT, DLX5, SPRR1B, LCE1D, MKKS, ID3, NR2F2, BMP7
GO:0001944
vasculature development
16
0.01
COL18A1, SELP, HTATIP2, IL18, TGFBR1, NCL, CTNNB1, CRKL, PKNOX1, DLL4, AGT, ECSCR, GBX2, IL1B, ANGPTL3, NR2F2
GO:0031399
regulation of protein modification process
16
0.05
DLC1, PRKCZ, NF2, TGFBR1, PDCD4, UBE2N, PSMC6, PSMA5, AGT, PSMB2, UBC, NLRP12, IL1B, ADAM17, BMP7, LRRK2
GO:0048858
cell projection morphogenesis
16
0.01
RXRA, LIFR, RPL24, EPHB1, SLITRK1, BDNF, SLITRK4, DLX5, DMD, UBC, GBX2, MKKS, NGFR, BMP7, DCLK1, DSCAM
GO:0003006
developmental process involved in reproduction
15
0.04
MSH2, SOX3, FOXA1, FOXO3, SOD1, GJB2, CDH6, PGR, VDR, AGT, PIWIL1, NKX3-1, MKKS, HSD17B4, WNT7A
GO:0051240
positive regulation of multicellular organismal process
15
0.02
PRKCZ, CARD8, IL18, PF4, SOD1, ADRB2, SLC1A3, AGT, UBC, NLRP12, TBXA2R, IL1B, ADAM17, BMP7, AGPAT2
GO:0007398
ectoderm development
13
0.02
FOXA2, NF2, CTNNB1, C1ORF68, LAMB3, LCE1E, IRF6, SPRR1B, LCE1D, FOXE1, NGFR, WNT7A, NSDHL
GO:0048568
embryonic organ development
13
0.01
MYO7A, TGFBR1, SPINT1, COL2A1, SOD1, HESX1, SPRY2, HOXB7, DLX5, FOXE1, GBX2, BMP7, CDH23
GO:0043062
extracellular structure organization
12
0.01
COL18A1, MUSK, LGALS3, ADAMTS20, KAZALD1, AGT, TGFBR1, PCDHB14, COL2A1, AGRN, WNT7A, CTNNB1
GO:0007548
sex differentiation
10
0.05
PGR, MSH2, AGT, MKKS, HSD17B4, FOXO3, SOD1, WNT7A, CDH6, GJB2
GO:0009266
response to temperature stimulus
10
0.00
FOS, ADRB2, LXN, RBM3, IL18, AGT, IL1B, NGFR, CRNN, SOD1
GO:0035239
tube morphogenesis
10
0.02
DLC1, SPRY2, FOXA2, AGT, FOXA1, GBX2, NKX3-1, MKKS, BMP7, CTNNB1
GO:0001763
morphogenesis of a branching structure
9
0.00
SPRY2, FOXA2, AGT, FOXA1, GBX2, NKX3-1, SPINT1, BMP7, CTNNB1
GO:0001819
positive regulation of cytokine production
9
0.01
CARD8, IL18, AGT, NLRP12, ADAM17, IL1B, PF4, SOD1, AGPAT2
GO:0043583
ear development
9
0.01
HESX1, SPRY2, BDNF, DLX5, MYO7A, GBX2, COL2A1, SOD1, CDH23
GO:0006414
translational elongation
8
0.04
RPS25, SNORA7A, RPS29, RPL9, UBC, RPL24, RPL7A, RPL10A
GO:0007605
sensory perception of sound
8
0.03
SPRY2, SLC1A3, MYO7A, MKKS, COL2A1, SOD1, CDH23, GJB2
GO:0050954
sensory perception of mechanical stimulus
8
0.04
SPRY2, SLC1A3, MYO7A, MKKS, COL2A1, SOD1, CDH23, GJB2
GO:0009409
response to cold
5
0.00
FOS, ADRB2, RBM3, IL18, AGT
GO:0021675
nerve development
5
0.01
BDNF, SLC1A3, RPL24, NGFR, EPHB1
Decreased
GO:0050890
cognition
39
0.01
OR51D1, OBP2A, OR8H3, CACNB2, TAS1R3, TIMM13, COMT, OR10G2, RIMS1, OR4F3, OR2V2, CALCA, PRKAR2B, CRYGC, BEST1, OR7G3, MCOLN3, OR8A1, IMPDH1, OR51V1, S100P, OR2AG2, OR5M10, MYO3A, FSCN2, HTT, OR8G2, OR4M2, OR52E4, PDE6G, VSX1, RGS9BP, SFRP5, TAS2R16, CRH, OR6V1, OR4N2, WDR1, CACNA1C
GO:0007600
sensory perception
33
0.04
OR51D1, OBP2A, OR8H3, CACNB2, TAS1R3, TIMM13, OR10G2, RIMS1, OR4F3, OR2V2, CALCA, CRYGC, OR7G3, BEST1, MCOLN3, OR8A1, IMPDH1, OR51V1, OR2AG2, OR5M10, MYO3A, FSCN2, OR8G2, OR4M2, OR52E4, PDE6G, VSX1, RGS9BP, SFRP5, TAS2R16, OR6V1, OR4N2, WDR1
GO:0010629
negative regulation of gene expression
25
0.01
BCLAF1, CBX2, PDX1, TNFRSF4, CALCA, MEIS2, WWP2, SND1, DDX20, NRG1, NR2F2, ZNF423, DMBX1, ZNF593, EHMT1, VHL, ARID5B, TP53, FOSB, SIRT7, MBD2, FOXP1, BRCA1, SIRT3, IRF7
GO:0006259
DNA metabolic process
23
0.03
EXO1, RBBP4, UVRAG, TP53, PAPD5, BRCA1, FOXP1, GTF2H2, GLRX2, ATRX, POLD3, CCDC111, DNASE1, FANCM, CRY2, CSNK1E, KRT7, PSIP1, TOP3A, PMS2CL, FANCA, DNAJA3, REPIN1
GO:0010817
regulation of hormone levels
11
0.01
UGT1A8, LY6E, HTT, GHRH, CHST8, CYP26B1, CRH, COMT, PDX1, CACNA1C, BCO2
GO:0010639
negative regulation of organelle organization
7
0.03
TRIOBP, ARHGAP6, TRIM54, BUB1, ADD2, BRCA1, HDAC6
GO:0009914
hormone transport
5
0.05
LY6E, HTT, GHRH, PDX1, CACNA1C
</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_39</infon><infon key="type">text</infon><offset>20412</offset></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_40</infon><infon key="type">text</infon><offset>20414</offset><text>Supplementary Table 6. Summary of mRNA-Seq alignment. AD, Alzheimer&rsquo;s disease patient; C, control normal subject.</text></passage><passage><infon key="section_type">TABLE</infon><infon key="xml"><?xml version="1.0" encoding="UTF-8"?