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pmid:33116763

Identifying the Mechanisms and Molecular Targets of Yizhiqingxin Formula on Alzheimer's Disease: Coupling Network Pharmacology with GEO Database.

Tingting Zhang · Linlin Pan · Yu Cao · Nanyang Liu · Wei Wei · Hao Li

Pharmacogenomics and personalized medicine · 2020 doi:10.2147/PGPM.S269726

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Experiment

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Data

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pmid:33116763
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2026-11-01T15:41:14Z
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2026-11-01T22:02:25Z
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title
Identifying the Mechanisms and Molecular Targets of Yizhiqingxin Formula on Alzheimer's Disease: Coupling Network Pharmacology with GEO Database.
doi
10.2147/PGPM.S269726
pmid
33116763
authors array · 6 items
[0]
Tingting Zhang
[1]
Linlin Pan
[2]
Yu Cao
[3]
Nanyang Liu
[4]
Wei Wei
[5]
Hao Li
journal
Pharmacogenomics and personalized medicine
year
2020
abstract
BACKGROUND: Yizhiqingxin formula (YZQX) is a promising formula for the treatment of Alzheimer's disease (AD) with significant clinical effects. Here, we coupled a network pharmacology approach with the Gene Expression Omnibus (GEO) database to illustrate comprehensive mechanisms and screen for molecular targets of YZQX for AD treatment. METHODS: First, active ingredients of YZQX were screened for the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database with the absorption, distribution, metabolism, and excretion (ADME) parameters. Subsequently, putative targets of active ingredients were predicted using the DrugBank database. AD-related targets were retrieved by analyzing published microarray data (accession number GSE5281). Protein-protein interaction (PPI) networks of YZQX putative targets and AD-related targets were constructed visually and merged to identify candidate targets for YZQX against AD using Cytoscape 3.7.2 software. We performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to further clarify the biological functions of the candidate targets. The gene-pathway network was established to filter for key target genes. RESULTS: Forty-three active ingredients were identified, and 193 putative target genes were predicted. Seven hundred and ten targets related to AD were screened with |log2 FC| > 1 and P < 0.05. Based on the PPI network, 110 target genes of YZQX against AD were identified. Moreover, 32 related pathways including the PI3K-Akt signaling pathway, MAPK signaling pathway, ubiquitin-mediated proteolysis, apoptosis and the NF-kappa B signaling pathway were significantly enriched. In the gene-pathway network, MAPK1, AKT1, TP53, MDM2, EGFR, RELA, SRC, GRB2, CUL1, and MYC targets are putative core genes for YZQX in AD treatment. CONCLUSION: YZQX against AD may exert its neuroprotective effect via the PI3K-Akt signaling pathway, MAPK signaling pathway, and ubiquitin-mediated proteolysis. YZQX may be a promising drug that can be used in the treatment of AD.
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Expression profiling data from GSE5281 were downloaded from the GEO database (http://www.ncbi.nlm.nih.gov/geo/) based on the microarray platform GPL570 (Affymetrix Human Gene Expression Array), which contained 74 samples from healthy individuals and 87 AD samples.
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Expression profiling data from GSE5281 were downloaded from the GEO database (http://www.ncbi.nlm.nih.gov/geo/) based on the microarray platform GPL570 (Affymetrix Human Gene Expression Array), which contained 74 samples from healthy individuals and 87 AD samples.
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Alzheimer's disease and the normal aged brain (steph-affy-human-433773)
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The Final Selected Ingredients in YZQX for Analysis
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Screening of Bioactive Ingredients and Putative Targets from YZQX
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Table 1
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The Final Selected Ingredients in YZQX for Analysis
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The Key Parameter Values of 110 Core Targets
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PPI Network Construction, Merging, and Analysis
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Table 2
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The Key Parameter Values of 110 Core Targets
