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pmid:35468096

Effective biomarkers and therapeutic targets of nerve-immunity interaction in the treatment of depression: an integrated investigation of the miRNA-mRNA regulatory networks.

Zixuan Wu · Zhixiang Cai · Hongshuo Shi · Xuyan Huang · Minjie Cai · Kai Yuan · Peidong Huang · Guoqi Shi · Tao Yan · Zhichao Li

Aging · 2022 doi:10.18632/aging.204030

Paper

complete

Experiment

complete

Data

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Analysis

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Execution

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title
Effective biomarkers and therapeutic targets of nerve-immunity interaction in the treatment of depression: an integrated investigation of the miRNA-mRNA regulatory networks.
doi
10.18632/aging.204030
pmid
35468096
authors array · 10 items
[0]
Zixuan Wu
[1]
Zhixiang Cai
[2]
Hongshuo Shi
[3]
Xuyan Huang
[4]
Minjie Cai
[5]
Kai Yuan
[6]
Peidong Huang
[7]
Guoqi Shi
[8]
Tao Yan
[9]
Zhichao Li
journal
Aging
year
2022
abstract
BACKGROUND: Major depressive disorder (MDD) is an emotional condition that interferes with sufferers' work and daily life. Numerous studies have found that miRNAs play a significant role in the development of MDD and can be utilized as a biomarker for its diagnosis and therapy. However, there have been few studies on nerve-immunity interaction treatment for the brains of MMD patients. METHODS: The work is performed on microarray data. We analyzed the differences of miRNAs (GSE58105, GSE81152, GSE152267, and GSE182194) and mRNA (GSE19738, GSE32280, GSE44593, GSE53987, and GSE98793) in MDD and healthy samples from GEO datasets. FunRich was used to predict the transcription factors and target genes of the miRNAs, and TF and GO enrichment analyses were performed. Then, by comparing the differential expression of the anticipated target genes and five mRNAs, intersecting mRNAs were discovered. The intersecting genes were submitted to GO and KEGG analyses to determine their functions. These intersecting potential genes and pathways that linked to MDD in neurological and immunological aspects have been identified for future investigation. RESULTS: We discovered five hub genes: KCND2, MYT1L, GJA1, CHL1, and SNAP25, which were all up-regulated genes. However, in MMD, the equivalent miRNAs, hsa-miR-206 and hsa-miR-338-3p, were both down-regulated. These miRNAs can activate or inhibit the T cell receptor signal pathway, JAK-STAT and other signal pathways, govern immune-inflammatory response, neuronal remodeling, and mediate the onset and development of MMD Conclusions: The results of a thorough bioinformatics investigation of miRNAs and mRNAs in MDD showed that miR-338-3P and miR-206 might be effective biomarkers and possible therapeutic targets for the treatment of MDD via nerve-immunity interaction.
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Genes acquired by the Limma software were determined to be significantly differentially expressed miRNAs using the corrected miRNA chip dataset and log2 (fold change) >2 or log2 (fold change) <−2 as screening thresholds (DE-miRNAs).
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Genes acquired by the Limma software were determined to be significantly differentially expressed miRNAs using the corrected miRNA chip dataset and log2 (fold change) >2 or log2 (fold change) <−2 as screening thresholds (DE-miRNAs).
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The datasets generated during and/or analyzed during the current study are available in the [GEO] repository, https://www.ncbi.nlm.nih.gov/geo/. The datasets generated during and/or analyzed during the current study are available from Supplementary.
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The integrated analysis identified 34 DE-miRNAs and 386 DE-mRNAs in MDD and healthy-control datasets.
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The combined dataset of 42 healthy people and 88 MMD patients revealed 34 DE-miRNAs (20 up-regulated and 14 down-regulated), following the screening with P < 0.05 and log2 (fold change) ≥2.
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sections[14] "Identification of DE-miRNAs and DE-mRNAs" paragraph 2
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The combined dataset of 42 healthy people and 88 MMD patients revealed 34 DE-miRNAs (20 up-regulated and 14 down-regulated), following the screening with P < 0.05 and log2 (fold change) ≥2.
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sections[14] "Identification of DE-miRNAs and DE-mRNAs" paragraph 2
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A total of 386 DE-mRNAs were identified after screening with P < 0.05 and log2(fold change) ≥2 (181up-regulated and 205 down-regulated).
