IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-60900-4.html
   My bibliography  Save this article

Cell Marker Accordion: interpretable single-cell and spatial omics annotation in health and disease

Author

Listed:
  • Emma Busarello

    (University of Trento)

  • Giulia Biancon

    (Yale University School of Medicine
    Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico)

  • Ilaria Cimignolo

    (University of Trento)

  • Fabio Lauria

    (CNR Unit at Trento)

  • Zuhairia Ibnat

    (University of Trento)

  • Christian Ramirez

    (University of Trento)

  • Gabriele Tomè

    (University of Trento
    CNR Unit at Trento)

  • Marianna Ciuffreda

    (University of Trento)

  • Giorgia Bucciarelli

    (University of Trento)

  • Alessandro Pilli

    (University of Trento)

  • Stefano Maria Marino

    (University of Trento)

  • Vittorio Bontempi

    (University of Trento)

  • Federica Ress

    (University of Trento)

  • Kristin R. Aass

    (Norwegian University of Science and Technology (NTNU))

  • Jennifer VanOudenhove

    (Yale University School of Medicine)

  • Luca Tiberi

    (University of Trento)

  • Maria Caterina Mione

    (University of Trento)

  • Therese Standal

    (Norwegian University of Science and Technology (NTNU))

  • Paolo Macchi

    (University of Trento)

  • Gabriella Viero

    (CNR Unit at Trento)

  • Stephanie Halene

    (Yale University School of Medicine
    Yale University School of Medicine)

  • Toma Tebaldi

    (University of Trento
    Yale University School of Medicine)

Abstract

Single-cell technologies offer a unique opportunity to explore cellular heterogeneity in health and disease. However, reliable identification of cell types and states represents a bottleneck. Available databases and analysis tools employ dissimilar markers, leading to inconsistent annotations and poor interpretability. Furthermore, current tools focus mostly on physiological cell types, limiting their applicability to disease. We present the Cell Marker Accordion, a user-friendly platform providing automatic annotation and unmatched biological interpretation of single-cell populations, based on consistency weighted markers. We validate our approach on multiple single-cell and spatial datasets from different human and murine tissues, improving annotation accuracy in all cases. Moreover, we show that the Cell Marker Accordion can identify disease-critical cells and pathological processes, extracting potential biomarkers in a wide variety of disease contexts. The breadth of these applications elevates the Cell Marker Accordion as a fast, flexible, faithful and standardized tool to annotate and interpret single-cell and spatial populations in studying physiology and disease.

