PuSH - Publication Server of Helmholtz Zentrum München: sNucConv: A bulk RNA-seq deconvolution method trained on single-nucleus RNA-seq data to estimate cell-type composition of human adipose tissues.

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Sorek, G.* ; Haim, Y.* ; Chalifa-Caspi, V.* ; Lazarescu, O.* ; Ziv-Agam, M.* ; Hagemann, T. ; Nono Nankam, P.A. ; Blüher, M. ; Liberty, I.F.* ; Dukhno, O.* ; Kukeev, I.* ; Yeger-Lotem, E.* ; Rudich, A.* ; Levin, L.*

sNucConv: A bulk RNA-seq deconvolution method trained on single-nucleus RNA-seq data to estimate cell-type composition of human adipose tissues.

iScience 27:110368 (2024)

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Deconvolution algorithms mostly rely on single-cell RNA-sequencing (scRNA-seq) data applied onto bulk RNA-sequencing (bulk RNA-seq) to estimate tissues’ cell-type composition, with performance accuracy validated on deposited databases. Adipose tissues’ cellular composition is highly variable, and adipocytes can only be captured by single-nucleus RNA-sequencing (snRNA-seq). Here we report the development of sNucConv, a Scaden deep-learning-based deconvolution tool, trained using 5 hSAT and 7 hVAT snRNA-seq-based data corrected by (i) snRNA-seq/bulk RNA-seq highly correlated genes and (ii) individual cell-type regression models. Applying sNucConv on our bulk RNA-seq data resulted in cell-type proportion estimation of 15 and 13 cell types, with accuracy of R = 0.93 (range: 0.76–0.97) and R = 0.95 (range: 0.92–0.98) for hVAT and hSAT, respectively. This performance level was further validated on an independent set of samples (5 hSAT; 5 hVAT). The resulting model was depot specific, reflecting depot differences in gene expression patterns. Jointly, sNucConv provides proof-of-concept for producing validated deconvolution models for tissues un-amenable to scRNA-seq.

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