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[29]
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[30]
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[31]
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[32]
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[33]
GSM1304885
[34]
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[35]
GSM1304887
[36]
GSM1304888
[37]
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[38]
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[39]
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[40]
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[41]
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[42]
GSM1304894
[43]
GSM1304895
[44]
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[45]
GSM1304897
[46]
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[47]
GSM1304899
[48]
GSM1304900
[49]
GSM1304901
[50]
GSM1304902
[51]
GSM1304903
[52]
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[53]
GSM1304905
[54]
GSM1304906
[55]
GSM1304907
[56]
GSM1304908
[57]
GSM1304909
[58]
GSM1304910
[59]
GSM1304911
[60]
GSM1304912
[61]
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[62]
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[63]
GSM1304915
[64]
GSM1304916
[65]
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[66]
GSM1304918
[67]
GSM1304919
[68]
GSM1304920
[69]
GSM1304921
[70]
GSM1304922
[71]
GSM1304923
[72]
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[73]
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[74]
GSM1304926
[75]
GSM1304927
[76]
GSM1304928
[77]
GSM1304929
[78]
GSM1304930
[79]
GSM1304931
[80]
GSM1304932
[81]
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[82]
GSM1304934
[83]
GSM1304935
[84]
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[85]
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[86]
GSM1304938
[87]
GSM1304939
[88]
GSM1304940
[89]
GSM1304941
[90]
GSM1304942
[91]
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[92]
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[93]
GSM1304945
[94]
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[95]
GSM1304947
[96]
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[97]
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[98]
GSM1304950
[99]
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[100]
GSM1304952
[101]
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[102]
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[103]
GSM1304955
[104]
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[105]
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[106]
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[107]
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[108]
GSM1304960
[109]
GSM1304961
[110]
GSM1304962
[111]
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[112]
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[113]
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[114]
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[115]
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[116]
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[117]
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[118]
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[119]
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[120]
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[121]
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[122]
GSM1304974
[123]
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[124]
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[125]
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[126]
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[127]
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[128]
GSM1304980
[129]
GSM1304981
[130]
GSM1304982
[131]
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[132]
GSM1304984
[133]
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[134]
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[135]
GSM1304987
[136]
GSM1304988
[137]
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[138]
GSM1304990
[139]
GSM1304991
[140]
GSM1304992
[141]
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[142]
GSM1304994
[143]
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[144]
GSM1304996
[145]
GSM1304997
[146]
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[147]
GSM1304999
[148]
GSM1305000
[149]
GSM1305001
[150]
GSM1305002
[151]
GSM1305003
[152]
GSM1305004
[153]
GSM1305005
[154]
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[155]
GSM1305007
[156]
GSM1305008
[157]
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[158]
GSM1305010
[159]
GSM1305011
[160]
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[161]
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[162]
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[163]
GSM1305015
[164]
GSM1305016
[165]
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[166]
GSM1305018
[167]
GSM1305019
[168]
GSM1305020
[169]
GSM1305021
[170]
GSM1305022
[171]
GSM1305023
[172]
GSM1305024
[173]
GSM1305025
[174]
GSM1305026
[175]
GSM1305027
[176]
GSM1305028
[177]
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[178]
GSM1305030
[179]
GSM1305031
[180]
GSM1305032
[181]
GSM1305033
[182]
GSM1305034
[183]
GSM1305035
[184]
GSM1305036
[185]
GSM1305037
[186]
GSM1305038
[187]
GSM1305039
[188]
GSM1305040
[189]
GSM1305041
[190]
GSM1305042
[191]
GSM1305043
[192]
GSM1305044
[193]
GSM1305045
[194]
GSM1305046
[195]
GSM1305047
[196]
GSM1305048
[197]
GSM1305049
[198]
GSM1305050
[199]
GSM1305051
[200]
GSM1305052
[201]
GSM1305053
[202]
GSM1305054
[203]
GSM1305055
[204]
GSM1305056
sample_count
205
group_sizes
null
group_sizes_basis
null
platform
570
taxon
Homo sapiens
title
Microarray profiling of PFC, HPC and STR from subjects with schizophrenia, bipolar, MDD or control
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[7] object · 15 fields
id
data:geo:GSE58105
role
raw
format
geo-series
media_type
application/vnd.ncbi.geo-series+json
uri
https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE58105
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
GSE58105
version
null
note
The datasets generated during and/or analyzed during the current study are available in the [GEO] repository, https://www.ncbi.nlm.nih.gov/geo/. The datasets generated during and/or analyzed during the current study are available from Supplementary.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The datasets generated during and/or analyzed during the current study are available in the [GEO] repository, https://www.ncbi.nlm.nih.gov/geo/. The datasets generated during and/or analyzed during the current study are available from Supplementary.
