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

Author

Listed:
  • Elaine T. Lim

    (University of Massachusetts Chan Medical School
    University of Massachusetts Chan Medical School
    University of Massachusetts Chan Medical School
    University of Massachusetts Chan Medical School)

  • Yingleong Chan

    (University of Massachusetts Chan Medical School
    University of Massachusetts Chan Medical School
    University of Massachusetts Chan Medical School)

  • Pepper Dawes

    (University of Massachusetts Chan Medical School
    University of Massachusetts Chan Medical School
    University of Massachusetts Chan Medical School
    University of Massachusetts Chan Medical School)

  • Xiaoge Guo

    (Harvard Medical School
    Harvard University)

  • Serkan Erdin

    (Massachusetts General Hospital
    Massachusetts General Hospital
    Broad Institute of MIT and Harvard)

  • Derek J. C. Tai

    (Massachusetts General Hospital
    Massachusetts General Hospital
    Broad Institute of MIT and Harvard
    Massachusetts General Hospital)

  • Songlei Liu

    (Harvard Medical School
    Harvard University)

  • Julia M. Reichert

    (University of Massachusetts Chan Medical School
    University of Massachusetts Chan Medical School
    University of Massachusetts Chan Medical School)

  • Mannix J. Burns

    (University of Massachusetts Chan Medical School
    University of Massachusetts Chan Medical School
    University of Massachusetts Chan Medical School
    University of Massachusetts Chan Medical School)

  • Ying Kai Chan

    (Harvard Medical School
    Harvard University)

  • Jessica J. Chiang

    (Harvard Medical School
    Harvard University)

  • Katharina Meyer

    (Harvard Medical School)

  • Xiaochang Zhang

    (The University of Chicago
    The University of Chicago)

  • Christopher A. Walsh

    (Broad Institute of MIT and Harvard
    Boston Children’s Hospital
    Boston Children’s Hospital
    Howard Hughes Medical Institute)

  • Bruce A. Yankner

    (Harvard Medical School)

  • Soumya Raychaudhuri

    (Broad Institute of MIT and Harvard
    Brigham and Women’s Hospital and Harvard Medical School
    Brigham and Women’s Hospital and Harvard Medical School
    University of Manchester)

  • Joel N. Hirschhorn

    (Harvard Medical School
    Broad Institute of MIT and Harvard
    Boston Children’s Hospital
    Boston Children’s Hospital)

  • James F. Gusella

    (Harvard Medical School
    Massachusetts General Hospital
    Broad Institute of MIT and Harvard
    Harvard University)

  • Michael E. Talkowski

    (Massachusetts General Hospital
    Massachusetts General Hospital
    Broad Institute of MIT and Harvard
    Massachusetts General Hospital)

  • George M. Church

    (Harvard Medical School
    Harvard University)

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.

Suggested Citation

  • 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 & Jessica J. Chiang & Katharina Meyer & , 2022. "Orgo-Seq integrates single-cell and bulk transcriptomic data to identify cell type specific-driver genes associated with autism spectrum disorder," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30968-3
    DOI: 10.1038/s41467-022-30968-3
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