Suggested Citation

  • Emma Busarello & Giulia Biancon & Ilaria Cimignolo & Fabio Lauria & Zuhairia Ibnat & Christian Ramirez & Gabriele Tomè & Marianna Ciuffreda & Giorgia Bucciarelli & Alessandro Pilli & Stefano Maria Mar, 2025. "Cell Marker Accordion: interpretable single-cell and spatial omics annotation in health and disease," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60900-4
    DOI: 10.1038/s41467-025-60900-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-60900-4
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-025-60900-4?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. Eliza Yankova & Wesley Blackaby & Mark Albertella & Justyna Rak & Etienne Braekeleer & Georgia Tsagkogeorga & Ewa S. Pilka & Demetrios Aspris & Dan Leggate & Alan G. Hendrick & Natalie A. Webster & By, 2021. "Small-molecule inhibition of METTL3 as a strategy against myeloid leukaemia," Nature, Nature, vol. 593(7860), pages 597-601, May.
    2. Nikolaus Rajewsky & Geneviève Almouzni & Stanislaw A. Gorski & Stein Aerts & Ido Amit & Michela G. Bertero & Christoph Bock & Annelien L. Bredenoord & Giacomo Cavalli & Susanna Chiocca & Hans Clevers , 2020. "LifeTime and improving European healthcare through cell-based interceptive medicine," Nature, Nature, vol. 587(7834), pages 377-386, November.
    3. Kenichi Yoshida & Masashi Sanada & Yuichi Shiraishi & Daniel Nowak & Yasunobu Nagata & Ryo Yamamoto & Yusuke Sato & Aiko Sato-Otsubo & Ayana Kon & Masao Nagasaki & George Chalkidis & Yutaka Suzuki & M, 2011. "Frequent pathway mutations of splicing machinery in myelodysplasia," Nature, Nature, vol. 478(7367), pages 64-69, October.
    4. M. Büttner & J. Ostner & C. L. Müller & F. J. Theis & B. Schubert, 2021. "scCODA is a Bayesian model for compositional single-cell data analysis," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    5. Nian Liu & Qing Dai & Guanqun Zheng & Chuan He & Marc Parisien & Tao Pan, 2015. "N6-methyladenosine-dependent RNA structural switches regulate RNA–protein interactions," Nature, Nature, vol. 518(7540), pages 560-564, February.
    6. Antonio De Falco & Francesca Caruso & Xiao-Dong Su & Antonio Iavarone & Michele Ceccarelli, 2023. "A variational algorithm to detect the clonal copy number substructure of tumors from scRNA-seq data," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    7. Nayoung Kim & Hong Kwan Kim & Kyungjong Lee & Yourae Hong & Jong Ho Cho & Jung Won Choi & Jung-Il Lee & Yeon-Lim Suh & Bo Mi Ku & Hye Hyeon Eum & Soyean Choi & Yoon-La Choi & Je-Gun Joung & Woong-Yang, 2020. "Single-cell RNA sequencing demonstrates the molecular and cellular reprogramming of metastatic lung adenocarcinoma," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    8. Nourhan Abdelfattah & Parveen Kumar & Caiyi Wang & Jia-Shiun Leu & William F. Flynn & Ruli Gao & David S. Baskin & Kumar Pichumani & Omkar B. Ijare & Stephanie L. Wood & Suzanne Z. Powell & David L. H, 2022. "Single-cell analysis of human glioma and immune cells identifies S100A4 as an immunotherapy target," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    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. Cristina Leoni & Marian Bataclan & Taku Ito-Kureha & Vigo Heissmeyer & Silvia Monticelli, 2023. "The mRNA methyltransferase Mettl3 modulates cytokine mRNA stability and limits functional responses in mast cells," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Magnus Zethoven & Luciano Martelotto & Andrew Pattison & Blake Bowen & Shiva Balachander & Aidan Flynn & Fernando J. Rossello & Annette Hogg & Julie A. Miller & Zdenek Frysak & Sean Grimmond & Lauren , 2022. "Single-nuclei and bulk-tissue gene-expression analysis of pheochromocytoma and paraganglioma links disease subtypes with tumor microenvironment," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    3. 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.
    4. Benxia Hu & Yuqiang Shi & Feng Xiong & Yi-Ting Chen & Xiaoyu Zhu & Elisa Carrillo & Xingzhao Wen & Nathan Drolet & Chetan Singh Rajpurohit & Xiangmin Xu & Dung-Fang Lee & Claudio Soto & Sheng Zhong & , 2025. "Rewired m6A of promoter antisense RNAs in Alzheimer’s disease regulates neuronal genes in 3D nucleome," Nature Communications, Nature, vol. 16(1), pages 1-20, December.
    5. Yi Huang & Anyongqi Wang & Wenjiang Zhou & Baoguo Li & Linshan Zhang & Agata M. Rudolf & Zengguang Jin & Catherine Hambly & Guanlin Wang & John R. Speakman, 2024. "Maternal dietary fat during lactation shapes single nucleus transcriptomic profile of postnatal offspring hypothalamus in a sexually dimorphic manner in mice," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    6. Valentin Picant & Lara Revol-Bauz & Laurie Tonon & Timothée Casini & Aurélien Voissière & Dominique Poujol & Emilie Picard & Céline Rodriguez & Cyril Degletagne & Emily Sible & Uzma Hasan & Anthony Fe, 2025. "Interleukin-35 impairs human NK cell effector functions and induces their ILC1-like conversion with tissue residency features," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    7. Ya-Ping Yen & Ting-Hsiang Lung & Ee Shan Liau & Chuan-Che Wu & Guan-Lin Huang & Fang-Yu Hsu & Mien Chang & Zheng-Dao Yang & Chia-Yi Huang & Zhong Zheng & Wei Zhao & Jui-Hung Hung & Chuan He & Qing Nie, 2025. "The motor neuron m6A repertoire governs neuronal homeostasis and FTO inhibition mitigates ALS symptom manifestation," Nature Communications, Nature, vol. 16(1), pages 1-23, December.
