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A variational algorithm to detect the clonal copy number substructure of tumors from scRNA-seq data

Author

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  • Antonio De Falco

    (University of Naples ‘Federico II’
    BIOGEM Institute of Molecular Biology and Genetics)

  • Francesca Caruso

    (University of Naples ‘Federico II’
    BIOGEM Institute of Molecular Biology and Genetics)

  • Xiao-Dong Su

    (Peking University)

  • Antonio Iavarone

    (University of Miami, Miller School of Medicine
    University of Miami, Miller School of Medicine)

  • Michele Ceccarelli

    (University of Naples ‘Federico II’
    BIOGEM Institute of Molecular Biology and Genetics)

Abstract

Single-cell RNA sequencing is the reference technology to characterize the composition of the tumor microenvironment and to study tumor heterogeneity at high resolution. Here we report Single CEll Variational ANeuploidy analysis (SCEVAN), a fast variational algorithm for the deconvolution of the clonal substructure of tumors from single-cell RNA-seq data. It uses a multichannel segmentation algorithm exploiting the assumption that all the cells in a given copy number clone share the same breakpoints. Thus, the smoothed expression profile of every individual cell constitutes part of the evidence of the copy number profile in each subclone. SCEVAN can automatically and accurately discriminate between malignant and non-malignant cells, resulting in a practical framework to analyze tumors and their microenvironment. We apply SCEVAN to datasets encompassing 106 samples and 93,322 cells from different tumor types and technologies. We demonstrate its application to characterize the intratumor heterogeneity and geographic evolution of malignant brain tumors.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36790-9
    DOI: 10.1038/s41467-023-36790-9
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    1. Véronique Frattini & Stefano M. Pagnotta & Tala & Jerry J. Fan & Marco V. Russo & Sang Bae Lee & Luciano Garofano & Jing Zhang & Peiguo Shi & Genevieve Lewis & Heloise Sanson & Vanessa Frederick & Ang, 2018. "A metabolic function of FGFR3-TACC3 gene fusions in cancer," Nature, Nature, vol. 553(7687), pages 222-227, January.
    2. Ruiyang Liu & Qingsong Gao & Steven M. Foltz & Jared S. Fowles & Lijun Yao & Julia Tianjiao Wang & Song Cao & Hua Sun & Michael C. Wendl & Sunantha Sethuraman & Amila Weerasinghe & Michael P. Rettig &, 2021. "Co-evolution of tumor and immune cells during progression of multiple myeloma," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    3. Kosuke Yoshihara & Maria Shahmoradgoli & Emmanuel Martínez & Rahulsimham Vegesna & Hoon Kim & Wandaliz Torres-Garcia & Victor Treviño & Hui Shen & Peter W. Laird & Douglas A. Levine & Scott L. Carter , 2013. "Inferring tumour purity and stromal and immune cell admixture from expression data," Nature Communications, Nature, vol. 4(1), pages 1-11, December.
    4. Itay Tirosh & Andrew S. Venteicher & Christine Hebert & Leah E. Escalante & Anoop P. Patel & Keren Yizhak & Jonathan M. Fisher & Christopher Rodman & Christopher Mount & Mariella G. Filbin & Cyril Nef, 2016. "Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma," Nature, Nature, vol. 539(7628), pages 309-313, November.
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    1. Zhixing Zhong & Junchen Hou & Zhixian Yao & Lei Dong & Feng Liu & Junqiu Yue & Tiantian Wu & Junhua Zheng & Gaoliang Ouyang & Chaoyong Yang & Jia Song, 2024. "Domain generalization enables general cancer cell annotation in single-cell and spatial transcriptomics," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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