Evidence map›Paper›PMID 38076956›Full record

ArticlemedRxiv : the preprint server for health sciences2023

Long-read RNA-seq atlas of novel microglia isoforms elucidates disease-associated genetic regulation of splicing.

Jack Humphrey, Erica Brophy, Roman Kosoy, Biao Zeng, Elena Coccia, Daniele Mattei, Ashvin Ravi, Anastasia G Efthymiou, Elisa Navarro, Benjamin Z Muller and 24 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed, 5 citations in OpenAlex.

  1. Circulating tumor DNA-based detection of molecular residual disease in isocitrate dehydrogenase-mutant cholangiocarcinoma for biomarker-guided therapy.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

34 authors at 5 institutions in 2 countries.

Jack HumphreyDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0002-6274-6620
Erica BrophyDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Roman KosoyDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Biao ZengDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Elena CocciaDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0002-9849-2423
Daniele MatteiDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0001-6221-9321
Ashvin RaviDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Anastasia G EfthymiouDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0002-1769-5078
Elisa NavarroDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0002-4056-7146
Benjamin Z MullerDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0009-0004-9712-6378
Gijsje Jlj SnijdersNash Family Department of Neuroscience & Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0002-2694-1234
Amanda AllanDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0002-7627-4126
Alexandra MünchDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0002-9609-3277
Reta Birhanu KitataBiological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.ORCID 0000-0002-8973-7679
Steven P KleopoulosDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Stathis ArgyriouDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0009-0008-0713-6599
Zhiping ShaoDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Nancy FrancoeurDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0003-1798-3587
Chia-Feng TsaiBiological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.
Marina A GritsenkoBiological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.
Matthew E MonroeBiological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.ORCID 0000-0002-1210-7169
Vanessa L PaurusBiological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.
Karl K WeitzBiological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.
Tujin ShiBiological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.ORCID 0000-0002-5592-3588
Robert SebraDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Tao LiuBiological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.ORCID 0000-0001-9529-6550
Lot D de WitteNash Family Department of Neuroscience & Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Alison M GoateDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0002-0576-2472
David A BennettRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA.
Vahram HaroutunianNash Family Department of Neuroscience & Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Gabriel E HoffmanDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0002-0957-0224
John F FullardDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0001-9874-2907
Panos RoussosDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0002-4640-6239
Towfique RajDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0002-9355-5704
Allen Institute for Brain Science · USPacific Northwest National Laboratory · USIcahn School of Medicine at Mount Sinai · USRush University Medical Center · USUniversidad Complutense de Madrid · ES

Funding

Conduits: Mount Sinai Health System Translational Science HubUL1TR004419 · NCATS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Rosalind J Wright · 2022 to 2026
$46.4M
Research Education ComponentP30AG066514 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Margaret Sewell · 2020 to 2026
$31.0M
Rush Alzheimer's Disease Research CenterP30AG072975 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI Lisa L Barnes, Julie A. Schneider · 2021 to 2026
$24.7M
Understanding the molecular mechanisms that contribute to neuropsychiatric symptoms in Alzheimer DiseaseR01AG067025 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI FINKBEINER, STEVEN M, HAROUTUNIAN, VAHRAM · 2019 to 2023
$11.8M
Higher Order Chromatin and Genetic Risk for Alzheimer's DiseaseR01AG050986 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI ROUSSOS, PANAGIOTIS · 2015 to 2025
$11.2M
Understanding the protective and neuroinflammatory role of human brain immune cells in Alzheimer DiseaseR01AG065582 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI HAROUTUNIAN, VAHRAM, ROUSSOS, PANAGIOTIS · 2020 to 2024
$9.9M
The adaptive-innate immune interactome across multiple tissues in Alzheimer's diseaseR01AG082185 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI VAHRAM HAROUTUNIAN, Donghoon Lee · 2023 to 2026
$9.0M
Human Biomarkers CoreU54NS123743 · NINDS · STANFORD UNIVERSITY · PI GITLER, AARON D. · 2021 to 2025
$8.2M
Learning the Regulatory Code of Alzheimer's Disease GenomesU01AG068880 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI KNOWLES, DAVID ARTHUR, RAJ, TOWFIQUE · 2020 to 2024
$5.8M
Multiethnic genomic epigenomic and transcriptomic fine-mapping and functional validation analysis of schizophrenia and bipolar disorder risk lociR01MH125246 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI ROUSSOS, PANAGIOTIS · 2021 to 2025
$5.0M
Genomic approach to identification of microglial networks involved in Alzheimer’s disease riskU01AG058635 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI GOATE, ALISON M · 2018 to 2022
$4.8M
The role of peripheral myeloid cells in Alzheimers diseaseR01AG054005 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI RAJ, TOWFIQUE · 2017 to 2021
$4.1M
NCATS NIH HHS UL1 TR004419NIA NIH HHS P30 AG066514NIA NIH HHS P30 AG072975NIA NIH HHS R01 AG050986NIA NIH HHS R01 AG054005NIA NIH HHS R01 AG065582NIA NIH HHS R01 AG065926NIA NIH HHS R01 AG067025NIA NIH HHS R01 AG082185NIA NIH HHS R21 AG063130NIA NIH HHS R56 AG055824NIA NIH HHS RF1 AG065926NIA NIH HHS T32 AG049688NIA NIH HHS U01 AG058635NIA NIH HHS U01 AG068880NIH HHS S10 OD026880NIH HHS S10 OD030463NIMH NIH HHS R01 MH125246NINDS NIH HHS R01 NS116006NINDS NIH HHS U01 NS125580NINDS NIH HHS U54 NS123743
6 · The paper itself

Abstract

Microglia, the innate immune cells of the central nervous system, have been genetically implicated in multiple neurodegenerative diseases. We previously mapped the genetic regulation of gene expression and mRNA splicing in human microglia, identifying several loci where common genetic variants in microglia-specific regulatory elements explain disease risk loci identified by GWAS. However, identifying genetic effects on splicing has been challenging due to the use of short sequencing reads to identify causal isoforms. Here we present the isoform-centric microglia genomic atlas (isoMiGA) which leverages the power of long-read RNA-seq to identify 35,879 novel microglia isoforms. We show that the novel microglia isoforms are involved in stimulation response and brain region specificity. We then quantified the expression of both known and novel isoforms in a multi-ethnic meta-analysis of 555 human microglia short-read RNA-seq samples from 391 donors, the largest to date, and found associations with genetic risk loci in Alzheimer's disease and Parkinson's disease. We nominate several loci that may act through complex changes in isoform and splice site usage.

Identifiers

PMID38076956
PMCPMC10705658
OpenAlexW4389272917

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

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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 OpenQuestion graph.