> <table border=1><tbody><tr><td>Case</td><td>Total reads</td><td>Filtered reads</td><td>Used reads</td><td>Mapped reads</td><td>Uniquely mapped reads</td><td>Mapping rate</td><td>Depth (fold)</td></tr><tr><td>AD1</td><td>73,765,170</td><td>4,486,971</td><td>69,278,199</td><td>57,479,883</td><td>54,675,736</td><td>0.83</td><td>70.40</td></tr><tr><td>AD2</td><td>46,649,484</td><td>7,437,142</td><td>39,212,342</td><td>27,720,699</td><td>26,556,784</td><td>0.71</td><td>34.83</td></tr><tr><td>AD3</td><td>89,221,024</td><td>5,066,386</td><td>84,154,638</td><td>73,507,453</td><td>69,998,152</td><td>0.87</td><td>91.09</td></tr><tr><td>AD4</td><td>83,992,030</td><td>4,417,273</td><td>79,574,757</td><td>69,804,655</td><td>66,284,130</td><td>0.88</td><td>86.72</td></tr><tr><td>AD5</td><td>51,885,624</td><td>4,050,321</td><td>47,835,303</td><td>41,198,357</td><td>39,363,034</td><td>0.86</td><td>51.06</td></tr><tr><td>AD6</td><td>42,808,104</td><td>2,862,916</td><td>39,945,188</td><td>35,093,955</td><td>34,130,508</td><td>0.88</td><td>43.39</td></tr><tr><td>C1</td><td>86,560,836</td><td>4,096,283</td><td>82,464,553</td><td>74,746,342</td><td>72,362,323</td><td>0.91</td><td>96.21</td></tr><tr><td>C2</td><td>63,522,360</td><td>2,232,081</td><td>61,290,279</td><td>55,521,159</td><td>53,528,720</td><td>0.91</td><td>71.85</td></tr><tr><td>C3</td><td>64,903,408</td><td>4,465,589</td><td>60,437,819</td><td>53,282,648</td><td>50,998,086</td><td>0.88</td><td>68.42</td></tr><tr><td>C4</td><td>106,904,762</td><td>5,107,121</td><td>101,797,641</td><td>91,294,910</td><td>88,502,485</td><td>0.9</td><td>116.01</td></tr><tr><td>C5</td><td>88,466,194</td><td>4,063,825</td><td>84,402,369</td><td>76,614,124</td><td>74,160,506</td><td>0.91</td><td>98.78</td></tr><tr><td>C6</td><td>67,737,612</td><td>4,202,735</td><td>63,534,877</td><td>56,972,366</td><td>55,446,855</td><td>0.9</td><td>73.06</td></tr></tbody></table></infon><infon key="id">Table_41</infon><infon key="type">table</infon><offset>20528</offset><text>Case
Total reads
Filtered reads
Used reads
Mapped reads
Uniquely mapped reads
Mapping rate
Depth (fold)
AD1
73,765,170
4,486,971
69,278,199
57,479,883
54,675,736
0.83
70.40
AD2
46,649,484
7,437,142
39,212,342
27,720,699
26,556,784
0.71
34.83
AD3
89,221,024
5,066,386
84,154,638
73,507,453
69,998,152
0.87
91.09
AD4
83,992,030
4,417,273
79,574,757
69,804,655
66,284,130
0.88
86.72
AD5
51,885,624
4,050,321
47,835,303
41,198,357
39,363,034
0.86
51.06
AD6
42,808,104
2,862,916
39,945,188
35,093,955
34,130,508
0.88
43.39
C1
86,560,836
4,096,283
82,464,553
74,746,342
72,362,323
0.91
96.21
C2
63,522,360
2,232,081
61,290,279
55,521,159
53,528,720
0.91
71.85
C3
64,903,408
4,465,589
60,437,819
53,282,648
50,998,086
0.88
68.42
C4
106,904,762
5,107,121
101,797,641
91,294,910
88,502,485
0.9
116.01
C5
88,466,194
4,063,825
84,402,369
76,614,124
74,160,506
0.91
98.78
C6
67,737,612
4,202,735
63,534,877
56,972,366
55,446,855
0.9
73.06
</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_42</infon><infon key="type">text</infon><offset>21586</offset></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_43</infon><infon key="type">text</infon><offset>21588</offset><text>Supplementary Table 7. Differentially expressed genes between AD patients and normal subjects identified by EdgeR and DESeq (Please confer an attached excel file including Supplementary Table 4 and 7).</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_44</infon><infon key="type">text</infon><offset>21790</offset><text>Supplementary Table 8. GOBPs represented by the DEGs. 'Up-regulated' and 'Down-regulated' represent the GOBPs represented by the up- and down-regulated genes in AD, respectively. 'Count' means the number of the genes involved in the corresponding GOBP. Such genes are listed. FE, fold enrichment.</text></passage><passage><infon key="section_type">TABLE</infon><infon key="xml"><?xml version="1.0" encoding="UTF-8"?> <table border=1><tbody><tr><td>Change</td><td>TermID</td><td>Description</td><td>Count</td><td>FE</td><td>P-value</td><td>Genes</td></tr><tr><td>Up-regulated</td><td>GO:0022610</td><td>biological adhesion</td><td>105</td><td>1.72</td><td>0.00</td><td>ITGB3BP, DLC1, LYPD3, MMRN1, AZGP1, CD44, TGFBI, CDH26, CDH23, CLCA2, ROCK1, EFNB1, CDHR4, CDHR5, CERCAM, BCL2L11, CTNNA3, NCAM1, JUP, F5, TESK2, TGFB1I1, MFAP4, DST, TNFRSF12A, NINJ2, DSCAML1, ITGB5, NINJ1, ITGB3, ITGB1, PXN, ITGBL1, ALCAM, LAMB2, ITGAX, ITGB8, SPP1, COL18A1, BMP1, LPP, ITGA2, MCAM, ECM2, LAMA2, COL14A1, DSG2, ITGA5, PKP4, ABL1, AEBP1, PCDHA9, CLDN9, MYBPC1, FER, SRPX, WISP1, DLG5, CYR61, CNTNAP4, TRPM7, INPPL1, CPXM2, DDR1, SLC26A6, PSEN1, CNTN2, VCAN, SEMA4D, AOC3, MIA, TNC, COL3A1, CDH1, NEO1, CLDN11, CLDN15, VCAM1, CD9, ANXA9, COL6A6, FAT4, COL27A1, COL6A3, MYBPH, COL6A2, ACAN, PSTPIP1, PKD2, CD22, GP1BA, COL8A1, AMICA1, THBS2, COL8A2, HAPLN2, MAG, NFASC, HSPG2, COL4A6, CLDN23, ERBB2IP, CDH19, DSC3, MUC16</td></tr><tr><td></td><td>GO:0007155</td><td>cell