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[3]
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[1]
12,720.53
[2]
0.607809
[3]
635
[4]
0.097986
[5]
47.78167
[6]
159.2176
[12] array · 7 items
[0]
CDK2
[1]
13,079.84
[2]
0.59977
[3]
622
[4]
0.090112
[5]
45.10315
[6]
142.7661
[13] array · 7 items
[0]
UBC
[1]
12,601.12
[2]
0.585626
[3]
614
[4]
0.071026
[5]
43.33876
[6]
131.519
[14] array · 7 items
[0]
COPS5
[1]
8276.179
[2]
0.592951
[3]
613
[4]
0.094499
[5]
54.41768
[6]
148.6378
[15] array · 7 items
[0]
CUL1
[1]
8951.929
[2]
0.593288
[3]
564
[4]
0.094188
[5]
55.54103
[6]
152.807
[16] array · 7 items
[0]
CUL7
[1]
9990.143
[2]
0.599425
[3]
552
[4]
0.089742
[5]
43.08069
[6]
136.2477
[17] array · 7 items
[0]
RNF2
[1]
9862.539
[2]
0.584641
[3]
525
[4]
0.074703
[5]
37.84158
[6]
110.2017
[18] array · 7 items
[0]
CAND1
[1]
6260.668
[2]
0.582682
[3]
508
[4]
0.090651
[5]
58.54333
[6]
146.2511
[19] array · 7 items
[0]
MYC
[1]
5971.691
[2]
0.55985
[3]
503
[4]
0.048495
[5]
29.34222
[6]
67.73357
[20] array · 7 items
[0]
SIRT7
[1]
6146.117
[2]
0.569013
[3]
496
[4]
0.067372
[5]
34.51938
[6]
80.48613
[21] array · 7 items
[0]
OBSL1
[1]
6856.922
[2]
0.584314
[3]
489
[4]
0.078196
[5]
38.68543
[6]
108.4209
[22] array · 7 items
[0]
YWHAZ
[1]
7172.03
[2]
0.576243
[3]
473
[4]
0.075107
[5]
50.46931
[6]
118.5144
[23] array · 7 items
[0]
NPM1
[1]
8227.16
[2]
0.588268
[3]
469
[4]
0.096871
[5]
65.23567
[6]
160.9559
[24] array · 7 items
[0]
ITGA4
[1]
7832.164
[2]
0.586944
[3]
466
[4]
0.085024
[5]
44.23226
[6]
116.7656
[25] array · 7 items
[0]
GRB2
[1]
5536.105
[2]
0.555674
[3]
463
[4]
0.051024
[5]
35.73333
[6]
73.91536
[26] array · 7 items
[0]
VCP
[1]
6197.81
[2]
0.563479
[3]
440
[4]
0.061805
[5]
40.44492
[6]
85.07729
[27] array · 7 items
[0]
CDC5L
[1]
4925.157
[2]
0.562264
[3]
423
[4]
0.060454
[5]
40.74786
[6]
86.73088
[28] array · 7 items
[0]
EP300
[1]
6009.564
[2]
0.562567
[3]
421
[4]
0.052032
[5]
41.77682
[6]
97.50255
[29] array · 7 items
[0]
VCAM1
[1]
6003.134
[2]
0.579444
[3]
420
[4]
0.079334
[5]
39.46341
[6]
97.94946
[30] array · 7 items
[0]
CCDC8
[1]
5004.908
[2]
0.56654
[3]
420
[4]
0.065573
[5]
33.0081
[6]
72.19039
[31] array · 7 items
[0]
FBXO6
[1]
4267.925
[2]
0.559549
[3]
405
[4]
0.058117
[5]
27.9417
[6]
57.70662
[32] array · 7 items
[0]
HNRNPU
[1]
5872.296
[2]
0.574339
[3]
400
[4]
0.08583
[5]
63
[6]
138.3799
[33] array · 7 items
[0]
BRCA1
[1]
6517.061
[2]
0.561054
[3]
396
[4]
0.049457
[5]
31.98253
[6]
75.49951
[34] array · 7 items
[0]
SNW1
[1]
6051.717
[2]
0.561961
[3]
396
[4]
0.05577
[5]
37.17672
[6]
82.74052
[35] array · 7 items
[0]
HSPA5
[1]
5837.462
[2]
0.565618
[3]
396
[4]
0.067442
[5]
44.8642
[6]
93.19859
[36] array · 7 items
[0]
TRAF6
[1]
6651.395
[2]
0.555674
[3]
392
[4]
0.041215
[5]
24.94762
[6]
59.68665
[37] array · 7 items
[0]
EED
[1]
4392.456
[2]
0.567465
[3]
388
[4]
0.070736
[5]
42.96016
[6]
93.1871
[38] array · 7 items
[0]
HDAC1
[1]
3202.844
[2]
0.549526
[3]
386
[4]
0.043028
[5]
39.17277
[6]
74.42252
[39] array · 7 items
[0]
HUWE1
[1]
6899.481
[2]
0.571507
[3]
381
[4]
0.067745
[5]
39.42424
[6]
95.38087
[40] array · 7 items
[0]
EWSR1
[1]
4716.752
[2]
0.552729
[3]
381
[4]
0.05213
[5]
32.06965
[6]
61.19216
[41] array · 7 items
[0]
HNRNPA1
[1]
3161.637
[2]
0.559549
[3]
376
[4]
0.070618
[5]
55.08036
[6]
99.03541
[42] array · 7 items
[0]
RPA1
[1]
4112.825
[2]
0.555082
[3]
374
[4]
0.056751
[5]
36.0566
[6]
68.20034
[43] array · 7 items
[0]
HSPA8
[1]
4735.245
[2]
0.560451
[3]
354
[4]
0.060211
[5]
41.54425
[6]
81.78843
[44] array · 7 items
[0]
UBE2I
[1]
4251.229
[2]
0.548082
[3]
353
[4]
0.040825
[5]
27.41304
[6]
52.01266
[45] array · 7 items
[0]
VHL
[1]
4526.61
[2]
0.553609
[3]
353
[4]
0.054592
[5]
29.57971
[6]
54.42804
[46] array · 7 items
[0]
CUL2
[1]
3517.477
[2]
0.561054
[3]
352
[4]
0.068893
[5]
40.7193
[6]
76.78246
[47] array · 7 items
[0]
RPA2
[1]
3277.309
[2]
0.550686
[3]
352
[4]
0.051589
[5]
30.05181
[6]
52.91248
[48] array · 7 items
[0]
YWHAQ
[1]
4217.219
[2]
0.552729
[3]
345
[4]
0.052153
[5]
33.845
[6]
61.33131
[49] array · 7 items
[0]
MDM2
[1]
5224.652
[2]
0.553316
[3]
344
[4]
0.048166
[5]
30.26108
[6]
59.62867
[50] array · 7 items
[0]
PARK2
[1]
5674.771
[2]
0.559549
[3]
342
[4]
0.053931
[5]
29.9417
[6]
66.59044
[51] array · 7 items
[0]
HIST1H3F
[1]
2098.438
[2]
0.556861
[3]
339
[4]
0.058623
[5]
48.64055
[6]
92.1532
[52] array · 7 items
[0]
HIST1H3A
[1]
2098.438
[2]
0.556861
[3]
339
[4]
0.058623
[5]
48.64055
[6]
92.1532
[53] array · 7 items
[0]
HIST1H3D
[1]
2098.438
[2]
0.556861
[3]
339
[4]
0.058623
[5]
48.64055
[6]
92.1532
[54] array · 7 items
[0]
HIST1H3G
[1]
2098.438
[2]
0.556861
[3]
339
[4]
0.058623
[5]
48.64055