access_statement_kind
data_availability_statement
sample_accessions array · 25 items
[0]
GSM1400871
[1]
GSM1400872
[2]
GSM1400873
[3]
GSM1400874
[4]
GSM1400875
[5]
GSM1400876
[6]
GSM1400877
[7]
GSM1400878
[8]
GSM1400879
[9]
GSM1400880
[10]
GSM1400881
[11]
GSM1400882
[12]
GSM1400883
[13]
GSM1400884
[14]
GSM1400885
[15]
GSM1400886
[16]
GSM1400887
[17]
GSM1400888
[18]
GSM1400889
[19]
GSM1400890
[20]
GSM1400891
[21]
GSM1400892
[22]
GSM1400893
[23]
GSM1400894
[24]
GSM1400895
sample_count
25
group_sizes
null
group_sizes_basis
null
platform
18743
taxon
Homo sapiens
title
Prefrontal cortex microRNA expression profiling in major depression
resolution_checked_at
2026-11-01T18:06:44Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[8] object · 15 fields
id
data:geo:GSE81152
role
raw
format
geo-series
media_type
application/vnd.ncbi.geo-series+json
uri
https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE81152
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
GSE81152
version
null
note
The datasets generated during and/or analyzed during the current study are available in the [GEO] repository, https://www.ncbi.nlm.nih.gov/geo/. The datasets generated during and/or analyzed during the current study are available from Supplementary.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The datasets generated during and/or analyzed during the current study are available in the [GEO] repository, https://www.ncbi.nlm.nih.gov/geo/. The datasets generated during and/or analyzed during the current study are available from Supplementary.
access_statement_kind
data_availability_statement
sample_accessions array · 80 items
[0]
GSM2143700
[1]
GSM2143701
[2]
GSM2143702
[3]
GSM2143703
[4]
GSM2143704
[5]
GSM2143705
[6]
GSM2143706
[7]
GSM2143707
[8]
GSM2143708
[9]
GSM2143709
[10]
GSM2143710
[11]
GSM2143711
[12]
GSM2143712
[13]
GSM2143713
[14]
GSM2143714
[15]
GSM2143715
[16]
GSM2143716
[17]
GSM2143717
[18]
GSM2143718
[19]
GSM2143719
[20]
GSM2143720
[21]
GSM2143721
[22]
GSM2143722
[23]
GSM2143723
[24]
GSM2143724
[25]
GSM2143725
[26]
GSM2143726
[27]
GSM2143727
[28]
GSM2143728
[29]
GSM2143729
[30]
GSM2143730
[31]
GSM2143731
[32]
GSM2143732
[33]
GSM2143733
[34]
GSM2143734
[35]
GSM2143735
[36]
GSM2143736
[37]
GSM2143737
[38]
GSM2143738
[39]
GSM2143739
[40]
GSM2143740
[41]
GSM2143741
[42]
GSM2143742
[43]
GSM2143743
[44]
GSM2143744
[45]
GSM2143745
[46]
GSM2143746
[47]
GSM2143747
[48]
GSM2143748
[49]
GSM2143749
[50]
GSM2143750
[51]
GSM2143751
[52]
GSM2143752
[53]
GSM2143753
[54]
GSM2143754
[55]
GSM2143755
[56]
GSM2143756
[57]
GSM2143757
[58]
GSM2143758
[59]
GSM2143759
[60]
GSM2143760
[61]
GSM2143761
[62]
GSM2143762
[63]
GSM2143763
[64]
GSM2143764
[65]
GSM2143765
[66]
GSM2143766
[67]
GSM2143767
[68]
GSM2143768
[69]
GSM2143769
[70]
GSM2143770
[71]
GSM2143771
[72]
GSM2143772
[73]
GSM2143773
[74]
GSM2143774
[75]
GSM2143775
[76]
GSM2143776
[77]
GSM2143777
[78]
GSM2143778
[79]
GSM2143779
sample_count
80
group_sizes
null
group_sizes_basis
null
platform
21814
taxon
Homo sapiens
title
MicroRNAs as diagnostic biomarkers for major depression
resolution_checked_at
2026-11-01T18:06:44Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[9] object · 15 fields
id
data:geo:GSE98793
role
raw
format
geo-series
media_type
application/vnd.ncbi.geo-series+json
uri
https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE98793
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
GSE98793
version
null
note
The datasets generated during and/or analyzed during the current study are available in the [GEO] repository, https://www.ncbi.nlm.nih.gov/geo/. The datasets generated during and/or analyzed during the current study are available from Supplementary.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The datasets generated during and/or analyzed during the current study are available in the [GEO] repository, https://www.ncbi.nlm.nih.gov/geo/. The datasets generated during and/or analyzed during the current study are available from Supplementary.
