Evidence map›Paper›PMID 34953465›Full record

ArticleBriefings in bioinformatics2022

An integrated brain-specific network identifies genes associated with neuropathologic and clinical traits of Alzheimer's disease.

Cui-Xiang Lin, Hong-Dong Li, Chao Deng, Weisheng Liu, Shannon Erhardt, Fang-Xiang Wu, Xing-Ming Zhao, Yuanfang Guan, Jun Wang, Daifeng Wang and 2 more

Abstract read
In one paragraph

Article in Briefings in bioinformatics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Cui-Xiang LinSchool of Computer Science and Engineering, Central South University, Changsha, Hunan 410083, P. R. China.
Hong-Dong LiSchool of Computer Science and Engineering, Central South University, Changsha, Hunan 410083, P. R. China.
Chao DengHunan Provincial Key Lab on Bioinformatics, School of Computer Science and Engineering, Central South University, Changsha, Hunan 410083, P. R. China.
Weisheng LiuSchool of Computer Science and Engineering, Central South University, Changsha, Hunan 410083, P. R. China.
Shannon ErhardtDepartment of Pediatrics, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
Fang-Xiang WuDivision of Biomedical Engineering, University of Saskatchewan, Saskatoon, SKS7N5A9, Canada.
Xing-Ming ZhaoInstitute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China.
Yuanfang GuanDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, United States.
Jun WangDepartment of Pediatrics, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
Daifeng WangDepartment of Biostatistics and Medical Informatics and Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Bin HuInstitute of Engineering Medicine, Beijing Institute of Technology, Beijing, China.
Jianxin WangSchool of Computer Science and Engineering, Central South University, Changsha, Hunan 410083, P. R. China.

Funding

Vascular Structure and Function in Cognitive AgingP01AG003949 · NIA · YESHIVA UNIVERSITY · PI Richard B. LIPTON · 1985 to 2026
$73.9M
SUPPLEMENT TO ALZHEIMERS DISEASE PATIENT REGISTRYU01AG006786 · NIA · MAYO CLINIC ROCHESTER · PI GRAFF-RADFORD, JONATHAN, JACK, CLIFFORD R. · 1986 to 2023
$49.6M
THE PGRN/TDP-43 AXIS IN ALZHEIMER?S DISEASE AND NEURODEGENERATIONP50AG016574 · NIA · MAYO CLINIC ROCHESTER · PI PETERSEN, RONALD C · 1999 to 2018
$36.9M
Research Education ComponentP30AG019610 · NIA · SUN HEALTH RESEARCH INSTITUTE · PI REIMAN, ERIC MICHAEL · 2001 to 2020
$32.5M
Integrating the exposome and methylome to inform brain molecular changes in ADRD across established diverse cohorts.U01AG046139 · NIA · UNIVERSITY OF FLORIDA · PI ERTEKIN-TANER, NILUFER, FUNK, CORY · 2013 to 2022
$24.6M
TRANSGENIC MODELING OF TAUOPATHYP01AG017216 · NIA · MAYO CLINIC JACKSONVILLE · PI DICKSON, DENNIS WILLIAM · 1999 to 2011
$12.0M
PREDICTORS OF THE RATE OF COGNITIVE DECLINE IN ELDERLY SUBJECTSP50AG025711 · NIA · UNIVERSITY OF SOUTH FLORIDA · PI POTTER, HUNTINGTON · 2005 to 2010
$8.2M
National Brain and Tissue Resource for Parkinson's Disease and Related DisordersU24NS072026 · NINDS · BANNER SUN HEALTH RESEARCH INSTITUTE · PI BEACH, THOMAS G · 2011 to 2015
$7.8M
PLASMA A BETA AS A SURROGATE GENETIC MARKER FOR LOADR01AG018023 · NIA · MAYO CLINIC JACKSONVILLE · PI YOUNKIN, STEVEN G · 2001 to 2012
$3.3M
Gene discovery in PSP by transcriptome, neuropathology and sequence analysisR01NS080820 · NINDS · MAYO CLINIC JACKSONVILLE · PI ERTEKIN-TANER, NILUFER · 2013 to 2017
$1.8M
Genome wide association study of gene expression levels in Alzheimer's diseaseR01AG032990 · NIA · MAYO CLINIC JACKSONVILLE · PI ERTEKIN-TANER, NILUFER · 2009 to 2011
$932k
NIA NIH HHS P01 AG003949NIA NIH HHS P01 AG017216NIA NIH HHS P30 AG019610NIA NIH HHS P50 AG016574NIA NIH HHS P50 AG025711NIA NIH HHS R01 AG018023NIA NIH HHS R01 AG032990NIA NIH HHS U01 AG006786NIA NIH HHS U01 AG046139NINDS NIH HHS R01 NS080820NINDS NIH HHS U24 NS072026
6 · The paper itself

Abstract

Alzheimer's disease (AD) has a strong genetic predisposition. However, its risk genes remain incompletely identified. We developed an Alzheimer's brain gene network-based approach to predict AD-associated genes by leveraging the functional pattern of known AD-associated genes. Our constructed network outperformed existing networks in predicting AD genes. We then systematically validated the predictions using independent genetic, transcriptomic, proteomic data, neuropathological and clinical data. First, top-ranked genes were enriched in AD-associated pathways. Second, using external gene expression data from the Mount Sinai Brain Bank study, we found that the top-ranked genes were significantly associated with neuropathological and clinical traits, including the Consortium to Establish a Registry for Alzheimer's Disease score, Braak stage score and clinical dementia rating. The analysis of Alzheimer's brain single-cell RNA-seq data revealed cell-type-specific association of predicted genes with early pathology of AD. Third, by interrogating proteomic data in the Religious Orders Study and Memory and Aging Project and Baltimore Longitudinal Study of Aging studies, we observed a significant association of protein expression level with cognitive function and AD clinical severity. The network, method and predictions could become a valuable resource to advance the identification of risk genes for AD.

Indexed as

Gene Regulatory NetworksGenetic Predisposition to DiseaseAgingAlzheimer DiseaseBrainGene Expression ProfilingHumansLongitudinal StudiesMemoryProteomicsRNA-SeqTranscriptomebrain gene networkdisease gene predictionmulti-omics

Identifiers

PMID34953465
PMCPMC8769916

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.