[6]
92.1532
[55] array · 7 items
[0]
HIST1H3C
[1]
2098.438
[2]
0.556861
[3]
339
[4]
0.058623
[5]
48.64055
[6]
92.1532
[56] array · 7 items
[0]
HIST1H3I
[1]
2098.438
[2]
0.556861
[3]
339
[4]
0.058623
[5]
48.64055
[6]
92.1532
[57] array · 7 items
[0]
HIST1H3J
[1]
2098.438
[2]
0.556861
[3]
339
[4]
0.058623
[5]
48.64055
[6]
92.1532
[58] array · 7 items
[0]
HIST1H3E
[1]
2098.438
[2]
0.556861
[3]
339
[4]
0.058623
[5]
48.64055
[6]
92.1532
[59] array · 7 items
[0]
HIST1H3B
[1]
2098.438
[2]
0.556861
[3]
339
[4]
0.058623
[5]
48.64055
[6]
92.1532
[60] array · 7 items
[0]
HIST1H3H
[1]
2098.438
[2]
0.556861
[3]
339
[4]
0.058623
[5]
48.64055
[6]
92.1532
[61] array · 7 items
[0]
HDAC5
[1]
4650.054
[2]
0.565618
[3]
332
[4]
0.066067
[5]
37.55328
[6]
78.84761
[62] array · 7 items
[0]
EEF1A1
[1]
4669.956
[2]
0.560753
[3]
329
[4]
0.070422
[5]
47.2467
[6]
84.56732
[63] array · 7 items
[0]
HSPB1
[1]
2002.872
[2]
0.533777
[3]
327
[4]
0.037852
[5]
28.41007
[6]
38.56029
[64] array · 7 items
[0]
CREBBP
[1]
2243.336
[2]
0.539018
[3]
326
[4]
0.034659
[5]
36.86875
[6]
62.29731
[65] array · 7 items
[0]
CUL5
[1]
2082.417
[2]
0.551852
[3]
323
[4]
0.064059
[5]
43.43655
[6]
68.27214
[66] array · 7 items
[0]
RPA3
[1]
2151.833
[2]
0.543796
[3]
314
[4]
0.04598
[5]
29.25882
[6]
45.84844
[67] array · 7 items
[0]
U2AF2
[1]
3871.685
[2]
0.558052
[3]
310
[4]
0.05925
[5]
43.12844
[6]
86.10159
[68] array · 7 items
[0]
IKBKG
[1]
2045.93
[2]
0.536799
[3]
306
[4]
0.035822
[5]
27.27211
[6]
40.40291
[69] array · 7 items
[0]
YWHAG
[1]
2690.41
[2]
0.543512
[3]
303
[4]
0.045769
[5]
34.15476
[6]
53.60628
[70] array · 7 items
[0]
PAN2
[1]
3382.067
[2]
0.554787
[3]
302
[4]
0.062376
[5]
34.43333
[6]
60.47694
[71] array · 7 items
[0]
AR
[1]
3134.942
[2]
0.540415
[3]
300
[4]
0.031188
[5]
27.61146
[6]
48.51884
[72] array · 7 items
[0]
SRC
[1]
2442.609
[2]
0.534598
[3]
299
[4]
0.025456
[5]
25.61029
[6]
43.73683
[73] array · 7 items
[0]
SMURF1
[1]
3391.445
[2]
0.546646
[3]
296
[4]
0.045905
[5]
24.20556
[6]
41.60122
[74] array · 7 items
[0]
YWHAE
[1]
2110.936
[2]
0.542382
[3]
296
[4]
0.050186
[5]
38.06024
[6]
54.26133
[75] array · 7 items
[0]
IKBKE
[1]
2788.819
[2]
0.539855
[3]
294
[4]
0.03488
[5]
18.56962
[6]
31.93874
[76] array · 7 items
[0]
CTNNB1
[1]
4842.84
[2]
0.547507
[3]
291
[4]
0.039217
[5]
25.30939
[6]
49.85884
[77] array · 7 items
[0]
SUZ12
[1]
3175.214
[2]
0.548947
[3]
290
[4]
0.046405
[5]
31.03627
[6]
56.67218
[78] array · 7 items
[0]
AKT1
[1]
2149.736
[2]
0.534598
[3]
278
[4]
0.028894
[5]
23.78832
[6]
34.81879
[79] array · 7 items
[0]
FUS
[1]
2869.735
[2]
0.553022
[3]
277
[4]
0.061692
[5]
43.76119
[6]
71.4498
[80] array · 7 items
[0]
ARRB2
[1]
3047.877
[2]
0.54837
[3]
270
[4]
0.052508
[5]
29.98421
[6]
50.1614
[81] array · 7 items
[0]
MAPK1
[1]
1661.102
[2]
0.530249
[3]
267
[4]
0.027795
[5]
25.20472
[6]
36.14141
[82] array · 7 items
[0]
HSPA4
[1]
2869.613
[2]
0.5421
[3]
267
[4]
0.041526
[5]
28.74691
[6]
45.89033
[83] array · 7 items
[0]
RELA
[1]
2373.639
[2]
0.535421
[3]
265
[4]
0.030975
[5]
26.1049
[6]
40.14754
[84] array · 7 items
[0]
STAU1
[1]
2901.346
[2]
0.551268
[3]
265
[4]
0.057269
[5]
36.70408
[6]
61.5319
[85] array · 7 items
[0]
CUL4B
[1]
1886.888
[2]
0.542946
[3]
258
[4]
0.053202
[5]
38.61078
[6]
54.05284
[86] array · 7 items
[0]
BMI1
[1]
1681.993
[2]
0.535146
[3]
256
[4]
0.033908
[5]
23.49645
[6]
33.33627
[87] array · 7 items
[0]
SMAD2
[1]
1860.082
[2]
0.529442
[3]
256
[4]
0.025645
[5]
20.41322
[6]
29.0253
[88] array · 7 items
[0]
COMMD3-BMI1
[1]
1681.993
[2]
0.535146
[3]
256
[4]
0.033908
[5]
23.49645
[6]
33.33627
[89] array · 7 items
[0]
PARP1
[1]
2103.137
[2]
0.53874
[3]
256
[4]
0.046043
[5]
36.66879
[6]
50.39636
[90] array · 7 items
[0]
SMAD3
[1]
1986.411
[2]
0.533231
[3]
255
[4]
0.027245
[5]
25.03053
[6]
38.00191
[91] array · 7 items
[0]
YWHAB
[1]
1680.029
[2]
0.530519
[3]
255
[4]
0.031926
[5]
26.15079
[6]
35.30965
[92] array · 7 items
[0]
TARDBP
[1]
1933.812
[2]
0.545788
[3]
253
[4]
0.061576
[5]
49.70811
[6]
74.31153
[93] array · 7 items
[0]
RPS27A
[1]
3022.78
[2]
0.543512
[3]
253
[4]
0.051495
[5]
37.50867
[6]
55.10979
[94] array · 7 items
[0]
CLTC
[1]
2194.827
[2]
0.536523
[3]
250
[4]
0.039743
[5]
28.63265
[6]
44.31083
[95] array · 7 items
[0]
MYH9
[1]
1763.332
[2]
0.533504
[3]
250
[4]
0.03501
[5]
29.61029
[6]
45.29088
[96] array · 7 items
[0]
TUBB
[1]
2383.363
[2]
0.544363
[3]
249
[4]
0.04812
[5]
32.77457
[6]
50.91263
[97] array · 7 items
[0]
EZH2
[1]
1941.901
[2]
0.536799
[3]
248
[4]
0.040164
[5]
30.76471
[6]
43.82032
[98] array · 7 items
[0]
JUN
[1]
1296.69
[2]
0.527834
[3]
247
[4]
0.023482
[5]
25.16522
[6]
34.51743
[99] array · 7 items
[0]
FLNA
[1]
2329.567
[2]
0.537352