access_statement_kind
data_availability_statement
sample_accessions array · 192 items
[0]
GSM2612096
[1]
GSM2612097
[2]
GSM2612098
[3]
GSM2612099
[4]
GSM2612100
[5]
GSM2612101
[6]
GSM2612102
[7]
GSM2612103
[8]
GSM2612104
[9]
GSM2612105
[10]
GSM2612106
[11]
GSM2612107
[12]
GSM2612108
[13]
GSM2612109
[14]
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[15]
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[16]
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[17]
GSM2612113
[18]
GSM2612114
[19]
GSM2612115
[20]
GSM2612116
[21]
GSM2612117
[22]
GSM2612118
[23]
GSM2612119
[24]
GSM2612120
[25]
GSM2612121
[26]
GSM2612122
[27]
GSM2612123
[28]
GSM2612124
[29]
GSM2612125
[30]
GSM2612126
[31]
GSM2612127
[32]
GSM2612128
[33]
GSM2612129
[34]
GSM2612130
[35]
GSM2612131
[36]
GSM2612132
[37]
GSM2612133
[38]
GSM2612134
[39]
GSM2612135
[40]
GSM2612136
[41]
GSM2612137
[42]
GSM2612138
[43]
GSM2612139
[44]
GSM2612140
[45]
GSM2612141
[46]
GSM2612142
[47]
GSM2612143
[48]
GSM2612144
[49]
GSM2612145
[50]
GSM2612146
[51]
GSM2612147
[52]
GSM2612148
[53]
GSM2612149
[54]
GSM2612150
[55]
GSM2612151
[56]
GSM2612152
[57]
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[58]
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[59]
GSM2612155
[60]
GSM2612156
[61]
GSM2612157
[62]
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[63]
GSM2612159
[64]
GSM2612160
[65]
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[66]
GSM2612162
[67]
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[68]
GSM2612164
[69]
GSM2612165
[70]
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[71]
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[72]
GSM2612168
[73]
GSM2612169
[74]
GSM2612170
[75]
GSM2612171
[76]
GSM2612172
[77]
GSM2612173
[78]
GSM2612174
[79]
GSM2612175
[80]
GSM2612176
[81]
GSM2612177
[82]
GSM2612178
[83]
GSM2612179
[84]
GSM2612180
[85]
GSM2612181
[86]
GSM2612182
[87]
GSM2612183
[88]
GSM2612184
[89]
GSM2612185
[90]
GSM2612186
[91]
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[92]
GSM2612188
[93]
GSM2612189
[94]
GSM2612190
[95]
GSM2612191
[96]
GSM2612192
[97]
GSM2612193
[98]
GSM2612194
[99]
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[100]
GSM2612196
[101]
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[102]
GSM2612198
[103]
GSM2612199
[104]
GSM2612200
[105]
GSM2612201
[106]
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[107]
GSM2612203
[108]
GSM2612204
[109]
GSM2612205
[110]
GSM2612206
[111]
GSM2612207
[112]
GSM2612208
[113]
GSM2612209
[114]
GSM2612210
[115]
GSM2612211
[116]
GSM2612212
[117]
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[118]
GSM2612214
[119]
GSM2612215
[120]
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[121]
GSM2612217
[122]
GSM2612218
[123]
GSM2612219
[124]
GSM2612220
[125]
GSM2612221
[126]
GSM2612222
[127]
GSM2612223
[128]
GSM2612224
[129]
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[130]
GSM2612226
[131]
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[132]
GSM2612228
[133]
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[134]
GSM2612230
[135]
GSM2612231
[136]
GSM2612232
[137]
GSM2612233
[138]
GSM2612234
[139]
GSM2612235
[140]
GSM2612236
[141]
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[142]
