IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-50618-0.html
   My bibliography  Save this article

Community assessment of methods to deconvolve cellular composition from bulk gene expression

Author

Listed:
  • Brian S. White

    (Sage Bionetworks
    The Jackson Laboratory for Genomic Medicine)

  • Aurélien Reyniès

    (INSERM U1138, Université Paris Cité)

  • Aaron M. Newman

    (Stanford University
    Stanford University)

  • Joshua J. Waterfall

    (PSL Research University)

  • Andrew Lamb

    (Sage Bionetworks)

  • Florent Petitprez

    (Ligue Nationale Contre le Cancer
    University of Edinburgh)

  • Yating Lin

    (Xiamen University)

  • Rongshan Yu

    (Xiamen University)

  • Martin E. Guerrero-Gimenez

    (National University of Cuyo)

  • Sergii Domanskyi

    (Michigan State University)

  • Gianni Monaco

    (BIOGEM Institute of Molecular Biology and Genetics)

  • Verena Chung

    (Sage Bionetworks)

  • Jineta Banerjee

    (Sage Bionetworks)

  • Daniel Derrick

    (Oregon Health & Science University)

  • Alberto Valdeolivas

    (Institute for Computational Biomedicine)

  • Haojun Li

    (Xiamen University)

  • Xu Xiao

    (Xiamen University)

  • Shun Wang

    (Cancer Hospital, Chinese Aacdemy of Medical Science)

  • Frank Zheng

    (AmoyDx)

  • Wenxian Yang

    (Aginome Scientific)

  • Carlos A. Catania

    (National University of Cuyo)

  • Benjamin J. Lang

    (Harvard Medical School)

  • Thomas J. Bertus

    (Michigan State University)

  • Carlo Piermarocchi

    (Michigan State University)

  • Francesca P. Caruso

    (BIOGEM Institute of Molecular Biology and Genetics)

  • Michele Ceccarelli

    (BIOGEM Institute of Molecular Biology and Genetics
    University of Miami Miller School of Medicine)

  • Thomas Yu

    (Sage Bionetworks)

  • Xindi Guo

    (Sage Bionetworks)

  • Julie Bletz

    (Sage Bionetworks)

  • John Coller

    (Stanford University School of Medicine)

  • Holden Maecker

    (Stanford University School of Medicine)

  • Caroline Duault

    (Stanford University School of Medicine)

  • Vida Shokoohi

    (Stanford University School of Medicine)

  • Shailja Patel

    (Stanford University School of Medicine)

  • Joanna E. Liliental

    (Stanford University School of Medicine)

  • Stockard Simon

    (Sage Bionetworks)

  • Julio Saez-Rodriguez

    (Institute for Computational Biomedicine)

  • Laura M. Heiser

    (Oregon Health & Science University)

  • Justin Guinney

    (Sage Bionetworks)

  • Andrew J. Gentles

    (Stanford University
    Stanford University School of Medicine
    Stanford University)

Abstract

We evaluate deconvolution methods, which infer levels of immune infiltration from bulk expression of tumor samples, through a community-wide DREAM Challenge. We assess six published and 22 community-contributed methods using in vitro and in silico transcriptional profiles of admixed cancer and healthy immune cells. Several published methods predict most cell types well, though they either were not trained to evaluate all functional CD8+ T cell states or do so with low accuracy. Several community-contributed methods address this gap, including a deep learning-based approach, whose strong performance establishes the applicability of this paradigm to deconvolution. Despite being developed largely using immune cells from healthy tissues, deconvolution methods predict levels of tumor-derived immune cells well. Our admixed and purified transcriptional profiles will be a valuable resource for developing deconvolution methods, including in response to common challenges we observe across methods, such as sensitive identification of functional CD4+ T cell states.