[3]
247
[4]
0.0397
[5]
31.22819
[6]
50.12443
[100] array · 7 items
[0]
RB1
[1]
1898.756
[2]
0.53133
[3]
246
[4]
0.027173
[5]
25.60769
[6]
37.52534
[101] array · 7 items
[0]
CDK1
[1]
1528.586
[2]
0.530789
[3]
245
[4]
0.033329
[5]
26.04724
[6]
35.02188
[102] array · 7 items
[0]
HDAC2
[1]
1782.979
[2]
0.536523
[3]
244
[4]
0.038497
[5]
36.54967
[6]
54.55134
[103] array · 7 items
[0]
UBL4A
[1]
2439.333
[2]
0.544079
[3]
244
[4]
0.054326
[5]
40.25434
[6]
56.65844
[104] array · 7 items
[0]
CDC37
[1]
1191.997
[2]
0.525441
[3]
244
[4]
0.026047
[5]
22.14019
[6]
28.04657
[105] array · 7 items
[0]
ACTB
[1]
2757.472
[2]
0.540975
[3]
243
[4]
0.041952
[5]
29.14465
[6]
44.85049
[106] array · 7 items
[0]
RPL10
[1]
1536.133
[2]
0.537075
[3]
243
[4]
0.054545
[5]
59.01935
[6]
75.56065
[107] array · 7 items
[0]
HNRNPK
[1]
2495.745
[2]
0.547219
[3]
239
[4]
0.057228
[5]
43.24862
[6]
65.25151
[108] array · 7 items
[0]
XRCC6
[1]
1638.875
[2]
0.535421
[3]
234
[4]
0.04306
[5]
30.7972
[6]
41.1287
[109] array · 7 items
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PCNA
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1721.649
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0.531871
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234
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0.036312
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26.9771
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36.49264
[110] array · 7 items
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PRKDC
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2304.506
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0.540135
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233
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0.046236
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31.32298
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45.2468
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111
locator
section[13]/table-wrap[1]#t0002
gaps array · 2 items
[0]
asset:data:geo:GSE5281 not downloaded
[1]
asset:data:geo:GSE5281 licence not read
analysis object · 4 fields
state
complete
methods array · 2 items
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id
method-1
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network_analysis
specific
ppi_network
label
Network / pathway analysis
dsl_operations array · 3 items
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build_graph
[1]
centrality_scores
[2]
pathway_enrich
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data_shapes array · 1 item
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edge_list
evidence object · 3 fields
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0.7
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medium
quote
Protein-protein interaction
[1] object · 10 fields
id
method-2
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network_analysis
specific
pathway_enrichment
label
Network / pathway analysis
dsl_operations array · 1 item
[0]
pathway_enrich
missing_operations array · 0 items
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data_shapes array · 1 item
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edge_list
evidence object · 3 fields
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0.8
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high
quote
GO enrichment
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gaps array · 0 items
capability object · 3 fields
state
complete
requirements array · 1 item
[0] object · 6 fields
capability_id
capability:computational_analysis
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Computational analysis platform
assay_families array · 9 items
[0]
meta_analysis
[1]
machine_learning
[2]
survival_analysis
[3]
statistical_regression
[4]
pca
[5]
molecular_docking
[6]
network_analysis
[7]
differential_expression
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gwas
candidate
Automated Assays Laravel application and simulated adapters
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readiness object · 8 fields
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complete
tier
R1
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nothing:replicable_now
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true
required_operations array · 3 items
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build_graph
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centrality_scores
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pathway_enrich
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basis
The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: ppi_network.
