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pmid:35875800

Hub Genes, Diagnostic Model, and Predicted Drugs Related to Iron Metabolism in Alzheimer's Disease.

Xuefeng Gu · Donglin Lai · Shuang Liu · Kaijie Chen · Peng Zhang · Bing Chen · Gang Huang · Xiaoqin Cheng · Changlian Lu

Frontiers in aging neuroscience · 2022 doi:10.3389/fnagi.2022.949083

Paper

complete

Experiment

complete

Data

partial

Analysis

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Execution

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title
Hub Genes, Diagnostic Model, and Predicted Drugs Related to Iron Metabolism in Alzheimer's Disease.
doi
10.3389/fnagi.2022.949083
pmid
35875800
authors array · 9 items
[0]
Xuefeng Gu
[1]
Donglin Lai
[2]
Shuang Liu
[3]
Kaijie Chen
[4]
Peng Zhang
[5]
Bing Chen
[6]
Gang Huang
[7]
Xiaoqin Cheng
[8]
Changlian Lu
journal
Frontiers in aging neuroscience
year
2022
abstract
Alzheimer's disease (AD), the most common neurodegenerative disease, remains unclear in terms of its underlying causative genes and effective therapeutic approaches. Meanwhile, abnormalities in iron metabolism have been demonstrated in patients and mouse models with AD. Therefore, this study sought to find hub genes based on iron metabolism that can influence the diagnosis and treatment of AD. First, gene expression profiles were downloaded from the GEO database, including non-demented (ND) controls and AD samples. Fourteen iron metabolism-related gene sets were downloaded from the MSigDB database, yielding 520 iron metabolism-related genes. The final nine hub genes associated with iron metabolism and AD were obtained by differential analysis and WGCNA in brain tissue samples from GSE132903. GO analysis revealed that these genes were mainly involved in two major biological processes, autophagy and iron metabolism. Through stepwise regression and logistic regression analyses, we selected four of these genes to construct a diagnostic model of AD. The model was validated in blood samples from GSE63061 and GSE85426, and the AUC values showed that the model had a relatively good diagnostic performance. In addition, the immune cell infiltration of the samples and the correlation of different immune factors with these hub genes were further explored. The results suggested that these genes may also play an important role in immunity to AD. Finally, eight drugs targeting these nine hub genes were retrieved from the DrugBank database, some of which were shown to be useful for the treatment of AD or other concomitant conditions, such as insomnia and agitation. In conclusion, this model is expected to guide the diagnosis of patients with AD by detecting the expression of several genes in the blood. These hub genes may also assist in understanding the development and drug treatment of AD.
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Differential expression analysis of AD and ND samples was performed using the “limma” package in R software.
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sections[4] "Differential Expression Analysis" paragraph 2
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Differential expression analysis of AD and ND samples was performed using the “limma” package in R software.
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sections[21] "Data Availability Statement" paragraph 2
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The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.
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[264]
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[265]
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[266]
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[267]
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[268]
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[269]
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[270]
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[271]
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[272]
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[273]
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[274]
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[275]
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[276]
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[277]
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[278]
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[279]
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[280]
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[281]
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[282]
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[283]
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[284]
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[285]
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[286]
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[287]
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[288]
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[289]
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[290]
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[291]
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[292]
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[293]
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[294]
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[295]
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[296]
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[297]
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[298]
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[299]
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[300]
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[301]
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[302]
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[303]
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[304]
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[305]
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[306]
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[307]
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[308]
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[309]
GSM1539718
[310]
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[311]
GSM1539720
[312]
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[313]
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[314]
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[315]
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[316]
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[317]
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[318]
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[319]
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[320]
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[321]
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[322]
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[323]
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[324]
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[325]
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[326]
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[328]
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[329]