Suggested Citation

  • Brian S. White & Aurélien Reyniès & Aaron M. Newman & Joshua J. Waterfall & Andrew Lamb & Florent Petitprez & Yating Lin & Rongshan Yu & Martin E. Guerrero-Gimenez & Sergii Domanskyi & Gianni Monaco &, 2024. "Community assessment of methods to deconvolve cellular composition from bulk gene expression," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50618-0
    DOI: 10.1038/s41467-024-50618-0
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-50618-0
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-50618-0?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. Haoyang Li & Juexiao Zhou & Zhongxiao Li & Siyuan Chen & Xingyu Liao & Bin Zhang & Ruochi Zhang & Yu Wang & Shiwei Sun & Xin Gao, 2023. "A comprehensive benchmarking with practical guidelines for cellular deconvolution of spatial transcriptomics," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    2. Jordi Barretina & Giordano Caponigro & Nicolas Stransky & Kavitha Venkatesan & Adam A. Margolin & Sungjoon Kim & Christopher J.Wilson & Joseph Lehár & Gregory V. Kryukov & Dmitriy Sonkin & Anupama Red, 2012. "Addendum: The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity," Nature, Nature, vol. 492(7428), pages 290-290, December.
    3. Jordi Barretina & Giordano Caponigro & Nicolas Stransky & Kavitha Venkatesan & Adam A. Margolin & Sungjoon Kim & Christopher J. Wilson & Joseph Lehár & Gregory V. Kryukov & Dmitriy Sonkin & Anupama Re, 2012. "The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity," Nature, Nature, vol. 483(7391), pages 603-607, March.
    4. Dan R. Robinson & Yi-Mi Wu & Robert J. Lonigro & Pankaj Vats & Erin Cobain & Jessica Everett & Xuhong Cao & Erica Rabban & Chandan Kumar-Sinha & Victoria Raymond & Scott Schuetze & Ajjai Alva & Javed , 2017. "Integrative clinical genomics of metastatic cancer," Nature, Nature, vol. 548(7667), pages 297-303, August.
    5. S. Y. Cindy Yang & Scott C. Lien & Ben X. Wang & Derek L. Clouthier & Youstina Hanna & Iulia Cirlan & Kelsey Zhu & Jeffrey P. Bruce & Samah El Ghamrasni & Marco A. J. Iafolla & Marc Oliva & Aaron R. H, 2021. "Pan-cancer analysis of longitudinal metastatic tumors reveals genomic alterations and immune landscape dynamics associated with pembrolizumab sensitivity," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    6. Florent Petitprez & Aurélien Reyniès & Emily Z. Keung & Tom Wei-Wu Chen & Cheng-Ming Sun & Julien Calderaro & Yung-Ming Jeng & Li-Ping Hsiao & Laetitia Lacroix & Antoine Bougoüin & Marco Moreira & Gui, 2020. "B cells are associated with survival and immunotherapy response in sarcoma," Nature, Nature, vol. 577(7791), pages 556-560, January.
    7. Konstantin Zaitsev & Monika Bambouskova & Amanda Swain & Maxim N. Artyomov, 2019. "Complete deconvolution of cellular mixtures based on linearity of transcriptional signatures," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    8. Amodio, S. & D’Ambrosio, A. & Siciliano, R., 2016. "Accurate algorithms for identifying the median ranking when dealing with weak and partial rankings under the Kemeny axiomatic approach," European Journal of Operational Research, Elsevier, vol. 249(2), pages 667-676.
    9. 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. Guidantonio Malagoli Tagliazucchi & Anna J. Wiecek & Eloise Withnell & Maria Secrier, 2023. "Genomic and microenvironmental heterogeneity shaping epithelial-to-mesenchymal trajectories in cancer," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    2. 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.
    3. Seungyeul Yoo & Abhilasha Sinha & Dawei Yang & Nasser K. Altorki & Radhika Tandon & Wenhui Wang & Deebly Chavez & Eunjee Lee & Ayushi S. Patel & Takashi Sato & Ranran Kong & Bisen Ding & Eric E. Schad, 2022. "Integrative network analysis of early-stage lung adenocarcinoma identifies aurora kinase inhibition as interceptor of invasion and progression," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    4. 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.