capability object · 4 fields
tier
R1
capability_id
capability:computational_analysis
availability_state
owned
basis
The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here.
data object · 6 fields
tier
R1
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true
accessions array · 1 item
[0]
GSE5281
resolved_accessions array · 1 item
[0]
GSE5281
statements array · 1 item
[0]
Expression profiling data from GSE5281 were downloaded from the GEO database (http://www.ncbi.nlm.nih.gov/geo/) based on the microarray platform GPL570 (Affymetrix Human Gene Expression Array), which contained 74 samples from healthy individuals and 87 AD samples.
basis
The paper names GSE5281 in Gene Expression Omnibus (GEO) database and the accession resolves in the repository. No dataset was downloaded and no licence was read.
can_run object · 3 fields
dsl_operations array · 3 items
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build_graph
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assets array · 4 items
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source:pmid:33116763
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asset:table:pmid:33116763:1
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asset:table:pmid:33116763:2
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run_analysis
must_build object · 5 fields
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data_gaps array · 1 item
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data:geo:GSE5281
gaps array · 0 items
review object · 5 fields
state
partial
machine_critique object · 5 fields
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extraction_review
reader object · 5 fields
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MiniMax-M3.1-Flash
provider
minimax
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minimax
read_at
2026-10-31T19:14:08Z
independence
single_reader
evidence_check object · 2 fields
method
null
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null
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3
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20522
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590
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528
stages array · 1 item
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extraction
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complete
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MiniMax-M3.1-Flash
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minimax
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review.human_critique
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null
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execution.not_run
provenance object · 7 fields
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pmid:33116763
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paper
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pmid:33116763
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source:pmid:33116763
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manuscript
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PMID 33116763 full text
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data:geo:GSE5281
type
dataset
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GEO GSE5281
activities array · 3 items
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id
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classification
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paper
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pmid:33116763
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source:pmid:33116763
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manuscript
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PMID 33116763 full text
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data:geo:GSE5281
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dataset
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GEO GSE5281
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agent:corpus-assay-engine
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activity-read-33116763
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extraction
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source:pmid:33116763
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agent:minimax-reader
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activity-resolve-GSE5281
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accession_resolution
used array · 1 item
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data:geo:GSE5281
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agent:corpus-assay-engine
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agent:corpus-assay-engine
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software
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agent:minimax-reader
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MiniMax literature reader
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343fb30756ba6ec3
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pmid:33116763
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sha256:0e4626d175ffc54d3e3ab0022ec07f68e98b76a3d27de625b46d32430cbf2cd4
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null
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data_generation
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apoptosis_assay