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[330]
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[331]
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[332]
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[333]
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[334]
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[335]
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[336]
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[337]
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[338]
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[339]
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[340]
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[341]
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[342]
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[343]
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[344]
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[345]
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[346]
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[347]
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[348]
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[349]
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[350]
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[351]
GSM1539760
[352]
GSM1539761
[353]
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[354]
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[355]
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[356]
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[357]
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[359]
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[360]
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[361]
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[362]
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[363]
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[364]
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[365]
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[366]
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[367]
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[368]
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[369]
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[370]
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[371]
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[372]
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[373]
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[374]
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[375]
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[376]
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[377]
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[378]
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[379]
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[380]
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[381]
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[382]
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[383]
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[384]
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[385]
GSM1539794
[386]
GSM1539795
[387]
GSM1539796
sample_count
388
group_sizes
null
group_sizes_basis
null
platform
10558
taxon
Homo sapiens
title
Alzheimer, Mild Cognitive impairment and control samples from AddneuroMed Cohort (batch 2)
resolution_checked_at
2026-11-01T15:39:55Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[3] object · 15 fields
id
data:geo:GSE85426
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=GSE85426
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
GSE85426
version
null
note
The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.
access_statement_kind
data_availability_statement
sample_accessions array · 180 items
[0]
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[1]
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[6]
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[7]
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[8]
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[9]
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[10]
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[11]
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[12]
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[13]
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[14]
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[15]
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[16]
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[17]
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[18]
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[19]
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[20]
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[21]
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[22]
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[23]
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[24]
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[25]
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[26]
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[27]
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[28]
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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]
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[34]
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[35]
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[36]
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[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]
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[43]
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[44]
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[45]
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[46]
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[47]
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[48]
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[49]
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[50]
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[51]
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[52]
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[53]
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[54]
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[55]
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[56]
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[57]
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[58]
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[59]
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[60]
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[62]
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[63]
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[64]
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[65]
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[66]
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[67]
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[68]
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[69]
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[70]
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[71]