adhesion</td><td>105</td><td>1.73</td><td>0.00</td><td>ITGB3BP, DLC1, LYPD3, MMRN1, AZGP1, CD44, TGFBI, CDH26, CDH23, CLCA2, ROCK1, EFNB1, CDHR4, CDHR5, CERCAM, BCL2L11, CTNNA3, NCAM1, JUP, F5, TESK2, TGFB1I1, MFAP4, DST, TNFRSF12A, NINJ2, DSCAML1, ITGB5, NINJ1, ITGB3, ITGB1, PXN, ITGBL1, ALCAM, LAMB2, ITGAX, ITGB8, SPP1, COL18A1, BMP1, LPP, ITGA2, MCAM, ECM2, LAMA2, COL14A1, DSG2, ITGA5, PKP4, ABL1, AEBP1, PCDHA9, CLDN9, MYBPC1, FER, SRPX, WISP1, DLG5, CYR61, CNTNAP4, TRPM7, INPPL1, CPXM2, DDR1, SLC26A6, PSEN1, CNTN2, VCAN, SEMA4D, AOC3, MIA, TNC, COL3A1, CDH1, NEO1, CLDN11, CLDN15, VCAM1, CD9, ANXA9, COL6A6, FAT4, COL27A1, COL6A3, MYBPH, COL6A2, ACAN, PSTPIP1, PKD2, CD22, GP1BA, COL8A1, AMICA1, THBS2, COL8A2, HAPLN2, MAG, NFASC, HSPG2, COL4A6, CLDN23, ERBB2IP, CDH19, DSC3, MUC16</td></tr><tr><td></td><td>GO:0042981</td><td>regulation of apoptotic process</td><td>100</td><td>1.43</td><td>0.00</td><td>DLC1, ITGB3BP, STAT5A, TGFB3, TNFSF15, TNFSF14, GDNF, TGFB1, PTGIS, CD44, CDKN2C, PRAME, ROCK1, ACTN4, CRYAB, RELA, PIM3, BCL2L11, NME3, ALOX15B, TIAL1, TXNDC5, MYO18A, TMX1, GSDMA, ADORA2A, ERBB3, NFKBIA, ADA, SLC11A2, PRUNE2, BMF, TRAF4, RUNX3, PLAGL2, FGD4, HIP1, COL18A1, CFLAR, MUC2, GNRH1, SPHK1, NR4A1, GAS1, ATM, P2RX7, NOTCH1, UACA, SFRP1, HDAC1, IKBKB, ABL1, NUAK2, INS-IGF2, PREX1, MITF, PAWR, BOK, AEN, POU4F1, DLG5, ALX4, IP6K2, SGK3, ARHGEF7, SMO, TNFRSF9, HIPK1, PSEN1, HIPK2, SORT1, FOXC2, NAIP, NGFR, SEMA4D, CLN8, ALOX12, MAP3K11, C6, CDH1, SFN, ZBTB16, POU3F3, BCL6, INPP5D, PCSK6, PHLDA3, TXNIP, ZFP91-CNTF, MSH6, BIRC7, IGF2, ADIPOQ, PLEKHF1, CNTF, DUSP1, NUPR1, ID3, TIAF1, IGFBP3, TP53INP1, DNM2</td></tr><tr><td></td><td>GO:0007010</td><td>cytoskeleton organization</td><td>67</td><td>1.77</td><td>0.00</td><td>DLC1, TLN1, NUAK2, CROCC, PREX1, WASF2, RHOQ, CNP, TTN, RHOU, OFD1, CTTNBP2, NDE1, DES, ANG, GSN, FMNL2, ACTN4, ROCK1, TRPM7, FOXJ1, CRYAB, ERMN, PROX1, VASP, FLNA, PLCE1, TESK2, CLN8, DST, CXCL1, SHROOM1, CAV1, HAUS5, SHROOM4, TCAP, CALD1, SIPA1, ELN, ANLN, MYO9B, RCC1, ITGB1, DAAM2, CDC42EP2, MACF1, TEKT1, KRT8, CNN2, BCL6, TEKT4, WIPF1, CNN1, TRIP10, FGD4, INF2, SUN2, RICTOR, CAPN3, SEMA6A, ERBB2IP, MYH11, MAP7, SYNM, KPTN, ABL1, ARAP1</td></tr><tr><td></td><td>GO:0007423</td><td>sensory organ development</td><td>31</td><td>1.56</td><td>0.01</td><td>TCAP, ERBB3, MITF, TGFB3, PRRX1, ZIC1, TGFB1, DFNB31, ECE1, CHD7, COL8A1, COL8A2, CDH23, MAF, CRYAB, SIX2, SIX5, DLL1, TBX1, NR4A3, GAS1, PROX1, BCL2L11, ASCL1, DDR1, SP1, SIX1, TGIF1, FOXC2, TGIF2, CLN8</td></tr><tr><td></td><td>GO:0051960</td><td>regulation of nervous system development</td><td>31</td><td>1.86</td><td>0.00</td><td>TF, ZNF488, EFNA1, TNFRSF12A, REST, TGFB1, MBP, METRN, C11ORF9, NKX6-2, S1PR5, POU3F2, CDK5RAP2, NKX2-2, SPP1, ZFP91-CNTF, MAG, ARHGEF1, PLXNB1, RELA, DLL1, ISL1, ASCL1, SMO, NOTCH1, CNTF, PSEN1, SIX1, TGIF1, TGIF2, SEMA4D, NGFR</td></tr><tr><td></td><td>GO:0009100</td><td>glycoprotein metabolic process</td><td>27</td><td>1.54</td><td>0.03</td><td>GYPC, HS3ST5, SPOCK3, GALNT6, FUT7, KEL, FUT6, TSPAN8, POMT2, B3GNT8, TRAK2, ST3GAL4, B3GNT6, ACAN, CHST14, FUT2, PCSK6, GAL3ST1, KLK6, LIPA, CHST3, ST6GALNAC2, MGAT1, MAN2A1, EGFLAM, PSEN1, LRP2</td></tr><tr><td></td><td>GO:0016055</td><td>Wnt receptor signaling pathway</td><td>21</td><td>1.82</td><td>0.01</td><td>DIXDC1, LZTS2, NKD1, RYK, MITF, TLE4, TAX1BP3, FZD5, FRZB, WISP1, MACF1, SFRP1, SFRP2, FBXW4, SFRP4, LRP6, HBP1, TGFB1I1, WNT6, AXIN1, LRP5</td></tr><tr><td></td><td>GO:0007229</td><td>integrin-mediated signaling pathway</td><td>16</td><td>2.63</td><td>0.00</td><td>PLP1, COL3A1, ITGA2, ITGB5, ITGB3, ITGB1, ITGBL1, ADAMTS7, DOCK1, GAB2, ITGAX, ERBB2IP, ITGB8, ITGA5, ADAM33, DST</td></tr><tr><td></td><td>GO:0007265</td><td>Ras protein signal transduction</td><td>16</td><td>1.75</td><td>0.04</td><td>PLD1, ARHGEF1, ROCK1, WASF2, RTKN, MYO9B, ABCA1, MAPKAPK2, TAX1BP3, RHOU, PLCE1, CDC42EP1, RASGRP3, COL1A2, RAPGEF6, RHOG</td></tr><tr><td></td><td>GO:0006643</td><td>membrane lipid metabolic process</td><td>13</td><td>1.85</td><td>0.05</td><td>ACER3, SGPL1, A4GALT, SPTLC2, SGMS2, FA2H, SPHK1, PSAPL1, ASAH2, P2RX7, ITGB8, CLN8, GAL3ST1</td></tr><tr><td></td><td>GO:0000302</td><td>response to reactive oxygen