    8. Siqi Chen & Yingyu Wang & Jessica Dang & Nuozi Song & Xiaoxin Chen & Jinhui Wang & Guo N. Huang & Christine E. Brown & Jianhua Yu & Irving L. Weissman & Steven T. Rosen & Mingye Feng, 2025. "CAR macrophages with built-In CD47 blocker combat tumor antigen heterogeneity and activate T cells via cross-presentation," Nature Communications, Nature, vol. 16(1), pages 1-20, December.
    9. Yuwei Zhang & Jieyu Zhao & Xiaona Chen & Yulong Qiao & Jinjin Kang & Xiaofan Guo & Feng Yang & Kaixin Lyu & Yiliang Ding & Yu Zhao & Hao Sun & Chun-Kit Kwok & Huating Wang, 2024. "DHX36 binding induces RNA structurome remodeling and regulates RNA abundance via m6A reader YTHDF1," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    10. Matthew C. Hill & Bridget Simonson & Carolina Roselli & Ling Xiao & Caroline N. Herndon & Mark Chaffin & Helene Mantineo & Ondine Atwa & Harshit Bhasin & Yasmine Guedira & Kenneth C. Bedi & Kenneth B., 2024. "Large-scale single-nuclei profiling identifies role for ATRNL1 in atrial fibrillation," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    11. Zhenlin Yang & He Tian & Xiaowei Chen & Bozhao Li & Guangyu Bai & Qingyuan Cai & Jiachen Xu & Wei Guo & Shuaibo Wang & Yue Peng & Qing Liang & Liyan Xue & Shugeng Gao, 2024. "Single-cell sequencing reveals immune features of treatment response to neoadjuvant immunochemotherapy in esophageal squamous cell carcinoma," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    12. Arezou Rahimi & Luis A. Vale-Silva & Maria Fälth Savitski & Jovan Tanevski & Julio Saez-Rodriguez, 2024. "DOT: a flexible multi-objective optimization framework for transferring features across single-cell and spatial omics," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    13. Gregor Werba & Daniel Weissinger & Emily A. Kawaler & Ende Zhao & Despoina Kalfakakou & Surajit Dhara & Lidong Wang & Heather B. Lim & Grace Oh & Xiaohong Jing & Nina Beri & Lauren Khanna & Tamas Gond, 2023. "Single-cell RNA sequencing reveals the effects of chemotherapy on human pancreatic adenocarcinoma and its tumor microenvironment," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    14. Lulu Shang & Peijun Wu & Xiang Zhou, 2025. "Statistical identification of cell type-specific spatially variable genes in spatial transcriptomics," Nature Communications, Nature, vol. 16(1), pages 1-20, December.
    15. Jasmin Bartl & Marco Zanini & Flavia Bernardi & Antoine Forget & Lena Blümel & Julie Talbot & Daniel Picard & Nan Qin & Gabriele Cancila & Qingsong Gao & Soumav Nath & Idriss Mahoungou Koumba & Mariet, 2022. "The HHIP-AS1 lncRNA promotes tumorigenicity through stabilization of dynein complex 1 in human SHH-driven tumors," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    16. Shreya Johri & Kevin Bi & Breanna M. Titchen & Jingxin Fu & Jake Conway & Jett P. Crowdis & Natalie I. Vokes & Zenghua Fan & Lawrence Fong & Jihye Park & David Liu & Meng Xiao He & Eliezer M. Van Alle, 2025. "Dissecting tumor cell programs through group biology estimation in clinical single-cell transcriptomics," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    17. Hanna Schwaemmle & Hadrien Soldati & Nikolaos M. R. Lykoskoufis & Mylène Docquier & Alexandre Hainard & Simon M. G. Braun, 2025. "CRISPR screen decodes SWI/SNF chromatin remodeling complex assembly," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    18. Frank A. Giordano & Julian P. Layer & Sonia Leonardelli & Lea L. Friker & Roberta Turiello & Dillon Corvino & Thomas Zeyen & Christina Schaub & Wolf Müller & Elena Sperk & Leonard Christopher Schmeel , 2024. "L-RNA aptamer-based CXCL12 inhibition combined with radiotherapy in newly-diagnosed glioblastoma: dose escalation of the phase I/II GLORIA trial," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    19. Jorge Mata-Garrido & Yao Xiang & Yunhua Chang-Marchand & Caroline Reisacher & Elisabeth Ageron & Ida Chiara Guerrera & Iñigo Casafont & Aurelia Bruneau & Claire Cherbuy & Xavier Treton & Anne Dumay & , 2022. "The Heterochromatin protein 1 is a regulator in RNA splicing precision deficient in ulcerative colitis," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    20. 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.

    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:16:y:2025:i:1:d:10.1038_s41467-025-60900-4. 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.