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[72]
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[73]
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[74]
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[75]
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[76]
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[77]
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[78]
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[79]
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[80]
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[81]
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[82]
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[83]
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[84]
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[85]
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[86]
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[87]
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[88]
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[89]
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[90]
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[91]
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[92]
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[93]
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[97]
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[98]
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[100]
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[102]
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[103]
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[107]
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[109]
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[110]
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[111]
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[112]
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[113]
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[117]
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[120]
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[121]
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[122]
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[123]
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[125]
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[127]
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[128]
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[129]
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[130]
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[131]
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[132]
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[133]
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[134]
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[135]
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[136]
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[137]
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[138]
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[139]
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[140]
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[141]
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[142]
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[143]
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[151]
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[152]
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[154]
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[162]
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[163]
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[178]
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[179]
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sample_count
180
group_sizes
null
group_sizes_basis
null
platform
14550
taxon
Homo sapiens
title
Peripheral blood gene expression as a biomarker for early detection of Alzheimer’s disease
resolution_checked_at
2026-11-01T18:06:44Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
gaps array · 6 items
[0]
asset:data:geo:GSE132903 not downloaded
[1]
asset:data:geo:GSE132903 licence not read
[2]
asset:data:geo:GSE63061 not downloaded
[3]
asset:data:geo:GSE63061 licence not read
[4]
asset:data:geo:GSE85426 not downloaded
[5]
asset:data:geo:GSE85426 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
Differential expression analysis of AD and ND samples was performed using the “limma” package in R software.
[1] object · 10 fields
id
method-2
family
regression_modelling
specific
logistic
label
Regression modelling
dsl_operations array · 1 item
[0]
glm_logit_fit
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
predictors_and_outcome
evidence object · 3 fields
score
0.7
band
medium
quote
logistic regression
targets array · 0 items
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
method object · 5 fields
tier
R1
expressible
true
required_operations array · 3 items
[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
missing_operations array · 0 items
basis
The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: limma_voom.
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
reachable
true
accessions array · 3 items
[0]
GSE132903
[1]
GSE63061
[2]
GSE85426
resolved_accessions array · 3 items
[0]
GSE132903
[1]
GSE63061
[2]
GSE85426
statements array · 1 item
[0]
The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.
basis
The paper names GSE132903, GSE63061, GSE85426 in NCBI Gene Expression Omnibus (GEO) 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
[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
assets array · 2 items
[0]
source:pmid:35875800
[1]
data:geo:GSE132903
steps array · 1 item
[0]
run_analysis
must_build object · 5 fields
dsl_operations array · 0 items
converters array · 0 items
readers array · 0 items
capabilities array · 0 items
data_gaps array · 1 item
[0]
data:geo:GSE132903
gaps array · 0 items
review object · 5 fields
state
partial
machine_critique object · 5 fields
kind
extraction_review
reader object · 5 fields
model
MiniMax-M3.1-Flash
provider
minimax
provider_family
minimax
read_at
2026-11-01T17:56:50Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
calls
5
usage object · 3 fields
prompt_tokens
10434
completion_tokens
1324
cached_tokens
128
stages array · 1 item
[0] object · 4 fields
id
extraction
state
complete
reader
MiniMax-M3.1-Flash
provider
minimax
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[0]
review.independent_reader
[1]
review.machine_critique
[2]
review.human_critique
execution object · 5 fields
state
absent
status
not_run
mode
null
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gaps array · 1 item
[0]
execution.not_run
provenance object · 7 fields
entities array · 3 items
[0] object · 3 fields
id
pmid:35875800
type
paper
label
pmid:35875800
[1] object · 3 fields
id
source:pmid:35875800
type
manuscript
label
PMID 35875800 full text
[2] object · 3 fields
id
data:geo:GSE132903
type
dataset
label
GEO GSE132903
activities array · 3 items
[0] object · 4 fields
id
activity-reading-sci-2026-11-01
type
classification
used array · 3 items
[0] object · 3 fields
id
pmid:35875800
type
paper
label
pmid:35875800
[1] object · 3 fields
id