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99e1195c7d6f
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99e1195c7d6f
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[0]
ing pathway, ubiquitin-mediated proteolysis, apoptosis and the NF-kappa B signaling pathway were si
[1]
liferation, ubiquitin-proteasome system, and apoptosis.Figure 5Go analysis of core targets. (A) Bio
[2]
ing pathway, ubiquitin-mediated proteolysis, apoptosis and NF-kappa B signaling pathway, and p53 si
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paper_text_order:1704
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33116763", "kind": "science-record", "revision": 8, "content_hash": "sha256:b26dae2764c01414daed0ac106d183f29c9aeef70050ae158e94cc8102ca4774", "created_at": "2026-11-01T15:41:14Z", "updated_at": "2026-11-01T22:02:25Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identifying the Mechanisms and Molecular Targets of Yizhiqingxin Formula on Alzheimer's Disease: Coupling Network Pharmacology with GEO Database.", "doi": "10.2147/PGPM.S269726", "pmid": "33116763", "authors": ["Tingting Zhang", "Linlin Pan", "Yu Cao", "Nanyang Liu", "Wei Wei", "Hao Li"], "journal": "Pharmacogenomics and personalized medicine", "year": 2020, "abstract": "BACKGROUND: Yizhiqingxin formula (YZQX) is a promising formula for the treatment of Alzheimer's disease (AD) with significant clinical effects. Here, we coupled a network pharmacology approach with the Gene Expression Omnibus (GEO) database to illustrate comprehensive mechanisms and screen for molecular targets of YZQX for AD treatment.\nMETHODS: First, active ingredients of YZQX were screened for the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database with the absorption, distribution, metabolism, and excretion (ADME) parameters. Subsequently, putative targets of active ingredients were predicted using the DrugBank database. AD-related targets were retrieved by analyzing published microarray data (accession number GSE5281). Protein-protein interaction (PPI) networks of YZQX putative targets and AD-related targets were constructed visually and merged to identify candidate targets for YZQX against AD using Cytoscape 3.7.2 software. We performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to further clarify the biological functions of the candidate targets. The gene-pathway network was established to filter for key target genes.\nRESULTS: Forty-three active ingredients were identified, and 193 putative target genes were predicted. Seven hundred and ten targets related to AD were screened with |log2 FC| > 1 and P < 0.05. Based on the PPI network, 110 target genes of YZQX against AD were identified. Moreover, 32 related pathways including the PI3K-Akt signaling pathway, MAPK signaling pathway, ubiquitin-mediated proteolysis, apoptosis and the NF-kappa B signaling pathway were significantly enriched. In the gene-pathway network, MAPK1, AKT1, TP53, MDM2, EGFR, RELA, SRC, GRB2, CUL1, and MYC targets are putative core genes for YZQX in AD treatment.\nCONCLUSION: YZQX against AD may exert its neuroprotective effect via the PI3K-Akt signaling pathway, MAPK signaling pathway, and ubiquitin-mediated proteolysis. YZQX may be a promising drug that can be used in the treatment of AD.", "claims": [{"id": "claim-data-access", "statement": "Expression profiling data from GSE5281 were downloaded from the GEO database (http://www.ncbi.nlm.nih.gov/geo/) based on the microarray platform GPL570 (Affymetrix Human Gene Expression Array), which contained 74 samples from healthy individuals and 87 AD samples.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33116763", "locator": "sections[5] \"Differentially Expressed Gene Search, Identification, and Analysis\" paragraph 2", "quote": "Expression profiling data from GSE5281 were downloaded from the GEO database (http://www.ncbi.nlm.nih.gov/geo/) based on the microarray platform GPL570 (Affymetrix Human Gene Expression Array), which contained 74 samples from healthy individuals and 87 AD samples."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:33116763"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE5281"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE5281"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33116763", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.2147/PGPM.S269726", "sha256": 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"row_count": 44, "column_count": 5, "numeric_cells": 129, "header_rows": 1, "locator": "section[10]/table-wrap[1]#t0001"}}, {"id": "asset:table:pmid:33116763:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:fcd0caf43d3cb9420aff8a158ad73106fd9d1e39f07743656436b8260b408557", "bytes": 8018, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[1]#t0002", "version": null, "note": "The Key Parameter Values of 110 Core Targets", "structure": {"pmcid": "PMC7571582", "section_index": 13, "section_title": "PPI Network Construction, Merging, and Analysis", "row_count": 111, "column_count": 7}, "table": {"label": "Table 2", "caption": "The Key Parameter Values of 110 Core