species</td><td>13</td><td>2.00</td><td>0.03</td><td>TXNIP, GNAO1, CRYAB, RELA, DUOX1, PXN, ADA, FOS, EP300, DUSP1, SERPINE1, COL1A1, FANCC</td></tr><tr><td>Down-regulated</td><td>GO:0050877</td><td>neurological system process</td><td>125</td><td>1.61</td><td>0.00</td><td>SYT1, GRIK1, GABRB3, SYT5, GRIK2, STRC, SNCA, CNGB1, VIPR1, CALB1, BDNF, IL1B, SCN2B, BAIAP3, GRIN2A, MYLK2, TIMM8B, PITPNM3, CAMK4, AKAP5, UNC13C, RBP4, DRD2, DRD5, CACNB2, RIMS1, GAD2, B3GNT1, GAD1, PLAT, GABRD, GABRA2, CPNE6, GABRA6, GABRA5, LIN7B, AFG3L2, VDAC3, NPY5R, VDAC1, PDE7B, NPY, PENK, PRKAR1B, ADRA1B, CHRNB2, CACNA1E, FABP7, CORT, SST, CRYM, ADRA1D, CACNA1B, LXN, TRPV2, TACR1, UCHL1, GABBR2, PAX2, KCNIP2, KCNIP1, CRYBB1, SLC1A4, SLC1A2, KCNQ3, SLC1A6, DLG4, SHC3, SLC1A1, EGR1, KCNMA1, STX1A, EGR3, EGR2, CNTN5, CCKBR, NRXN3, ALDH5A1, PI4KA, PRKCG, CDK5, STX1B, GNAL, GRM8, PPEF1, CHRM1, OTOF, PSEN2, RAB3A, PPFIA3, CPLX1, NDN, TH, GNG13, TIMM10, OXTR, TAC1, KIT, FKBP1B, DTNBP1, HRH1, PDE1B, SYN1, NPTX2, SYN2, PPP3CB, HTR3A, SNAP25, NEFL, APBA1, GUCA1A, DLGAP1, DLGAP2, ATP1A3, GJB6, PARK2, GRIA4, PRPH2, SLC17A7, SLC17A8, PNOC, GRIA1, CRH, HTR2C, HTR2A</td></tr><tr><td></td><td>GO:0019226</td><td>transmission of nerve impulse</td><td>84</td><td>3.73</td><td>0.00</td><td>SYT1, GRIK1, GABRB3, SYT5, GRIK2, SNCA, GABBR2, KCNIP2, VIPR1, KCNIP1, SLC1A4, SLC1A2, KCNQ3, SLC1A6, DLG4, SHC3, SLC1A1, KCNMA1, STX1A, EGR3, EGR2, SCN2B, ALDH5A1, BAIAP3, NRXN3, GRIN2A, PI4KA, MYLK2, STX1B, CDK5, CAMK4, GRM8, CHRM1, AKAP5, UNC13C, RAB3A, PPFIA3, CPLX1, DRD2, DRD5, TH, OXTR, TAC1, CACNB2, FKBP1B, RIMS1, HRH1, GAD2, SYN1, NPTX2, SYN2, PPP3CB, HTR3A, GAD1, SNAP25, APBA1, GABRD, PLAT, DLGAP1, GABRA2, DLGAP2, CPNE6, GABRA6, GABRA5, LIN7B, PARK2, GRIA4, AFG3L2, VDAC3, NPY5R, VDAC1, SLC17A7, PDE7B, PNOC, NPY, GRIA1, CRH, CACNA1E, CHRNB2, CORT, HTR2C, SST, HTR2A, CACNA1B</td></tr><tr><td></td><td>GO:0055114</td><td>oxidation-reduction process</td><td>59</td><td>1.44</td><td>0.00</td><td>LDHA, KCNAB2, SNCA, NDUFAB1, PRDX2, HSD11B1L, COX5A, UQCRFS1, GLDC, NDUFS5, MSRA, NDUFS4, ALOX12B, SRD5A1, ASPH, SARDH, PCYOX1L, ALDH5A1, MICAL2, F8, NDUFC2, CYP4X1, DHRS2, UQCRH, FDX1L, STEAP2, MECR, MDH2, MDH1, NDUFB3, ME1, ME3, NDUFB6, TH, KMO, CYP26B1, IDH2, HSD17B6, DMGDH, SDR16C5, BDH1, TYW1B, CYP2B7P1, HSD17B8, GLRX, NDUFA4, NDUFA5, NOX5, NDUFA8, CYP46A1, CYP2C8, NDUFA7, DHRS11, HGD, BLVRA, CYP4A11, VAT1L, DIO2, MPO</td></tr><tr><td></td><td>GO:0030182</td><td>neuron differentiation</td><td>57</td><td>2.02</td><td>0.00</td><td>GPRIN1, TUBB2B, TUBB2A, UCHL1, KCNIP2, PAX2, LUZP6, CDC42, WNT1, BDNF, ATXN10, PAX7, ROBO2, SPON2, TUBB3, KCNMA1, EGR2, EFNB3, STMN2, NRXN3, PTPRR, CDK5, SLIT1, NUMBL, NDEL1, RND1, GAP43, KALRN, RAB3A, CDK5R1, CCK, LPPR4, NDN, RTN4RL1, DRD2, TH, NNAT, HPRT1, LINGO1, TUBB, PTK2B, MTPN, B3GNT1, LHX6, RTN4RL2, LAMB1, NEFL, SNAP25, DCLK1, IL6, GNAO1, BHLHE22, NTNG1, AFG3L2, DLX1, DLX5, MAP2, CHRNB2</td></tr><tr><td></td><td>GO:0051726</td><td>regulation of cell cycle</td><td>33</td><td>1.55</td><td>0.01</td><td>CDK5R1, CDK5R2, NEK2, EDN1, MOV10L1, PIN1, ADCYAP1, CDC42, DIRAS3, OVOL2, NPM2, CDKN2D, BUB1, CAMK2D, IL1B, RANBP1, ZWILCH, CDC7, CDK1, FAM5B, CENPF, MYLK2, INHA, CDKN3, CDK5, PKIA, PLK4, MAD2L1, CCND2, ZWINT, BRE, MYO16, GADD45A</td></tr><tr><td></td><td>GO:0007611</td><td>learning or memory</td><td>31</td><td>4.34</td><td>0.00</td><td>DRD2, DRD5, TACR1, TH, OXTR, TAC1, KIT, CALB1, BDNF, PDE1B, DLG4, IL1B, SHC3, SNAP25, EGR1, EGR2, GABRA5, ATP1A3, GRIN2A, PRKCG, PARK2, CDK5, VDAC3, VDAC1, GRIA1, PRKAR1B, PSEN2, ADRA1B, CRH, CHRNB2, HTR2A</td></tr><tr><td></td><td>GO:0042493</td><td>response to drug</td><td>26</td><td>1.87</td><td>0.00</td><td>YWHAZ, STAR, DRD2, SNCA, HMGCS1, OXTR, TIMP4, UQCRFS1, PCSK1, SLC1A2, BDNF, PTK2B, IL1B, SRD5A1, RAB6A, GNAO1, ATP1A3, GRIN2A, CENPF, STAT1, NME1, FABP3, SST, HTR2C, HTR2A, SLC46A2</td></tr><tr><td></td><td>GO:0006836</td><td>neurotransmitter transport</td><td>22</td><td>4.12</td><td>0.00</td><td>SYT1, PPFIA3, RAB3A, CPLX2, ICA1, GABRA2, STX1A, CPLX1, BAIAP3, NRXN3, LIN7B, PARK2, SLC6A17, STX1B, RIMS1, SLC17A7, SLC32A1, SLC17A8, SYN1, SYN2, SV2B, SNAP25</td></tr><tr><td></td><td>GO:0009416</td><td>response to light stimulus</td><td>17</td><td>1.92</td><td>0.02</td><td>GUCA1A, RBP4, DRD2, DRD5, GRIN2A, ATP1A3, CNGB1, KIT, CDK5, GTF2H2, SLC1A2, RPAIN, PDE1B, CDKN2D, ADRA1B, CHRNB2, TUBB3</td></tr><tr><td></td><td>GO:0048511</td><td>rhythmic