source:pmid:35875800
type
manuscript
label
PMID 35875800 full text
[2] object · 3 fields
id
data:geo:GSE132903
type
dataset
label
GEO GSE132903
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-35875800
type
extraction
used array · 1 item
[0]
source:pmid:35875800
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE132903
type
accession_resolution
used array · 1 item
[0]
data:geo:GSE132903
agent
agent:corpus-assay-engine
agents array · 2 items
[0] object · 3 fields
id
agent:corpus-assay-engine
type
software
label
Corpus assay engine
[1] object · 3 fields
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 object · 4 fields
parent_id
pmid:35875800
parent_hash
sha256:c7fc8c7022ce5ccfe0c4e62d1f5214c2f009dce2c2730494b64be3959280c962
fork_of
null
gaps array · 10 items
[0]
asset:data:geo:GSE132903 licence not read
[1]
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[2]
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[3]
asset:data:geo:GSE63061 not downloaded
[4]
asset:data:geo:GSE85426 licence not read
[5]
asset:data:geo:GSE85426 not downloaded
[6]
execution.not_run
[7]
review.human_critique
[8]
review.independent_reader
[9]
review.machine_critique
assays array · 3 items
[0] object · 11 fields
role
data_generation
definition_id
animal_model
definition_version
99e1195c7d6f
required_operations array · 0 items
support_state
partial
source_hashes object · 1 field
assay_lexicon
99e1195c7d6f
confidence
0.69
evidence array · 1 item
[0]
olism have been demonstrated in patients and mouse models with AD. Therefore, this study sought
order_basis
paper_text_order:304
id
assay:1
[1] object · 11 fields
role
data_generation
definition_id
clinical_cohort
definition_version
99e1195c7d6f
required_operations array · 0 items
support_state
partial
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assay_lexicon
99e1195c7d6f
confidence
0.99
evidence array · 3 items
[0]
model is expected to guide the diagnosis of patients with AD by detecting the expression of several ge
[1]
stic model of AD. The model was validated in blood samples from GSE63061 and GSE85426, and the AUC values sh
[2]
sion of hub genes in the AD and ND groups of blood samples from GSE63061. (A) ATP6V1D. (B) ATP6V1G2. (C) ATP
order_basis
paper_text_order:1143
id
assay:2
[2] object · 11 fields
role
analysis
definition_id
differential_expression
definition_version
f2132e96ae6c7a4e
required_operations array · 3 items
[0]
normalise_counts
[1]
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[2]
fdr_bh
support_state
supported
source_hashes object · 1 field
dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
[0]
Differential expression analysis of AD and ND samples was performed using the “limma” package in R software.
order_basis
consumes_earlier_output
id
assay:3
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35875800", "kind": "science-record", "revision": 5, "content_hash": "sha256:1aead7748008a0bdaa9ec3ea6f262390578df6873ccfd3ffea44d0216794f1e2", "created_at": "2026-11-01T18:14:58Z", "updated_at": "2026-11-01T22:49:38Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Hub Genes, Diagnostic Model, and Predicted Drugs Related to Iron Metabolism in Alzheimer's Disease.", "doi": "10.3389/fnagi.2022.949083", "pmid": "35875800", "authors": ["Xuefeng Gu", "Donglin Lai", "Shuang Liu", "Kaijie Chen", "Peng Zhang", "Bing Chen", "Gang Huang", "Xiaoqin Cheng", "Changlian Lu"], "journal": "Frontiers in aging neuroscience", "year": 2022, "abstract": "Alzheimer's disease (AD), the most common neurodegenerative disease, remains unclear in terms of its underlying causative genes and effective therapeutic approaches. Meanwhile, abnormalities in iron metabolism have been demonstrated in patients and mouse models with AD. Therefore, this study sought to find hub genes based on iron metabolism that can influence the diagnosis and treatment of AD. First, gene expression profiles were downloaded from the GEO database, including non-demented (ND) controls and AD samples. Fourteen iron metabolism-related gene sets were downloaded from the MSigDB database, yielding 520 iron metabolism-related genes. The final nine hub genes associated with iron metabolism and AD were obtained by differential analysis and WGCNA in brain tissue samples from GSE132903. GO analysis revealed that these genes were mainly involved in two major biological processes, autophagy and iron metabolism. Through stepwise regression and logistic regression analyses, we selected four of these genes to construct a diagnostic model of AD. The model was validated in blood samples from GSE63061 and GSE85426, and the AUC values showed that the model had a relatively good diagnostic performance. In addition, the immune cell infiltration of the samples and the correlation of different immune factors with these hub genes were further explored. The results suggested that these genes may also play an important role in immunity to AD. Finally, eight drugs targeting these nine hub genes were retrieved from the DrugBank database, some of which were shown to be useful for the treatment of AD or other concomitant conditions, such as insomnia and agitation. In conclusion, this model is expected to guide the diagnosis of patients with AD by detecting the expression of several genes in the blood. These hub genes may also assist in understanding the development and drug treatment of AD.", "claims": [{"id": "claim-method", "statement": "Differential expression analysis of AD and ND samples was performed using the “limma” package in R software.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35875800", "locator": "sections[4] \"Differential Expression Analysis\" paragraph 2", "quote": "Differential expression analysis of AD and ND samples was performed using the “limma” package in R software."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35875800", "locator": "sections[21] \"Data Availability Statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors."}], "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:35875800"], "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:GSE132903"], "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:GSE132903"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35875800", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fnagi.2022.949083", "sha256": 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contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2266610", "GSM2266611", "GSM2266612", "GSM2266613", "GSM2266614", "GSM2266615", "GSM2266616", "GSM2266617", "GSM2266618", "GSM2266619", "GSM2266620", "GSM2266621", "GSM2266622", "GSM2266623", "GSM2266624", "GSM2266625", "GSM2266626", "GSM2266627", "GSM2266628", "GSM2266629", "GSM2266630", "GSM2266631", "GSM2266632", "GSM2266633", "GSM2266634", "GSM2266635", "GSM2266636", "GSM2266637", "GSM2266638", "GSM2266639", "GSM2266640", "GSM2266641", "GSM2266642", "GSM2266643", "GSM2266644", "GSM2266645", "GSM2266646", "GSM2266647", "GSM2266648", "GSM2266649", "GSM2266650", "GSM2266651", "GSM2266652", "GSM2266653", "GSM2266654", "GSM2266655", "GSM2266656", "GSM2266657", "GSM2266658", "GSM2266659", "GSM2266660", "GSM2266661", "GSM2266662", "GSM2266663", 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