IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-51649-3.html
   My bibliography  Save this article

Robust identification of perturbed cell types in single-cell RNA-seq data

Author

Listed:
  • Phillip B. Nicol

    (Harvard University)

  • Danielle Paulson

    (Harvard University)

  • Gege Qian

    (University of California San Diego School of Medicine)

  • X. Shirley Liu

    (Dana-Farber Cancer Institute)

  • Rafael Irizarry

    (Dana-Farber Cancer Institute)

  • Avinash D. Sahu

    (University of New Mexico Comprehensive Cancer Center)

Abstract

Single-cell transcriptomics has emerged as a powerful tool for understanding how different cells contribute to disease progression by identifying cell types that change across diseases or conditions. However, detecting changing cell types is challenging due to individual-to-individual and cohort-to-cohort variability and naive approaches based on current computational tools lead to false positive findings. To address this, we propose a computational tool, scDist, based on a mixed-effects model that provides a statistically rigorous and computationally efficient approach for detecting transcriptomic differences. By accurately recapitulating known immune cell relationships and mitigating false positives induced by individual and cohort variation, we demonstrate that scDist outperforms current methods in both simulated and real datasets, even with limited sample sizes. Through the analysis of COVID-19 and immunotherapy datasets, scDist uncovers transcriptomic perturbations in dendritic cells, plasmacytoid dendritic cells, and FCER1G+NK cells, that provide new insights into disease mechanisms and treatment responses. As single-cell datasets continue to expand, our faster and statistically rigorous method offers a robust and versatile tool for a wide range of research and clinical applications, enabling the investigation of cellular perturbations with implications for human health and disease.