process</td><td>15</td><td>1.82</td><td>0.04</td><td>KCNMA1, EGR3, EGR2, DRD2, GRIN2A, OXTR, TIMP4, INHA, VGF, NPY5R, CCND2, CRH, CHRNB2, ATOH7, FSHB</td></tr><tr><td></td><td>GO:0019933</td><td>cAMP-mediated signaling</td><td>15</td><td>2.46</td><td>0.00</td><td>MCHR1, PTGER3, DRD2, DRD5, FPR1, P2RY12, PTHLH, CRHR1, GNAL, NDUFS4, ADRA1B, MC4R, RAPGEF4, CORT, ADRA1D</td></tr><tr><td></td><td>GO:0048015</td><td>phosphatidylinositol-mediated signaling</td><td>14</td><td>2.47</td><td>0.00</td><td>PTGER3, CCKBR, DRD2, DRD5, TACR1, EDN1, PI4KA, GNG13, HRH1, NPY, CHRM1, ZWINT, HTR2C, HTR2A</td></tr><tr><td></td><td>GO:0007200</td><td>phospholipase C-activating G-protein coupled receptor signaling pathway</td><td>11</td><td>3.29</td><td>0.00</td><td>HRH1, PTGER3, CCKBR, DRD2, TACR1, DRD5, CHRM1, EDN1, GNG13, HTR2C, HTR2A</td></tr><tr><td></td><td>GO:0007215</td><td>glutamate receptor signaling pathway</td><td>8</td><td>4.98</td><td>0.00</td><td>CDK5R1, GRIK1, SSTR1, GRIK2, ATP1A3, GRIN2A, GRIA3, GRIA4</td></tr><tr><td></td><td>GO:0042417</td><td>dopamine metabolic process</td><td>7</td><td>5.44</td><td>0.00</td><td>SNCB, DRD2, TH, SNCA, GRIN2A, PARK2, HPRT1</td></tr><tr><td></td><td>GO:0007212</td><td>dopamine receptor signaling pathway</td><td>6</td><td>5.18</td><td>0.00</td><td>GNAL, CALY, GNAO1, DRD2, DRD5, HMP19</td></tr></tbody></table></infon><infon key="id">Table_45</infon><infon key="type">table</infon><offset>22087</offset><text>Change
TermID
Description
Count
FE
P-value
Genes
Up-regulated
GO:0022610
biological adhesion
105
1.72
0.00
ITGB3BP, DLC1, LYPD3, MMRN1, AZGP1, CD44, TGFBI, CDH26, CDH23, CLCA2, ROCK1, EFNB1, CDHR4, CDHR5, CERCAM, BCL2L11, CTNNA3, NCAM1, JUP, F5, TESK2, TGFB1I1, MFAP4, DST, TNFRSF12A, NINJ2, DSCAML1, ITGB5, NINJ1, ITGB3, ITGB1, PXN, ITGBL1, ALCAM, LAMB2, ITGAX, ITGB8, SPP1, COL18A1, BMP1, LPP, ITGA2, MCAM, ECM2, LAMA2, COL14A1, DSG2, ITGA5, PKP4, ABL1, AEBP1, PCDHA9, CLDN9, MYBPC1, FER, SRPX, WISP1, DLG5, CYR61, CNTNAP4, TRPM7, INPPL1, CPXM2, DDR1, SLC26A6, PSEN1, CNTN2, VCAN, SEMA4D, AOC3, MIA, TNC, COL3A1, CDH1, NEO1, CLDN11, CLDN15, VCAM1, CD9, ANXA9, COL6A6, FAT4, COL27A1, COL6A3, MYBPH, COL6A2, ACAN, PSTPIP1, PKD2, CD22, GP1BA, COL8A1, AMICA1, THBS2, COL8A2, HAPLN2, MAG, NFASC, HSPG2, COL4A6, CLDN23, ERBB2IP, CDH19, DSC3, MUC16
GO:0007155
cell adhesion
105
1.73
0.00
ITGB3BP, DLC1, LYPD3, MMRN1, AZGP1, CD44, TGFBI, CDH26, CDH23, CLCA2, ROCK1, EFNB1, CDHR4, CDHR5, CERCAM, BCL2L11, CTNNA3, NCAM1, JUP, F5, TESK2, TGFB1I1, MFAP4, DST, TNFRSF12A, NINJ2, DSCAML1, ITGB5, NINJ1, ITGB3, ITGB1, PXN, ITGBL1, ALCAM, LAMB2, ITGAX, ITGB8, SPP1, COL18A1, BMP1, LPP, ITGA2, MCAM, ECM2, LAMA2, COL14A1, DSG2, ITGA5, PKP4, ABL1, AEBP1, PCDHA9, CLDN9, MYBPC1, FER, SRPX, WISP1, DLG5, CYR61, CNTNAP4, TRPM7, INPPL1, CPXM2, DDR1, SLC26A6, PSEN1, CNTN2, VCAN, SEMA4D, AOC3, MIA, TNC, COL3A1, CDH1, NEO1, CLDN11, CLDN15, VCAM1, CD9, ANXA9, COL6A6, FAT4, COL27A1, COL6A3, MYBPH, COL6A2, ACAN, PSTPIP1, PKD2, CD22, GP1BA, COL8A1, AMICA1, THBS2, COL8A2, HAPLN2, MAG, NFASC, HSPG2, COL4A6, CLDN23, ERBB2IP, CDH19, DSC3, MUC16
GO:0042981
regulation of apoptotic process
100
1.43
0.00
DLC1, ITGB3BP, STAT5A, TGFB3, TNFSF15, TNFSF14, GDNF, TGFB1, PTGIS, CD44, CDKN2C, PRAME, ROCK1, ACTN4, CRYAB, RELA, PIM3, BCL2L11, NME3, ALOX15B, TIAL1, TXNDC5, MYO18A, TMX1, GSDMA, ADORA2A, ERBB3, NFKBIA, ADA, SLC11A2, PRUNE2, BMF, TRAF4, RUNX3, PLAGL2, FGD4, HIP1, COL18A1, CFLAR, MUC2, GNRH1, SPHK1, NR4A1, GAS1, ATM, P2RX7, NOTCH1, UACA, SFRP1, HDAC1, IKBKB, ABL1, NUAK2, INS-IGF2, PREX1, MITF, PAWR, BOK, AEN, POU4F1, DLG5, ALX4, IP6K2, SGK3, ARHGEF7, SMO, TNFRSF9, HIPK1, PSEN1, HIPK2, SORT1, FOXC2, NAIP, NGFR, SEMA4D, CLN8, ALOX12, MAP3K11, C6, CDH1, SFN, ZBTB16, POU3F3, BCL6, INPP5D, PCSK6, PHLDA3, TXNIP, ZFP91-CNTF, MSH6, BIRC7, IGF2, ADIPOQ, PLEKHF1, CNTF, DUSP1, NUPR1, ID3, TIAF1, IGFBP3, TP53INP1, DNM2
GO:0007010
cytoskeleton organization
67
1.77
0.00
DLC1, TLN1, NUAK2, CROCC, PREX1, WASF2, RHOQ, CNP, TTN, RHOU, OFD1, CTTNBP2, NDE1, DES, ANG, GSN, FMNL2, ACTN4, ROCK1, TRPM7, FOXJ1, CRYAB, ERMN, PROX1, VASP, FLNA, PLCE1, TESK2, CLN8, DST, CXCL1, SHROOM1, CAV1, HAUS5, SHROOM4, TCAP, CALD1, SIPA1, ELN, ANLN, MYO9B, RCC1, ITGB1, DAAM2, CDC42EP2, MACF1, TEKT1, KRT8, CNN2, BCL6, TEKT4, WIPF1, CNN1, TRIP10, FGD4, INF2, SUN2, RICTOR, CAPN3, SEMA6A, ERBB2IP, MYH11, MAP7, SYNM, KPTN, ABL1, ARAP1
GO:0007423
sensory organ development
31
1.56
0.01
TCAP, ERBB3, MITF, TGFB3, PRRX1, ZIC1, TGFB1, DFNB31, ECE1, CHD7, COL8A1, COL8A2, CDH23, MAF, CRYAB, SIX2, SIX5, DLL1, TBX1, NR4A3, GAS1, PROX1, BCL2L11, ASCL1, DDR1, SP1, SIX1, TGIF1, FOXC2, TGIF2, CLN8
