Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Comparative Analysis of Cell Mixtures Deconvolution and Gene Signatures Generated for Blood, Immune and Cancer Cells

Version 1 : Received: 26 April 2023 / Approved: 27 April 2023 / Online: 27 April 2023 (10:34:59 CEST)

A peer-reviewed article of this Preprint also exists.

Alonso-Moreda, N.; Berral-González, A.; De La Rosa, E.; González-Velasco, O.; Sánchez-Santos, J.M.; De Las Rivas, J. Comparative Analysis of Cell Mixtures Deconvolution and Gene Signatures Generated for Blood, Immune and Cancer Cells. Int. J. Mol. Sci. 2023, 24, 10765. Alonso-Moreda, N.; Berral-González, A.; De La Rosa, E.; González-Velasco, O.; Sánchez-Santos, J.M.; De Las Rivas, J. Comparative Analysis of Cell Mixtures Deconvolution and Gene Signatures Generated for Blood, Immune and Cancer Cells. Int. J. Mol. Sci. 2023, 24, 10765.

Abstract

In the last two decades many detailed full transcriptomic studies on complex biological samples have been published and included in large gene expression repositories. These studies primarily provide bulk expression signal for each sample, including multiple cell-types mixed within the global signal. The cellular heterogeneity in these mixtures does not allow the activity of specific genes in specific cell types to be identified. Therefore, inferring relative cellular composition is a very powerful tool to achieve a more accurate molecular profiling of complex biological samples. In recent decades, computational techniques have been developed to solve this problem by applying cell deconvolution methods, designed to decompose cell mixtures into their cellular components and calculate the relative proportions of these elements. Some of them, only calculate the cell proportions (supervised methods), while other deconvolution algorithms can also identify the gene signatures specific for each cell type (unsupervised methods). In these work, five deconvolution methods (CIBERSORT, FARDEEP, DECONICA, LINSEED and ABIS) were implemented and used to analyze blood and immune cells, and also cancer cells, in complex mixture samples (using three bulk expression datasets). Our study provides three analytical tools (corrplots, cell-signature plots and bar-mixture plots) that allow a thorough comparative analysis of the cell mixture data. The work indicates that CIBERSORT is a robust method optimized for the identification of immune cell-types, but not as efficient in the identification of cancer cells. We also observed that LINSEED is a very powerful unsupervised method that provides precise and specific gene signatures for each of the five main immune cell-types analyzed: neutrophils and monocytes (in the myeloid lineage), B-cells, NK cells and T-cells (in the lymphoid lineage).

Keywords

cell mixture; deconvolution; immune cells; blood cells; cancer cells; gene signature; bioinformatics

Subject

Biology and Life Sciences, Life Sciences

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