    5. Alon Stern & Mariam Fokra & Boris Sarvin & Ahmad Abed Alrahem & Won Dong Lee & Elina Aizenshtein & Nikita Sarvin & Tomer Shlomi, 2023. "Inferring mitochondrial and cytosolic metabolism by coupling isotope tracing and deconvolution," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    6. Yanli Liu & Zhong Wu & Jin Zhou & Dinesh K. A. Ramadurai & Katelyn L. Mortenson & Estrella Aguilera-Jimenez & Yifei Yan & Xiaojun Yang & Alison M. Taylor & Katherine E. Varley & Jason Gertz & Peter S., 2021. "A predominant enhancer co-amplified with the SOX2 oncogene is necessary and sufficient for its expression in squamous cancer," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    7. Sayantani Ghosh Dastidar & Bony Kumar & Bo Lauckner & Damien Parrello & Danielle Perley & Maria Vlasenok & Antariksh Tyagi & Nii Koney-Kwaku Koney & Ata Abbas & Sergei Nechaev, 2023. "Transcriptional responses of cancer cells to heat shock-inducing stimuli involve amplification of robust HSF1 binding," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    8. Sumana Srivatsa & Hesam Montazeri & Gaia Bianco & Mairene Coto-Llerena & Mattia Marinucci & Charlotte K. Y. Ng & Salvatore Piscuoglio & Niko Beerenwinkel, 2022. "Discovery of synthetic lethal interactions from large-scale pan-cancer perturbation screens," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    9. 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.
    10. Cemal Erdem & Sean M. Gross & Laura M. Heiser & Marc R. Birtwistle, 2023. "MOBILE pipeline enables identification of context-specific networks and regulatory mechanisms," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    11. 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.
    12. 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.
    13. 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.
    14. Souleymane Abdoul-Azize & Rihab Hami & Gaetan Riou & Céline Derambure & Camille Charbonnier & Jean-Pierre Vannier & Monica L. Guzman & Pascale Schneider & Olivier Boyer, 2024. "Glucocorticoids paradoxically promote steroid resistance in B cell acute lymphoblastic leukemia through CXCR4/PLC signaling," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    15. 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.
    16. Philip East & Gavin P. Kelly & Dhruva Biswas & Michela Marani & David C. Hancock & Todd Creasy & Kris Sachsenmeier & Charles Swanton & Julian Downward & Sophie de Carné Trécesson, 2022. "RAS oncogenic activity predicts response to chemotherapy and outcome in lung adenocarcinoma," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    17. Caterina Bartolacci & Cristina Andreani & Gonçalo Vale & Stefano Berto & Margherita Melegari & Anna Colleen Crouch & Dodge L. Baluya & George Kemble & Kurt Hodges & Jacqueline Starrett & Katerina Poli, 2022. "Targeting de novo lipogenesis and the Lands cycle induces ferroptosis in KRAS-mutant lung cancer," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    18. Sanju Sinha & Karina Barbosa & Kuoyuan Cheng & Mark D. M. Leiserson & Prashant Jain & Anagha Deshpande & David M. Wilson & Bríd M. Ryan & Ji Luo & Ze’ev A. Ronai & Joo Sang Lee & Aniruddha J. Deshpand, 2021. "A systematic genome-wide mapping of oncogenic mutation selection during CRISPR-Cas9 genome editing," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    19. Carolin Ector & Christoph Schmal & Jeff Didier & Sébastien De Landtsheer & Anna-Marie Finger & Francesca Müller-Marquardt & Johannes H. Schulte & Thomas Sauter & Ulrich Keilholz & Hanspeter Herzel & A, 2024. "Time-of-day effects of cancer drugs revealed by high-throughput deep phenotyping," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    20. Zheqi Li & Olivia McGinn & Yang Wu & Amir Bahreini & Nolan M. Priedigkeit & Kai Ding & Sayali Onkar & Caleb Lampenfeld & Carol A. Sartorius & Lori Miller & Margaret Rosenzweig & Ofir Cohen & Nikhil Wa, 2022. "ESR1 mutant breast cancers show elevated basal cytokeratins and immune activation," Nature Communications, Nature, vol. 13(1), pages 1-18, 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_s41467-024-50618-0. 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.