GO:0051960
regulation of nervous system development
31
1.86
0.00
TF, ZNF488, EFNA1, TNFRSF12A, REST, TGFB1, MBP, METRN, C11ORF9, NKX6-2, S1PR5, POU3F2, CDK5RAP2, NKX2-2, SPP1, ZFP91-CNTF, MAG, ARHGEF1, PLXNB1, RELA, DLL1, ISL1, ASCL1, SMO, NOTCH1, CNTF, PSEN1, SIX1, TGIF1, TGIF2, SEMA4D, NGFR
GO:0009100
glycoprotein metabolic process
27
1.54
0.03
GYPC, HS3ST5, SPOCK3, GALNT6, FUT7, KEL, FUT6, TSPAN8, POMT2, B3GNT8, TRAK2, ST3GAL4, B3GNT6, ACAN, CHST14, FUT2, PCSK6, GAL3ST1, KLK6, LIPA, CHST3, ST6GALNAC2, MGAT1, MAN2A1, EGFLAM, PSEN1, LRP2
GO:0016055
Wnt receptor signaling pathway
21
1.82
0.01
DIXDC1, LZTS2, NKD1, RYK, MITF, TLE4, TAX1BP3, FZD5, FRZB, WISP1, MACF1, SFRP1, SFRP2, FBXW4, SFRP4, LRP6, HBP1, TGFB1I1, WNT6, AXIN1, LRP5
GO:0007229
integrin-mediated signaling pathway
16
2.63
0.00
PLP1, COL3A1, ITGA2, ITGB5, ITGB3, ITGB1, ITGBL1, ADAMTS7, DOCK1, GAB2, ITGAX, ERBB2IP, ITGB8, ITGA5, ADAM33, DST
GO:0007265
Ras protein signal transduction
16
1.75
0.04
PLD1, ARHGEF1, ROCK1, WASF2, RTKN, MYO9B, ABCA1, MAPKAPK2, TAX1BP3, RHOU, PLCE1, CDC42EP1, RASGRP3, COL1A2, RAPGEF6, RHOG
GO:0006643
membrane lipid metabolic process
13
1.85
0.05
ACER3, SGPL1, A4GALT, SPTLC2, SGMS2, FA2H, SPHK1, PSAPL1, ASAH2, P2RX7, ITGB8, CLN8, GAL3ST1
GO:0000302
response to reactive oxygen species
13
2.00
0.03
TXNIP, GNAO1, CRYAB, RELA, DUOX1, PXN, ADA, FOS, EP300, DUSP1, SERPINE1, COL1A1, FANCC
Down-regulated
GO:0050877
neurological system process
125
1.61
0.00
SYT1, GRIK1, GABRB3, SYT5, GRIK2, STRC, SNCA, CNGB1, VIPR1, CALB1, BDNF, IL1B, SCN2B, BAIAP3, GRIN2A, MYLK2, TIMM8B, PITPNM3, CAMK4, AKAP5, UNC13C, RBP4, DRD2, DRD5, CACNB2, RIMS1, GAD2, B3GNT1, GAD1, PLAT, GABRD, GABRA2, CPNE6, GABRA6, GABRA5, LIN7B, AFG3L2, VDAC3, NPY5R, VDAC1, PDE7B, NPY, PENK, PRKAR1B, ADRA1B, CHRNB2, CACNA1E, FABP7, CORT, SST, CRYM, ADRA1D, CACNA1B, LXN, TRPV2, TACR1, UCHL1, GABBR2, PAX2, KCNIP2, KCNIP1, CRYBB1, SLC1A4, SLC1A2, KCNQ3, SLC1A6, DLG4, SHC3, SLC1A1, EGR1, KCNMA1, STX1A, EGR3, EGR2, CNTN5, CCKBR, NRXN3, ALDH5A1, PI4KA, PRKCG, CDK5, STX1B, GNAL, GRM8, PPEF1, CHRM1, OTOF, PSEN2, RAB3A, PPFIA3, CPLX1, NDN, TH, GNG13, TIMM10, OXTR, TAC1, KIT, FKBP1B, DTNBP1, HRH1, PDE1B, SYN1, NPTX2, SYN2, PPP3CB, HTR3A, SNAP25, NEFL, APBA1, GUCA1A, DLGAP1, DLGAP2, ATP1A3, GJB6, PARK2, GRIA4, PRPH2, SLC17A7, SLC17A8, PNOC, GRIA1, CRH, HTR2C, HTR2A
GO:0019226
transmission of nerve impulse
84
3.73
0.00
SYT1, GRIK1, GABRB3, SYT5, GRIK2, SNCA, GABBR2, KCNIP2, VIPR1, KCNIP1, SLC1A4, SLC1A2, KCNQ3, SLC1A6, DLG4, SHC3, SLC1A1, KCNMA1, STX1A, EGR3, EGR2, SCN2B, ALDH5A1, BAIAP3, NRXN3, GRIN2A, PI4KA, MYLK2, STX1B, CDK5, CAMK4, GRM8, CHRM1, AKAP5, UNC13C, RAB3A, PPFIA3, CPLX1, DRD2, DRD5, TH, OXTR, TAC1, CACNB2, FKBP1B, RIMS1, HRH1, GAD2, SYN1, NPTX2, SYN2, PPP3CB, HTR3A, GAD1, SNAP25, APBA1, GABRD, PLAT, DLGAP1, GABRA2, DLGAP2, CPNE6, GABRA6, GABRA5, LIN7B, PARK2, GRIA4, AFG3L2, VDAC3, NPY5R, VDAC1, SLC17A7, PDE7B, PNOC, NPY, GRIA1, CRH, CACNA1E, CHRNB2, CORT, HTR2C, SST, HTR2A, CACNA1B
GO:0055114
oxidation-reduction process
59
1.44
0.00
LDHA, KCNAB2, SNCA, NDUFAB1, PRDX2, HSD11B1L, COX5A, UQCRFS1, GLDC, NDUFS5, MSRA, NDUFS4, ALOX12B, SRD5A1, ASPH, SARDH, PCYOX1L, ALDH5A1, MICAL2, F8, NDUFC2, CYP4X1, DHRS2, UQCRH, FDX1L, STEAP2, MECR, MDH2, MDH1, NDUFB3, ME1, ME3, NDUFB6, TH, KMO, CYP26B1, IDH2, HSD17B6, DMGDH, SDR16C5, BDH1, TYW1B, CYP2B7P1, HSD17B8, GLRX, NDUFA4, NDUFA5, NOX5, NDUFA8, CYP46A1, CYP2C8, NDUFA7, DHRS11, HGD, BLVRA, CYP4A11, VAT1L, DIO2, MPO
GO:0030182
neuron differentiation
57
2.02
0.00
GPRIN1, TUBB2B, TUBB2A, UCHL1, KCNIP2, PAX2, LUZP6, CDC42, WNT1, BDNF, ATXN10, PAX7, ROBO2, SPON2, TUBB3, KCNMA1, EGR2, EFNB3, STMN2, NRXN3, PTPRR, CDK5, SLIT1, NUMBL, NDEL1, RND1, GAP43, KALRN, RAB3A, CDK5R1, CCK, LPPR4, NDN, RTN4RL1, DRD2, TH, NNAT, HPRT1, LINGO1, TUBB, PTK2B, MTPN, B3GNT1, LHX6, RTN4RL2, LAMB1, NEFL, SNAP25, DCLK1, IL6, GNAO1, BHLHE22, NTNG1, AFG3L2, DLX1, DLX5, MAP2, CHRNB2
GO:0051726
regulation of cell cycle
33
1.55
0.01
CDK5R1, CDK5R2, NEK2, EDN1, MOV10L1, PIN1, ADCYAP1, CDC42, DIRAS3, OVOL2, NPM2, CDKN2D, BUB1, CAMK2D, IL1B, RANBP1, ZWILCH, CDC7, CDK1, FAM5B, CENPF, MYLK2, INHA, CDKN3, CDK5, PKIA, PLK4, MAD2L1, CCND2, ZWINT, BRE, MYO16, GADD45A
GO:0007611
learning or memory
31
4.34
0.00
DRD2, DRD5, TACR1, TH, OXTR, TAC1, KIT, CALB1, BDNF, PDE1B, DLG4, IL1B, SHC3, SNAP25, EGR1, EGR2, GABRA5, ATP1A3, GRIN2A, PRKCG, PARK2, CDK5, VDAC3, VDAC1, GRIA1, PRKAR1B, PSEN2, ADRA1B, CRH, CHRNB2, HTR2A