GSM2612238
[143]
GSM2612239
[144]
GSM2612240
[145]
GSM2612241
[146]
GSM2612242
[147]
GSM2612243
[148]
GSM2612244
[149]
GSM2612245
[150]
GSM2612246
[151]
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[152]
GSM2612248
[153]
GSM2612249
[154]
GSM2612250
[155]
GSM2612251
[156]
GSM2612252
[157]
GSM2612253
[158]
GSM2612254
[159]
GSM2612255
[160]
GSM2612256
[161]
GSM2612257
[162]
GSM2612258
[163]
GSM2612259
[164]
GSM2612260
[165]
GSM2612261
[166]
GSM2612262
[167]
GSM2612263
[168]
GSM2612264
[169]
GSM2612265
[170]
GSM2612266
[171]
GSM2612267
[172]
GSM2612268
[173]
GSM2612269
[174]
GSM2612270
[175]
GSM2612271
[176]
GSM2612272
[177]
GSM2612273
[178]
GSM2612274
[179]
GSM2612275
[180]
GSM2612276
[181]
GSM2612277
[182]
GSM2612278
[183]
GSM2612279
[184]
GSM2612280
[185]
GSM2612281
[186]
GSM2612282
[187]
GSM2612283
[188]
GSM2612284
[189]
GSM2612285
[190]
GSM2612286
[191]
GSM2612287
sample_count
192
group_sizes
null
group_sizes_basis
null
platform
570
taxon
Homo sapiens
title
Gene expression analysis in whole blood samples obtained from donors diagnosed with MDD compared to healthy controls
resolution_checked_at
2026-11-01T15:39:55Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
gaps array · 18 items
[0]
asset:data:geo:GSE152267 not downloaded
[1]
asset:data:geo:GSE152267 licence not read
[2]
asset:data:geo:GSE182194 not downloaded
[3]
asset:data:geo:GSE182194 licence not read
[4]
asset:data:geo:GSE19738 not downloaded
[5]
asset:data:geo:GSE19738 licence not read
[6]
asset:data:geo:GSE32280 not downloaded
[7]
asset:data:geo:GSE32280 licence not read
[8]
asset:data:geo:GSE44593 not downloaded
[9]
asset:data:geo:GSE44593 licence not read
[10]
asset:data:geo:GSE53987 not downloaded
[11]
asset:data:geo:GSE53987 licence not read
[12]
asset:data:geo:GSE58105 not downloaded
[13]
asset:data:geo:GSE58105 licence not read
[14]
asset:data:geo:GSE81152 not downloaded
[15]
asset:data:geo:GSE81152 licence not read
[16]
asset:data:geo:GSE98793 not downloaded
[17]
asset:data:geo:GSE98793 licence not read
analysis object · 4 fields
state
complete
methods array · 2 items
[0] object · 10 fields
id
method-1
family
differential_expression
specific
limma_voom
label
Differential expression analysis
dsl_operations array · 3 items
[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
count_matrix_with_condition
evidence object · 3 fields
score
1
band
verbatim
quote
Genes acquired by the Limma software were determined to be significantly differentially expressed miRNAs using the corrected miRNA chip dataset and log2 (fold change) >2 or log2 (fold change) <−2 as screening thresholds (DE-miRNAs).
[1] object · 10 fields
id
method-2
family
network_analysis
specific
pathway_enrichment
label
Network / pathway analysis
dsl_operations array · 1 item
[0]
pathway_enrich
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
edge_list
evidence object · 3 fields
score
0.7
band
medium
quote
GO enrichment
targets array · 1 item
[0] object · 8 fields
id
target-published-estimate
claim_id
claim-target-result
operation
differential_expression_fit
unit
p-value
tolerance
null
state
complete
note
The threshold the paper applied to its own result, as the paper states it. A run that reproduces the effect is judged against this threshold.
