Evidence map›Paper›PMID 35688811›Full record

ArticleNature communications2022

Orgo-Seq integrates single-cell and bulk transcriptomic data to identify cell type specific-driver genes associated with autism spectrum disorder.

Elaine T Lim, Yingleong Chan, Pepper Dawes, Xiaoge Guo, Serkan Erdin, Derek J C Tai, Songlei Liu, Julia M Reichert, Mannix J Burns, Ying Kai Chan and 10 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.9field-weighted citation impact, top 14% of its field
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

18 citing papers in PubMed, 23 citations in OpenAlex.

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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

20 authors at 4 institutions in 2 countries.

Elaine T LimProgram in Bioinformatics and Integrative Biology, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA. elaine.lim@umassmed.edu.ORCID 0000-0003-3651-0654
Yingleong ChanProgram in Bioinformatics and Integrative Biology, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.
Pepper DawesProgram in Bioinformatics and Integrative Biology, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.
Xiaoge GuoDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, 02115, USA.
Serkan ErdinPsychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA.ORCID 0000-0001-6587-2625
Derek J C TaiPsychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA.
Songlei LiuDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, 02115, USA.ORCID 0000-0001-8607-8260
Julia M ReichertProgram in Bioinformatics and Integrative Biology, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.
Mannix J BurnsProgram in Bioinformatics and Integrative Biology, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.ORCID 0000-0001-6091-3010
Ying Kai ChanDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, 02115, USA.
Jessica J ChiangDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, 02115, USA.
Katharina MeyerDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, 02115, USA.
Xiaochang ZhangDepartment of Human Genetics, The University of Chicago, Chicago, IL, 60637, USA.ORCID 0000-0001-5768-7470
Christopher A WalshProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, 02115, USA.ORCID 0000-0002-0156-2238
Bruce A YanknerDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, 02115, USA.
Soumya RaychaudhuriProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, 02115, USA.ORCID 0000-0002-1901-8265
Joel N HirschhornDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, 02115, USA.
James F GusellaDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, 02115, USA.
Michael E TalkowskiPsychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA.ORCID 0000-0003-2889-0992
George M ChurchDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, 02115, USA. gchurch@genetics.med.harvard.edu.ORCID 0000-0003-3535-2076
Harvard University · USBroad Institute · USUniversity of Massachusetts Chan Medical School · USUniversity of Chicago · US

Funding

Center for Genomically Engineered OrgansRM1HG008525 · NHGRI · HARVARD MEDICAL SCHOOL · PI CHURCH, GEORGE M · 2015 to 2019
$10.2M
Genetic Analysis and Manipulation Core (GAEC)P50HD105351 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI SCOTT Loren POMEROY, MUSTAFA SAHIN · 2021 to 2026
$9.4M
Identification of the genetic and transcriptomic networks of cognitive and neuropathological resilience to Alzheimer's Disease associated virusesU01AG061835 · NIA · ARIZONA STATE UNIVERSITY-TEMPE CAMPUS · PI READHEAD, BENJAMIN · 2018 to 2022
$6.5M
Exploring a Novel Paradigm of Schizophrenia and Bipolar DisorderR01MH113279 · NIMH · HARVARD MEDICAL SCHOOL · PI CHURCH, GEORGE M, YANKNER, BRUCE A · 2016 to 2020
$4.7M
Targeting REST in Alzheimer's DiseaseR01AG069042 · NIA · HARVARD MEDICAL SCHOOL · PI YANKNER, BRUCE A · 2021 to 2025
$4.5M
Orchestra: A high performance biomedical supercomputing collaborativeS10RR028832 · NCRR · HARVARD MEDICAL SCHOOL · PI DANUSER, GAUDENZ · 2010 to 2010
$3.7M
Molecular mechanisms and genetic drivers of reciprocal genomic disordersR01HD096326 · NICHD · MASSACHUSETTS GENERAL HOSPITAL · PI TALKOWSKI, MICHAEL E · 2018 to 2022
$3.5M
Dissecting recurrent microdeletion syndromes using dual-guide genome editingR01NS093200 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI GUSELLA, JAMES F · 2015 to 2019
$2.9M
Howard Hughes Medical InstituteNCRR NIH HHS S10 RR028832NHGRI NIH HHS RM1 HG008525NIA NIH HHS R01 AG069042NIA NIH HHS U01 AG061835NICHD NIH HHS P50 HD105351NICHD NIH HHS R01 HD096326NIMH NIH HHS R01 MH113279NINDS NIH HHS R01 NS093200
6 · The paper itself

Abstract

Cerebral organoids can be used to gain insights into cell type specific processes perturbed by genetic variants associated with neuropsychiatric disorders. However, robust and scalable phenotyping of organoids remains challenging. Here, we perform RNA sequencing on 71 samples comprising 1,420 cerebral organoids from 25 donors, and describe a framework (Orgo-Seq) to integrate bulk RNA and single-cell RNA sequence data. We apply Orgo-Seq to 16p11.2 deletions and 15q11-13 duplications, two loci associated with autism spectrum disorder, to identify immature neurons and intermediate progenitor cells as critical cell types for 16p11.2 deletions. We further applied Orgo-Seq to identify cell type-specific driver genes. Our work presents a quantitative phenotyping framework to integrate multi-transcriptomic datasets for the identification of cell types and cell type-specific co-expressed driver genes associated with neuropsychiatric disorders.

Indexed as

Autism Spectrum DisorderAutistic DisorderIntellectual DisabilityChromosome DeletionChromosome DisordersChromosomes, Human, Pair 16HumansSequence Analysis, RNASingle-Cell AnalysisTranscriptome

Identifiers

PMID35688811
PMCPMC9187732
OpenAlexW4281715287

What OpenQuestion holds

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LicenceCC BY
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 OpenQuestion graph.