Suggested Citation

  • Phillip B. Nicol & Danielle Paulson & Gege Qian & X. Shirley Liu & Rafael Irizarry & Avinash D. Sahu, 2024. "Robust identification of perturbed cell types in single-cell RNA-seq data," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51649-3
    DOI: 10.1038/s41467-024-51649-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-51649-3
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-51649-3?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Sanjeev Mariathasan & Shannon J. Turley & Dorothee Nickles & Alessandra Castiglioni & Kobe Yuen & Yulei Wang & Edward E. Kadel III & Hartmut Koeppen & Jillian L. Astarita & Rafael Cubas & Suchit Jhunj, 2018. "TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells," Nature, Nature, vol. 554(7693), pages 544-548, February.
    2. Kip D. Zimmerman & Mark A. Espeland & Carl D. Langefeld, 2021. "A practical solution to pseudoreplication bias in single-cell studies," Nature Communications, Nature, vol. 12(1), pages 1-9, December.
    3. Beth A. Helmink & Sangeetha M. Reddy & Jianjun Gao & Shaojun Zhang & Rafet Basar & Rohit Thakur & Keren Yizhak & Moshe Sade-Feldman & Jorge Blando & Guangchun Han & Vancheswaran Gopalakrishnan & Yuanx, 2020. "B cells and tertiary lymphoid structures promote immunotherapy response," Nature, Nature, vol. 577(7791), pages 549-555, January.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Marina Baretti & Ludmila Danilova & Jennifer N. Durham & Courtney B. Betts & Leslie Cope & Dimitrios N. Sidiropoulos & Joseph A. Tandurella & Soren Charmsaz & Nicole Gross & Alexei Hernandez & Won Jin, 2024. "Entinostat in combination with nivolumab in metastatic pancreatic ductal adenocarcinoma: a phase 2 clinical trial," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Martin Lauss & Bengt Phung & Troels Holz Borch & Katja Harbst & Kamila Kaminska & Anna Ebbesson & Ingrid Hedenfalk & Joan Yuan & Kari Nielsen & Christian Ingvar & Ana Carneiro & Karolin Isaksson & Kri, 2024. "Molecular patterns of resistance to immune checkpoint blockade in melanoma," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    3. Jing Liu & Xia Bu & Chen Chu & Xiaoming Dai & John M. Asara & Piotr Sicinski & Gordon J. Freeman & Wenyi Wei, 2023. "PRMT1 mediated methylation of cGAS suppresses anti-tumor immunity," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    4. Guo Li & Saranya Srinivasan & Liwen Wang & Chaoyu Ma & Kai Guo & Wenhao Xiao & Wei Liao & Shruti Mishra & Xin Zhang & Yuanzheng Qiu & Qianjin Lu & Yong Liu & Nu Zhang, 2022. "TGF-β-dependent lymphoid tissue residency of stem-like T cells limits response to tumor vaccine," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    5. Nanda Horeweg & Hagma H. Workel & Dominik Loiero & David N. Church & Lisa Vermij & Alicia Léon-Castillo & Ricki T. Krog & Stephanie M. Boer & Remi A. Nout & Melanie E. Powell & Linda R. Mileshkin & He, 2022. "Tertiary lymphoid structures critical for prognosis in endometrial cancer patients," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    6. Mengxue Zhou & Jiaxin Wang & Jiaxing Pan & Hui Wang & Lujia Huang & Bo Hou & Yi Lai & Fengyang Wang & Qingxiang Guan & Feng Wang & Zhiai Xu & Haijun Yu, 2023. "Nanovesicles loaded with a TGF-β receptor 1 inhibitor overcome immune resistance to potentiate cancer immunotherapy," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    7. Han Luo & Xuyang Xia & Li-Bin Huang & Hyunsu An & Minyuan Cao & Gyeong Dae Kim & Hai-Ning Chen & Wei-Han Zhang & Yang Shu & Xiangyu Kong & Zhixiang Ren & Pei-Heng Li & Yang Liu & Huairong Tang & Rongh, 2022. "Pan-cancer single-cell analysis reveals the heterogeneity and plasticity of cancer-associated fibroblasts in the tumor microenvironment," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    8. Akshay J. Patel & Zena N. Willsmore & Naeem Khan & Alex Richter & Babu Naidu & Mark T. Drayson & Sophie Papa & Andrew Cope & Sophia N. Karagiannis & Esperanza Perucha & Gary W. Middleton, 2022. "Regulatory B cell repertoire defects predispose lung cancer patients to immune-related toxicity following checkpoint blockade," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    9. Spencer R. Rosario & Mark D. Long & Shanmuga Chilakapati & Eduardo Cortes Gomez & Sebastiano Battaglia & Prashant K. Singh & Jianmin Wang & Katy Wang & Kristopher Attwood & Suzanne M. Hess & AJ Robert, 2024. "Integrative multi-omics analysis uncovers tumor-immune-gut axis influencing immunotherapy outcomes in ovarian cancer," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    10. Qian-Yue Zhang & Xiao-Ping Ye & Zheng Zhou & Chen-Fang Zhu & Rui Li & Ya Fang & Rui-Jia Zhang & Lu Li & Wei Liu & Zheng Wang & Shi-Yang Song & Sang-Yu Lu & Shuang-Xia Zhao & Jian-Nan Lin & Huai-Dong S, 2022. "Lymphocyte infiltration and thyrocyte destruction are driven by stromal and immune cell components in Hashimoto’s thyroiditis," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    11. Rana Falahat & Anders Berglund & Patricio Perez-Villarroel & Ryan M. Putney & Imene Hamaidi & Sungjune Kim & Shari Pilon-Thomas & Glen N. Barber & James J. Mulé, 2023. "Epigenetic state determines the in vivo efficacy of STING agonist therapy," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    12. Li Yuan & Guo-Dong Jia & Xiao-Fei Lv & Si-Yi Xie & Shan-Shan Guo & Da-Feng Lin & Li-Ting Liu & Dong-Hua Luo & Yi-Fu Li & Shen-Wen Deng & Ling Guo & Mu-Sheng Zeng & Xiu-Yu Cai & Sai-Lan Liu & Xue-Song , 2023. "Camrelizumab combined with apatinib in patients with first-line platinum-resistant or PD-1 inhibitor resistant recurrent/metastatic nasopharyngeal carcinoma: a single-arm, phase 2 trial," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    13. Jieqiong Liu & Ying Wang & Zhenluan Tian & Ying Lin & Hengyu Li & Zhaowen Zhu & Qiang Liu & Shicheng Su & Yinduo Zeng & Weijuan Jia & Yaping Yang & Shengqiang Xu & Herui Yao & Wen Jiang & Erwei Song, 2022. "Multicenter phase II trial of Camrelizumab combined with Apatinib and Eribulin in heavily pretreated patients with advanced triple-negative breast cancer," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    14. Matthew T. Campbell & Surena F. Matin & Alda L. Tam & Rahul A. Sheth & Kamran Ahrar & Rebecca S. Tidwell & Priya Rao & Jose A. Karam & Christopher G. Wood & Nizar M. Tannir & Eric Jonasch & Jianjun Ga, 2021. "Pilot study of Tremelimumab with and without cryoablation in patients with metastatic renal cell carcinoma," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    15. Zhenzhen Xun & Xinyu Ding & Yao Zhang & Benyan Zhang & Shujing Lai & Duowu Zou & Junke Zheng & Guoqiang Chen & Bing Su & Leng Han & Youqiong Ye, 2023. "Reconstruction of the tumor spatial microenvironment along the malignant-boundary-nonmalignant axis," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    16. Jessy A. Slota & Lise Lamoureux & Kathy L. Frost & Babu V. Sajesh & Stephanie A. Booth, 2024. "Single-cell transcriptomics unveils molecular signatures of neuronal vulnerability in a mouse model of prion disease that overlap with Alzheimer’s disease," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    17. Saba Nayar & Jason D. Turner & Saba Asam & Eanna Fennell & Matthew Pugh & Serena Colafrancesco & Onorina Berardicurti & Charlotte G. Smith & Joe Flint & Ana Teodosio & Valentina Iannizzotto & David H., 2025. "Molecular and spatial analysis of tertiary lymphoid structures in Sjogren’s syndrome," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    18. Alessandra Nerviani & Marie-Astrid Boutet & Giulia Maria Ghirardi & Katriona Goldmann & Elisabetta Sciacca & Felice Rivellese & Elena Pontarini & Edoardo Prediletto & Federico Abatecola & Mattia Calis, 2024. "Axl and MerTK regulate synovial inflammation and are modulated by IL-6 inhibition in rheumatoid arthritis," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    19. Suhas V. Vasaikar & Adam K. Savage & Qiuyu Gong & Elliott Swanson & Aarthi Talla & Cara Lord & Alexander T. Heubeck & Julian Reading & Lucas T. Graybuck & Paul Meijer & Troy R. Torgerson & Peter J. Sk, 2023. "A comprehensive platform for analyzing longitudinal multi-omics data," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    20. Yang Liu & Shuang-Yan Ye & Shuai He & Dong-Mei Chi & Xiu-Zhi Wang & Yue-Feng Wen & Dong Ma & Run-Cong Nie & Pu Xiang & You Zhou & Zhao-Hui Ruan & Rou-Jun Peng & Chun-Ling Luo & Pan-Pan Wei & Guo-Wang , 2024. "Single-cell and spatial transcriptome analyses reveal tertiary lymphoid structures linked to tumour progression and immunotherapy response in nasopharyngeal carcinoma," Nature Communications, Nature, vol. 15(1), pages 1-22, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51649-3. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.