gaps array · 0 items
capability object · 3 fields
state
complete
requirements array · 1 item
[0] object · 6 fields
capability_id
capability:computational_analysis
label
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
[8]
gwas
candidate
Automated Assays Laravel application and simulated adapters
gaps array · 0 items
readiness object · 8 fields
state
complete
tier
R1
blocked_on
nothing:replicable_now
axes object · 3 fields
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GSE53987
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The datasets generated during and/or analyzed during the current study are available in the [GEO] repository, https://www.ncbi.nlm.nih.gov/geo/. The datasets generated during and/or analyzed during the current study are available from Supplementary.
basis
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patients. METHODS: The work is performed on microarray data. We analyzed the differences of miRNAs
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Genes acquired by the Limma software were determined to be significantly differentially expressed miRNAs using the corrected miRNA chip dataset and log2 (fold change) >2 or log2 (fold change) <−2 as screening thresholds (DE-miRNAs).
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35468096", "kind": "science-record", "revision": 5, "content_hash": "sha256:4f390d15a81222fd9e19a642cf0b747c6df04c5df45935d1af4a9f509f4b50e4", "created_at": "2026-11-01T18:14:20Z", "updated_at": "2026-11-01T22:48:55Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Effective biomarkers and therapeutic targets of nerve-immunity interaction in the treatment of depression: an integrated investigation of the miRNA-mRNA regulatory networks.", "doi": "10.18632/aging.204030", "pmid": "35468096", "authors": ["Zixuan Wu", "Zhixiang Cai", "Hongshuo Shi", "Xuyan Huang", "Minjie Cai", "Kai Yuan", "Peidong Huang", "Guoqi Shi", "Tao Yan", "Zhichao Li"], "journal": "Aging", "year": 2022, "abstract": "BACKGROUND: Major depressive disorder (MDD) is an emotional condition that interferes with sufferers' work and daily life. Numerous studies have found that miRNAs play a significant role in the development of MDD and can be utilized as a biomarker for its diagnosis and therapy. However, there have been few studies on nerve-immunity interaction treatment for the brains of MMD patients.\nMETHODS: The work is performed on microarray data. We analyzed the differences of miRNAs (GSE58105, GSE81152, GSE152267, and GSE182194) and mRNA (GSE19738, GSE32280, GSE44593, GSE53987, and GSE98793) in MDD and healthy samples from GEO datasets. FunRich was used to predict the transcription factors and target genes of the miRNAs, and TF and GO enrichment analyses were performed. Then, by comparing the differential expression of the anticipated target genes and five mRNAs, intersecting mRNAs were discovered. The intersecting genes were submitted to GO and KEGG analyses to determine their functions. These intersecting potential genes and pathways that linked to MDD in neurological and immunological aspects have been identified for future investigation.\nRESULTS: We discovered five hub genes: KCND2, MYT1L, GJA1, CHL1, and SNAP25, which were all up-regulated genes. However, in MMD, the equivalent miRNAs, hsa-miR-206 and hsa-miR-338-3p, were both down-regulated. These miRNAs can activate or inhibit the T cell receptor signal pathway, JAK-STAT and other signal pathways, govern immune-inflammatory response, neuronal remodeling, and mediate the onset and development of MMD Conclusions: The results of a thorough bioinformatics investigation of miRNAs and mRNAs in MDD showed that miR-338-3P and miR-206 might be effective biomarkers and possible therapeutic targets for the treatment of MDD via nerve-immunity interaction.", "claims": [{"id": "claim-method", "statement": "Genes acquired by the Limma software were determined to be significantly differentially expressed miRNAs using the corrected miRNA chip dataset and log2 (fold change) >2 or log2 (fold change) <−2 as screening thresholds (DE-miRNAs).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35468096", "locator": "sections[3] \"Data processing of DE-miRNAs\" paragraph 2", "quote": "Genes acquired by the Limma software were determined to be significantly differentially expressed miRNAs using the corrected miRNA chip dataset and log2 (fold change) >2 or log2 (fold change) <−2 as screening thresholds (DE-miRNAs)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets generated during and/or analyzed during the current study are available in the [GEO] repository, https://www.ncbi.nlm.nih.gov/geo/. The datasets generated during and/or analyzed during the current study are available from Supplementary.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35468096", "locator": "sections[10] \"Data availability statement\" paragraph 2", "quote": "The datasets generated during and/or analyzed during the current study are available in the [GEO] repository, https://www.ncbi.nlm.nih.gov/geo/. The datasets generated during and/or analyzed during the current study are available from Supplementary."