GO:0042493
response to drug
26
1.87
0.00
YWHAZ, STAR, DRD2, SNCA, HMGCS1, OXTR, TIMP4, UQCRFS1, PCSK1, SLC1A2, BDNF, PTK2B, IL1B, SRD5A1, RAB6A, GNAO1, ATP1A3, GRIN2A, CENPF, STAT1, NME1, FABP3, SST, HTR2C, HTR2A, SLC46A2
GO:0006836
neurotransmitter transport
22
4.12
0.00
SYT1, PPFIA3, RAB3A, CPLX2, ICA1, GABRA2, STX1A, CPLX1, BAIAP3, NRXN3, LIN7B, PARK2, SLC6A17, STX1B, RIMS1, SLC17A7, SLC32A1, SLC17A8, SYN1, SYN2, SV2B, SNAP25
GO:0009416
response to light stimulus
17
1.92
0.02
GUCA1A, RBP4, DRD2, DRD5, GRIN2A, ATP1A3, CNGB1, KIT, CDK5, GTF2H2, SLC1A2, RPAIN, PDE1B, CDKN2D, ADRA1B, CHRNB2, TUBB3
GO:0048511
rhythmic process
15
1.82
0.04
KCNMA1, EGR3, EGR2, DRD2, GRIN2A, OXTR, TIMP4, INHA, VGF, NPY5R, CCND2, CRH, CHRNB2, ATOH7, FSHB
GO:0019933
cAMP-mediated signaling
15
2.46
0.00
MCHR1, PTGER3, DRD2, DRD5, FPR1, P2RY12, PTHLH, CRHR1, GNAL, NDUFS4, ADRA1B, MC4R, RAPGEF4, CORT, ADRA1D
GO:0048015
phosphatidylinositol-mediated signaling
14
2.47
0.00
PTGER3, CCKBR, DRD2, DRD5, TACR1, EDN1, PI4KA, GNG13, HRH1, NPY, CHRM1, ZWINT, HTR2C, HTR2A
GO:0007200
phospholipase C-activating G-protein coupled receptor signaling pathway
11
3.29
0.00
HRH1, PTGER3, CCKBR, DRD2, TACR1, DRD5, CHRM1, EDN1, GNG13, HTR2C, HTR2A
GO:0007215
glutamate receptor signaling pathway
8
4.98
0.00
CDK5R1, GRIK1, SSTR1, GRIK2, ATP1A3, GRIN2A, GRIA3, GRIA4
GO:0042417
dopamine metabolic process
7
5.44
0.00
SNCB, DRD2, TH, SNCA, GRIN2A, PARK2, HPRT1
GO:0007212
dopamine receptor signaling pathway
6
5.18
0.00
GNAL, CALY, GNAO1, DRD2, DRD5, HMP19
</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_46</infon><infon key="type">text</infon><offset>31470</offset></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_47</infon><infon key="type">text</infon><offset>31472</offset><text>Supplementary Table 9. Quantitative PCR (q-PCR) primer sequences for determining the relative expression of H3K9me3-landscaped epigenome.</text></passage><passage><infon key="section_type">TABLE</infon><infon key="xml"><?xml version="1.0" encoding="UTF-8"?> <table border=1><tbody><tr><td>Gene</td><td>Sequence</td></tr><tr><td>BDNF</td><td>F: GCTGCAAACATGTCCATGAG</td></tr><tr><td></td><td>R: GTAACCCATGGGATTGCACT</td></tr><tr><td>GABBR1</td><td>F: AAGAGTGTGTCCACTGAGAA</td></tr><tr><td></td><td>R: AGGAGGAGAAAACTATGGCA</td></tr><tr><td>GABRA2</td><td>F: TCGAATTCAGGATGATGGGA</td></tr><tr><td></td><td>R: AGGAGCAACCTGTACTGAAT</td></tr><tr><td>GPRASP1</td><td>F: TCTGTTAAGACACCCTGGTT</td></tr><tr><td></td><td>R: ACTCCAAATGGTCTTCATGC</td></tr><tr><td>HIST2H2BE</td><td>F: AAAAAGGGCTCCAAGAAAGC</td></tr><tr><td></td><td>R: TCGAAGATGTCGTTGACGAA</td></tr><tr><td>ID3</td><td>F: ACGACATGAACCACTGCTAC</td></tr><tr><td></td><td>R: CGTTGGAGATGACAAGTTCC</td></tr><tr><td>KIF1C</td><td>F: ACTCGGAGAAGGTCAGTAAG</td></tr><tr><td></td><td>R: AGAGTCCCTGTAGGGGATAA</td></tr><tr><td>NCALD</td><td>F: CAGAGCATGAGATCCAGGAA</td></tr><tr><td></td><td>R: TTCCCCCTCGAAGTTACACT</td></tr><tr><td>SEPT4</td><td>F: GACAAGGAGTATGTGGGCTT</td></tr><tr><td></td><td>R: CCACTGCATGCTTAGTGATC</td></tr><tr><td>SYT12</td><td>F: TTGGCATCGATGAGGATGAG</td></tr><tr><td></td><td>R: TGAGGTTCTTGGCCTTAACC</td></tr></tbody></table></infon><infon key="id">Table_48</infon><infon key="type">table</infon><offset>31610</offset><text>Gene
Sequence
BDNF
F: GCTGCAAACATGTCCATGAG
R: GTAACCCATGGGATTGCACT
GABBR1
F: AAGAGTGTGTCCACTGAGAA
R: AGGAGGAGAAAACTATGGCA
GABRA2
F: TCGAATTCAGGATGATGGGA
R: AGGAGCAACCTGTACTGAAT
GPRASP1
F: TCTGTTAAGACACCCTGGTT
R: ACTCCAAATGGTCTTCATGC
HIST2H2BE
F: AAAAAGGGCTCCAAGAAAGC
R: TCGAAGATGTCGTTGACGAA
ID3
F: ACGACATGAACCACTGCTAC
R: CGTTGGAGATGACAAGTTCC
KIF1C
F: ACTCGGAGAAGGTCAGTAAG
R: AGAGTCCCTGTAGGGGATAA
NCALD
F: CAGAGCATGAGATCCAGGAA
R: TTCCCCCTCGAAGTTACACT
SEPT4
F: GACAAGGAGTATGTGGGCTT
R: CCACTGCATGCTTAGTGATC
SYT12
F: TTGGCATCGATGAGGATGAG
R: TGAGGTTCTTGGCCTTAACC
