Evidence map›Paper›PMID 40967225›Full record

ArticleCell genomics2025

Single-nucleus transcriptome atlas of orbitofrontal cortex in ALS with a deep learning-based decoding of alternative polyadenylation mechanisms.

Paul M McKeever, Aiden M Sababi, Raghav Sharma, Zhiyu Xu, Shangxi Xiao, Philip McGoldrick, Troy Ketela, Christine Sato, Danielle Moreno, Naomi Visanji and 7 more

Abstract read
In one paragraph

Article in Cell genomics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–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

6 citing papers in PubMed.

  1. Article
  2. Article
  3. Aberrant Splicing Signatures Underpin Oligodendrocyte Damage in ALS and Neuron Loss in FTD.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  4. Review
  5. Article
  6. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Paul M McKeeverTanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada.
Aiden M SababiDepartment of Molecular Genetics, University of Toronto, Toronto, ON, Canada; The Donnelly Centre, University of Toronto, Toronto, ON, Canada.
Raghav SharmaTanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
Zhiyu XuPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Shangxi XiaoTanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada.
Philip McGoldrickTanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada.
Troy KetelaPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Christine SatoTanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada.
Danielle MorenoTanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada.
Naomi VisanjiTanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada.
Gabor G KovacsTanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
Julia KeithLaboratory Medicine and Molecular Diagnostics, Division of Anatomical Pathology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
Lorne ZinmanDivision of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
Ekaterina RogaevaTanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada.
Hani GoodarziDepartment of Biophysics and Biochemistry, University of California, San Francisco, San Francisco, CA, USA; Arc Institute, Palo Alto, CA, USA.
Gary D BaderDepartment of Molecular Genetics, University of Toronto, Toronto, ON, Canada; The Donnelly Centre, University of Toronto, Toronto, ON, Canada; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; Lunenfeld-Tanenbaum Research Institute, Sinai Health System, University of Toronto, Toronto, ON, Canada; Department of Computer Science, University of Toronto, Toronto, ON, Canada. Electronic address: gary.bader@utoronto.ca.
Janice RobertsonTanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada. Electronic address: jan.robertson@utoronto.ca.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are fatal neurodegenerative diseases sharing clinical and pathological features. Both involve complex neuron-glia interactions, but cell-type-specific alterations remain poorly defined. We performed single-nucleus RNA sequencing of the frontal cortex from C9orf72-related ALS (with and without FTLD) and sporadic ALS (sALS). Neurons showed prominent changes in mitochondrial function, protein homeostasis, and chromatin remodeling. Comparison with independent datasets from other cortical regions revealed consistent pathway alterations, including upregulation of STMN2 and NEFL across brain regions and subtypes. We further examined dysregulation of alternative polyadenylation (APA), an understudied post-transcriptional mechanism, uncovering cell-type-specific APA patterns. To investigate its regulation, we developed the alternative polyadenylation network (APA-Net), a multi-modal deep learning model integrating transcript sequences and RNA-binding protein (RBP) expression profiles to predict APA. This atlas advances our understanding of ALS/FTLD molecular pathology and provides a valuable resource for future mechanistic studies.

Indexed as

Amyotrophic Lateral SclerosisDeep LearningPolyadenylationPrefrontal CortexTranscriptomeAgedC9orf72 ProteinFemaleFrontotemporal Lobar DegenerationHumansMaleMiddle AgedNeuronsC9orf72 ProteinC9orf72 protein, humanalternative polyadenylationamyotrophic lateral sclerosisartificial intelligencedeep learningfrontal cortexfrontotemporal lobar degenerationRNA-binding proteinssingle-cellsingle-nucleustranscriptomics

Identifiers

PMID40967225
PMCPMC12802741

What Socratic holds

Textmetadata
LicenceCC BY-NC
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.