Targets", "rows": [["Genes", "Betweenness", "Closeness", "Degree", "Eigenvector", "LAC", "Network"], ["NTRK1", "34,826.18", "0.664755", "1289", "0.116813", "53.29151", "277.6773"], ["CUL3", "21,198.02", "0.635588", "826", "0.114035", "56.47758", "229.5985"], ["APP", "10,243.13", "0.566848", "806", "0.055436", "28.96356", "72.53909"], ["HSP90AA1", "9460.703", "0.576881", "767", "0.067672", "43.58423", "114.5966"], ["EGFR", "9542.414", "0.570569", "744", "0.053291", "33.77992", "95.67655"], ["TP53", "19,385.39", "0.613891", "705", "0.093969", "51.64691", "187.0632"], ["ESR1", "15,416", "0.601847", "688", "0.088586", "47.31073", "153.2738"], ["XPO1", "9759.544", "0.57182", "687", "0.062664", "34.92015", "89.52947"], ["MCM2", "14,459.25", "0.613169", "651", "0.104016", "55.49354", "184.1087"], ["HSP90AB1", "7073.427", "0.567774", "640", "0.064062", "40.888", "93.63328"], ["FN1", "12,720.53", "0.607809", "635", "0.097986", "47.78167", "159.2176"], ["CDK2", "13,079.84", "0.59977", "622", "0.090112", "45.10315", "142.7661"], ["UBC", "12,601.12", "0.585626", "614", "0.071026", "43.33876", "131.519"], ["COPS5", "8276.179", "0.592951", "613", "0.094499", "54.41768", "148.6378"], ["CUL1", "8951.929", "0.593288", "564", "0.094188", "55.54103", "152.807"], ["CUL7", "9990.143", "0.599425", "552", "0.089742", "43.08069", "136.2477"], ["RNF2", "9862.539", "0.584641", "525", "0.074703", "37.84158", "110.2017"], ["CAND1", "6260.668", "0.582682", "508", "0.090651", "58.54333", "146.2511"], ["MYC", "5971.691", "0.55985", "503", "0.048495", "29.34222", "67.73357"], ["SIRT7", "6146.117", "0.569013", "496", "0.067372", "34.51938", "80.48613"], ["OBSL1", "6856.922", "0.584314", "489", "0.078196", "38.68543", "108.4209"], ["YWHAZ", "7172.03", "0.576243", "473", "0.075107", "50.46931", "118.5144"], ["NPM1", "8227.16", "0.588268", "469", "0.096871", "65.23567", "160.9559"], ["ITGA4", "7832.164", "0.586944", "466", "0.085024", "44.23226", "116.7656"], ["GRB2", "5536.105", "0.555674", "463", "0.051024", "35.73333", "73.91536"], ["VCP", "6197.81", "0.563479", "440", "0.061805", "40.44492", "85.07729"], ["CDC5L", "4925.157", "0.562264", "423", "0.060454", "40.74786", "86.73088"], ["EP300", "6009.564", "0.562567", "421", "0.052032", "41.77682", "97.50255"], ["VCAM1", "6003.134", "0.579444", "420", "0.079334", "39.46341", "97.94946"], ["CCDC8", "5004.908", "0.56654", "420", "0.065573", "33.0081", "72.19039"], ["FBXO6", "4267.925", "0.559549", "405", "0.058117", "27.9417", "57.70662"], ["HNRNPU", "5872.296", "0.574339", "400", "0.08583", "63", "138.3799"], ["BRCA1", "6517.061", "0.561054", "396", "0.049457", "31.98253", "75.49951"], ["SNW1", "6051.717", "0.561961", "396", "0.05577", "37.17672", "82.74052"], ["HSPA5", "5837.462", "0.565618", "396", "0.067442", "44.8642", "93.19859"], ["TRAF6", "6651.395", "0.555674", "392", "0.041215", "24.94762", "59.68665"], ["EED", "4392.456", "0.567465", "388", "0.070736", "42.96016", "93.1871"], ["HDAC1", "3202.844", "0.549526", "386", "0.043028", "39.17277", "74.42252"], ["HUWE1", "6899.481", "0.571507", "381", "0.067745", "39.42424", "95.38087"], ["EWSR1", "4716.752", "0.552729", "381", "0.05213", "32.06965", "61.19216"], ["HNRNPA1", "3161.637", "0.559549", "376", "0.070618", "55.08036", "99.03541"], ["RPA1", "4112.825", "0.555082", "374", "0.056751", "36.0566", "68.20034"], ["HSPA8", "4735.245", "0.560451", "354", "0.060211", "41.54425", "81.78843"], ["UBE2I", "4251.229", "0.548082", "353", "0.040825", "27.41304", "52.01266"], ["VHL", "4526.61", "0.553609", "353", "0.054592", "29.57971", "54.42804"], ["CUL2", "3517.477", "0.561054", "352", "0.068893", "40.7193", "76.78246"], ["RPA2", "3277.309", "0.550686", "352", "0.051589", "30.05181", "52.91248"], ["YWHAQ", "4217.219", "0.552729", "345", "0.052153", "33.845", "61.33131"], ["MDM2", "5224.652", "0.553316", "344", "0.048166", "30.26108", "59.62867"], ["PARK2", "5674.771", "0.559549", "342", "0.053931", "29.9417", "66.59044"], ["HIST1H3F", "2098.438", "0.556861", "339", "0.058623", "48.64055", "92.1532"], ["HIST1H3A", "2098.438", "0.556861", "339", "0.058623", "48.64055", "92.1532"], ["HIST1H3D", "2098.438", "0.556861", "339", "0.058623", "48.64055", "92.1532"], ["HIST1H3G", "2098.438", "0.556861", "339", "0.058623", "48.64055", "92.1532"], ["HIST1H3C", "2098.438", "0.556861", "339", "0.058623", "48.64055", "92.1532"], ["HIST1H3I", "2098.438", "0.556861", "339", "0.058623", "48.64055", "92.1532"], ["HIST1H3J", "2098.438", "0.556861", "339", "0.058623", "48.64055", "92.1532"], ["HIST1H3E", "2098.438", "0.556861", "339", "0.058623", "48.64055", "92.1532"], ["HIST1H3B", "2098.438", "0.556861", "339", "0.058623", "48.64055", "92.1532"], ["HIST1H3H", "2098.438", "0.556861", "339", "0.058623", "48.64055", "92.1532"], ["HDAC5", "4650.054", "0.565618", "332", "0.066067", "37.55328", "78.84761"], ["EEF1A1", "4669.956", "0.560753", "329", "0.070422", "47.2467", "84.56732"], ["HSPB1", "2002.872", "0.533777", "327", "0.037852", "28.41007", "38.56029"], ["CREBBP", "2243.336", "0.539018", "326", "0.034659", "36.86875", "62.29731"], ["CUL5", "2082.417", "0.551852", "323", "0.064059", "43.43655", "68.27214"], ["RPA3", "2151.833", "0.543796", "314", "0.04598", "29.25882", "45.84844"], ["U2AF2", "3871.685", "0.558052", "310", "0.05925", "43.12844", "86.10159"], ["IKBKG", "2045.93", "0.536799", "306", "0.035822", "27.27211", "40.40291"], ["YWHAG", "2690.41", "0.543512", "303", "0.045769", "34.15476", "53.60628"], ["PAN2", "3382.067", "0.554787", "302", "0.062376", "34.43333", "60.47694"], ["AR", "3134.942", "0.540415", "300", "0.031188", "27.61146", "48.51884"], ["SRC", "2442.609", "0.534598", "299", "0.025456", "25.61029", "43.73683"], ["SMURF1", "3391.445", "0.546646", "296", "0.045905", "24.20556", "41.60122"], ["YWHAE", "2110.936", "0.542382", "296", "0.050186", "38.06024", "54.26133"], ["IKBKE", "2788.819", "0.539855", "294", "0.03488", "18.56962", "31.93874"], ["CTNNB1", "4842.84", "0.547507", "291", "0.039217", "25.30939", "49.85884"], ["SUZ12", "3175.214", "0.548947", "290", "0.046405", "31.03627", "56.67218"], ["AKT1", "2149.736", "0.534598", "278", "0.028894", "23.78832", "34.81879"], ["FUS", "2869.735", "0.553022", "277", "0.061692", "43.76119", "71.4498"], ["ARRB2", "3047.877", "0.54837", "270", "0.052508", "29.98421", "50.1614"], ["MAPK1", "1661.102", "0.530249", "267", "0.027795", "25.20472", "36.14141"], ["HSPA4", "2869.613", "0.5421", "267", "0.041526", "28.74691", "45.89033"], ["RELA", "2373.639", "0.535421", "265", "0.030975", "26.1049", "40.14754"], ["STAU1", "2901.346", "0.551268", "265", "0.057269", "36.70408", "61.5319"], ["CUL4B", "1886.888", "0.542946", "258", "0.053202", "38.61078", "54.05284"], ["BMI1", "1681.993", "0.535146", "256", "0.033908", "23.49645", "33.33627"], ["SMAD2", "1860.082", "0.529442", "256", "0.025645", "20.41322", "29.0253"], ["COMMD3-BMI1", "1681.993", "0.535146", "256", "0.033908", "23.49645", "33.33627"], ["PARP1", "2103.137", "0.53874", "256", "0.046043", "36.66879", "50.39636"], ["SMAD3", "1986.411", "0.533231", "255", "0.027245", "25.03053", "38.00191"], ["YWHAB", "1680.029", "0.530519", "255", "0.031926", "26.15079", "35.30965"], ["TARDBP", "1933.812", "0.545788", "253", "0.061576", "49.70811", "74.31153"], ["RPS27A", "3022.78", "0.543512", "253", "0.051495", "37.50867", "55.10979"], ["CLTC", "2194.827", "0.536523", "250", "0.039743", "28.63265", "44.31083"], ["MYH9", "1763.332", "0.533504", "250", "0.03501", "29.61029", "45.29088"], ["TUBB", "2383.363", "0.544363", "249", "0.04812", "32.77457", "50.91263"], ["EZH2", "1941.901", "0.536799", "248", "0.040164", "30.76471", "43.82032"], ["JUN", "1296.69", "0.527834", "247", "0.023482", "25.16522", "34.51743"], ["FLNA", "2329.567", "0.537352", "247", "0.0397", "31.22819", "50.12443"], ["RB1", "1898.756", "0.53133", "246", "0.027173", "25.60769", "37.52534"], ["CDK1", "1528.586", "0.530789", "245", "0.033329", "26.04724", "35.02188"], ["HDAC2", "1782.979", "0.536523", "244", "0.038497", "36.54967", "54.55134"], ["UBL4A", "2439.333", "0.544079", "244", "0.054326", "40.25434", "56.65844"], ["CDC37", "1191.997", "0.525441", "244", "0.026047", "22.14019", "28.04657"], ["ACTB", "2757.472", "0.540975", "243", "0.041952", "29.14465", "44.85049"], ["RPL10", "1536.133", "0.537075", "243", "0.054545", "59.01935", "75.56065"], ["HNRNPK", "2495.745", "0.547219", "239", "0.057228", "43.24862", "65.25151"], ["XRCC6", "1638.875", "0.535421", "234", "0.04306", "30.7972", "41.1287"], ["PCNA", "1721.649", "0.531871", "234", "0.036312", "26.9771", "36.49264"], ["PRKDC", "2304.506", "0.540135", "233", "0.046236", "31.32298", "45.2468"]], "row_count": 111, "column_count": 7, "numeric_cells": 668, "header_rows": 1, "locator": "section[13]/table-wrap[1]#t0002"}}], "gaps": ["asset:data:geo:GSE5281 not downloaded", "asset:data:geo:GSE5281 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": 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"blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: ppi_network."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE5281"], "resolved_accessions": ["GSE5281"], "statements": ["Expression profiling data from GSE5281 were downloaded from the GEO database (http://www.ncbi.nlm.nih.gov/geo/) based on the microarray platform GPL570 (Affymetrix Human Gene Expression Array), which contained 74 samples from healthy individuals and 87 AD samples."], "basis": "The paper names GSE5281 in Gene Expression Omnibus (GEO) database and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "assets": ["source:pmid:33116763", "data:geo:GSE5281", "asset:table:pmid:33116763:1", "asset:table:pmid:33116763:2"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE5281"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T19:14:08Z", "independence": "single_reader"}, "evidence_check": {"method": null, "availability": null}, "calls": 3, "usage": {"prompt_tokens": 20522, "completion_tokens": 590, "cached_tokens": 528}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:33116763", "type": "paper", "label": "pmid:33116763"}, {"id": "source:pmid:33116763", "type": "manuscript", "label": "PMID 33116763 full text"}, {"id": "data:geo:GSE5281", "type": "dataset", "label": "GEO GSE5281"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:33116763", "type": "paper", "label": "pmid:33116763"}, {"id": "source:pmid:33116763", "type": "manuscript", "label": "PMID 33116763 full text"}, {"id": "data:geo:GSE5281", "type": "dataset", "label": "GEO GSE5281"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-33116763", "type": "extraction", "used": ["source:pmid:33116763"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE5281", "type": "accession_resolution", "used": ["data:geo:GSE5281"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:33116763", "parent_hash": "sha256:0e4626d175ffc54d3e3ab0022ec07f68e98b76a3d27de625b46d32430cbf2cd4", "fork_of": null, "generation": 7}, "gaps": ["asset:data:geo:GSE5281 licence not read", "asset:data:geo:GSE5281 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ing pathway, ubiquitin-mediated proteolysis, apoptosis and the NF-kappa B signaling pathway were si", "liferation, ubiquitin-proteasome system, and apoptosis.Figure 5Go analysis of core targets. 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