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Record W3043048574 · doi:10.1016/j.celrep.2020.107908

Meta-Analysis of the Alzheimer’s Disease Human Brain Transcriptome and Functional Dissection in Mouse Models

2020· review· en· W3043048574 on OpenAlexaff
Ying‐Wooi Wan, Rami Al‐Ouran, Carl Grant Mangleburg, Thanneer M. Perumal, Tom V. Lee, Katherine Allison, Vivek Swarup, Cory C. Funk, Chris Gaiteri, Mariet Allen, Minghui Wang, Sarah M. Neuner, Catherine C. Kaczorowski, Vivek M. Philip, Gareth R. Howell, Heidi Martini‐Stoica, Hui Zheng, Hongkang Mei, Xiaoyan Zhong, Jungwoo Wren Kim, Valina L. Dawson, Ted M. Dawson, Ping‐Chieh Pao, Li‐Huei Tsai, Jean‐Vianney Haure‐Mirande, Michelle E. Ehrlich, Paramita Chakrabarty, Yona Levites, Xue Wang, Eric B. Dammer, Gyan Srivastava, Sumit Mukherjee, Solveig K. Sieberts, Larsson Omberg, Kristen K. Dang, James A. Eddy, Phil Snyder, Yooree Chae, Sandeep Amberkar, Wenbin Wei, Christoph Preuß, Ayla Ergün, Phillip J. Ebert, David Airey, Sara Mostafavi, Lei Yu, Hans‐Ulrich Klein, Gregory W. Carter, David Collier, Todd E. Golde, Allan I. Levey, David A. Bennett, Karol Estrada, T. Matthew Townsend, Bin Zhang, Eric E. Schadt, Philip L. De Jager, Nathan D. Price, Nilüfer Ertekin‐Taner, Zhandong Liu, Joshua M. Shulman, Lara M. Mangravite, Benjamin A. Logsdon

Bibliographic record

VenueCell Reports · 2020
Typereview
Languageen
FieldMedicine
TopicAlzheimer's disease research and treatments
Canadian institutionsUniversity of British Columbia
FundersDivision of Mathematical SciencesNational Institute of Neurological Disorders and StrokeNational Institute on AgingAlzheimer's Disease Research Center, University of PittsburghSchool of Medicine, Johns Hopkins UniversityNational Institutes of HealthIcahn School of Medicine at Mount SinaiHuffington FoundationTranslational Genomics Research InstituteJohns Hopkins HospitalCurePSPVeterans Administration Medical CenterJPB FoundationTexas Children's HospitalMayo ClinicCancer Prevention and Research Institute of TexasCullen FoundationRush UniversityIllinois Department of Public HealthMichael J. Fox Foundation for Parkinson's ResearchEmory UniversityHouston EndowmentAdrienne Helis Malvin Medical Research FoundationMayo Foundation for Medical Education and ResearchJohns Hopkins UniversityArizona Biomedical Research CommissionBoler Family FoundationArizona Department of Health ServicesBurroughs Wellcome FundNational Science Foundation
KeywordsTranscriptomeDiseaseNeuroscienceComputational biologyHuman brainBiologyBioinformaticsMedicineGeneGeneticsGene expressionInternal medicine

Abstract

fetched live from OpenAlex

We present a consensus atlas of the human brain transcriptome in Alzheimer's disease (AD), based on meta-analysis of differential gene expression in 2,114 postmortem samples. We discover 30 brain coexpression modules from seven regions as the major source of AD transcriptional perturbations. We next examine overlap with 251 brain differentially expressed gene sets from mouse models of AD and other neurodegenerative disorders. Human-mouse overlaps highlight responses to amyloid versus tau pathology and reveal age- and sex-dependent expression signatures for disease progression. Human coexpression modules enriched for neuronal and/or microglial genes broadly overlap with mouse models of AD, Huntington's disease, amyotrophic lateral sclerosis, and aging. Other human coexpression modules, including those implicated in proteostasis, are not activated in AD models but rather following other, unexpected genetic manipulations. Our results comprise a cross-species resource, highlighting transcriptional networks altered by human brain pathophysiology and identifying correspondences with mouse models for AD preclinical studies.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.005
metaresearch head score (Gemma)0.005
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Meta-analysis · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.005
Threshold uncertainty score0.025

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0050.005
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0030.005
Bibliometrics0.0040.004
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.208
GPT teacher head0.373
Teacher spread0.164 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designMeta-analysis
Domainnot available
GenreReview

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations330
Published2020
Admission routes1
Has abstractyes

Explore more

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