CopyMix : Mixture model based single-cell clustering and copy number profiling using variational inference

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Volume Title

A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä

Date

2024-12

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Mcode

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Language

en

Pages

17

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Computational Biology and Chemistry, Volume 113, pp. 1-17

Abstract

Investigating tumor heterogeneity using single-cell sequencing technologies is imperative to understand how tumors evolve since each cell subpopulation harbors a unique set of genomic features that yields a unique phenotype, which is bound to have clinical relevance. Clustering of cells based on copy number data obtained from single-cell DNA sequencing provides an opportunity to identify different tumor cell subpopulations. Accordingly, computational methods have emerged for single-cell copy number profiling and clustering; however, these two tasks have been handled sequentially by applying various ad-hoc pre- and post-processing steps; hence, a procedure vulnerable to introducing clustering artifacts. We avoid the clustering artifact issues in our method, CopyMix, a Variational Inference for a novel mixture model, by jointly inferring cell clusters and their underlying copy number profile. Our probabilistic graphical model is an improved version of the mixture of hidden Markov models, which is designed uniquely to infer single-cell copy number profiling and clustering. For the evaluation, we used likelihood-ratio test, CH index, Silhouette, V-measure, total variation scores. CopyMix performs well on both biological and simulated data. Our favorable results indicate a considerable potential to obtain clinical impact by using CopyMix in studies of cancer tumor heterogeneity.

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Publisher Copyright: © 2024 The Authors

Keywords

Cancer, Copy number profiling, Mixture models, Single-cell, Tumor clonal decomposition, Variational inference

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Citation

Safinianaini, N, De Souza, C P E, Roth, A, Koptagel, H, Toosi, H & Lagergren, J 2024, ' CopyMix : Mixture model based single-cell clustering and copy number profiling using variational inference ', Computational Biology and Chemistry, vol. 113, 108257, pp. 1-17 . https://doi.org/10.1016/j.compbiolchem.2024.108257