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The integrated analysis identified 34 DE-miRNAs and 386 DE-mRNAs in MDD and healthy-control datasets.", "kind": "quantitative", "target": {"value": 0.05, "unit": "p-value", "tolerance": null, "source": "The combined dataset of 42 healthy people and 88 MMD patients revealed 34 DE-miRNAs (20 up-regulated and 14 down-regulated), following the screening with P < 0.05 and log2 (fold change) ≥2."}, "evidence": [{"asset": "source:pmid:35468096", "locator": "sections[14] \"Identification of DE-miRNAs and DE-mRNAs\" paragraph 2", "quote": "The combined dataset of 42 healthy people and 88 MMD patients revealed 34 DE-miRNAs (20 up-regulated and 14 down-regulated), following the screening with P < 0.05 and log2 (fold change) ≥2."}, {"asset": "source:pmid:35468096", "locator": "sections[14] \"Identification of DE-miRNAs and DE-mRNAs\" paragraph 2", "quote": "A total of 386 DE-mRNAs were identified after screening with P < 0.05 and log2(fold change) ≥2 (181up-regulated and 205 down-regulated)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The integrated analysis identified 34 DE-miRNAs and 386 DE-mRNAs in MDD and healthy-control datasets.", "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:35468096"], "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:GSE152267"], "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:GSE152267"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35468096", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.18632/aging.204030", "sha256": "sha256:5a8cff7eb862c5dca49235559b6a0dbd40eec61854471c385f5aa9a8c0b87b43", "bytes": 40010, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.18632/aging.204030", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9085226", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE152267", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE152267", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE152267", "version": null, "note": "The datasets generated during and/or analyzed during the current study are available in the [GEO] repository, https://www.ncbi.nlm.nih.gov/geo/. 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No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:35468096", "data:geo:GSE152267"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE152267"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:43:27Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 11100, "completion_tokens": 1788, "cached_tokens": 264}}, "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:35468096", "type": "paper", "label": "pmid:35468096"}, {"id": "source:pmid:35468096", "type": "manuscript", "label": "PMID 35468096 full text"}, {"id": "data:geo:GSE152267", "type": "dataset", "label": "GEO GSE152267"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:35468096", "type": "paper", "label": "pmid:35468096"}, {"id": "source:pmid:35468096", "type": "manuscript", "label": "PMID 35468096 full text"}, {"id": "data:geo:GSE152267", "type": "dataset", "label": "GEO GSE152267"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-35468096", "type": "extraction", "used": ["source:pmid:35468096"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE152267", "type": "accession_resolution", "used": ["data:geo:GSE152267"], "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:35468096", "parent_hash": "sha256:6c7002a9509952721317cd538fbc5c8e49292220e6c8c98f0d0f18eb18cb6912", "fork_of": null, "generation": 4}, "gaps": ["asset:data:geo:GSE152267 licence not read", "asset:data:geo:GSE152267 not downloaded", "asset:data:geo:GSE182194 licence not read", "asset:data:geo:GSE182194 not downloaded", "asset:data:geo:GSE19738 licence not read", "asset:data:geo:GSE19738 not downloaded", "asset:data:geo:GSE32280 licence not read", "asset:data:geo:GSE32280 not downloaded", "asset:data:geo:GSE44593 licence not read", "asset:data:geo:GSE44593 not downloaded", "asset:data:geo:GSE53987 licence not read", "asset:data:geo:GSE53987 not downloaded", "asset:data:geo:GSE58105 licence not read", "asset:data:geo:GSE58105 not downloaded", "asset:data:geo:GSE81152 licence not read", "asset:data:geo:GSE81152 not downloaded", "asset:data:geo:GSE98793 licence not read", "asset:data:geo:GSE98793 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["patients. METHODS: The work is performed on microarray data. We analyzed the differences of miRNAs"], "order_basis": "paper_text_order:552", "id": "assay:1"}, {"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Genes acquired by the Limma software were determined to be significantly differentially expressed miRNAs using the corrected miRNA chip dataset and log2 (fold change) >2 or log2 (fold change) <−2 as screening thresholds (DE-miRNAs)."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}