</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_49</infon><infon key="type">text</infon><offset>32264</offset><text>Supplementary Figure 1. The occupancy of H3K9me3 is altered in AD. (A) The change of H3K9me3 enrichment on chromosomes of brain samples from AD patients (AD) and normal control subjects (Control). (B) The occupancy of H3K9me3 on the centromere of chromosome 5. IGV plots were derived from each AD patient (A2-A5) and normal control subject (C2-C6).</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_50</infon><infon key="type">text</infon><offset>32613</offset><text>Supplementary Figure 2. Expression stratified association analysis. H3K9me3 profiles of the two sets of genes with high (A) and low (B) mRNA expression levels, respectively. In the analysis for each set of genes, three kinds of gene exclusion were used: 1) no exclusion was done (no exclusion) and 2-3) genes shorter than 3K (3K exclusion) and 5K (5K exclusion) were excluded.</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_51</infon><infon key="type">text</infon><offset>32990</offset><text>Supplementary Figure 3. An inverse correlation between the enrichment of H3K9me3 (black line) and the expression level of mRNA (blue line) is found in the cortex of AD patients.</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_52</infon><infon key="type">text</infon><offset>33168</offset><text>Supplementary Figure 4. Quantitative real-time PCR (qPCR) verifies that H3K9me3-landscaped transcriptomes are altered in AD. (A) SEPT4 and KIF1c were up regulated in AD patients (N=20) compared to normal subjects (N=20). The occupancy of H3K9me3 in the promoter regions of these genes was lower in AD. Significantly different at **, p &lt;0.001. (B) ID3 and HIST2H2BE were up regulated in AD patients (n=20) compared to normal subjects (n=20). The occupancy of H3K9me3 in the promoter regions of these genes was higher in AD. Significantly different at **, p&lt;0.001. (C) Eight groups of DMGs and DEGs were analyzed and presented in the heat map.</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_53</infon><infon key="type">text</infon><offset>33811</offset><text>Supplementary Figure 5. H3K9me3-landscaped epigenome signatures are differentially modulated in a cell-type-specific manner. (A) Venn diagram summarizing the association between differentially H3K9me3-occupied genes (DMGs) and differentially expressed genes (DEGs). (B) Top 10 GO enrichment analysis of common genes between DMGs and DEGs. Neuron part pathway was shown to be highly enriched in AD. (C) Heatmap depicting the hypomethylated (low level of H3K9me3) and up-regulated genes in neuron part pathway. (D) Heatmap representing the hypermethylated (high level of H3K9me3) and down-regulated genes in neuron part pathway</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_54</infon><infon key="type">text</infon><offset>34437</offset><text>Supplementary Figure 6. Cell-type-specific genes sorted by H3K9me3 occupancy (DMG). (A) Astrocytes, (B) Oligodendrocytes, (C) Microglia, and (D) Endothelial cells. The cell-type-specific genes were marked in the Supplementary Table 4 and 7.</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_55</infon><infon key="type">text</infon><offset>34678</offset><text>Supplementary Figure 7. Cell-type-specific genes sorted by mRNA expression level (DEG). (A) Astrocytes, (B) Oligodendrocytes, (C) Microglia, and (D) Endothelial cells. The cell-type-specific genes were marked in the Supplementary Table 4 and 7.</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_56</infon><infon key="type">text</infon><offset>34923</offset><text>Supplementary Figure 8. H3K9me3-landscaped epigenome signatures are differentially modulated in a cell-type (astrocyte, oligodendrocyte, and microglia)-specific manner. (A) Comparison of the number of differentially methylated genes (DMGs) and differentially expressed genes (DEGs) (B) Heatmaps depicting the hypomethylated (left) and up-regulated genes (right) of cell-type-specific genes (astrocytes and oligodendrocytes). (C) Heatmap representing the hypermethylated (left) and down-regulated genes (right) in microglia.</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_57</infon><infon key="type">text</infon><offset>35448</offset><text>Supplementary Figure 9. H3K9me3-positive heterochromatin structure is altered in AD transgenic mouse models. (A and B) Confocal microscopy image and densitometry analysis showed that the intensity of H3K9me3-positive heterochromatin was significantly increased in the cortex of APP/PS1 mutant mice (n=3) compared to WT mice (n=3). (C and D) H3K9me3-postive chromatin condensation was increased in the cortex of 5xFAD mice (n=3) compared to WT mice (n=3). **, Significantly different from WT at p &lt; 0.01.</text></passage><passage><infon key="section_type">TEXT</infon><infon key="id">Text_58</infon><infon key="type">text</infon><offset>35953</offset><text>Supplementary Figure 10. The whole Western blot image of H3K9me3 and histone H3 those are presented in the main Figure 1.</text></passage></document></collection> |