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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 PLoS+One
2018 ; 13
(3
): e0193067
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Computational de novo discovery of distinguishing genes for biological processes
and cell types in complex tissues
#MMPMID29494600
Newberg LA
; Chen X
; Kodira CD
; Zavodszky MI
PLoS One
2018[]; 13
(3
): e0193067
PMID29494600
show ga
Bulk tissue samples examined by gene expression studies are usually
heterogeneous. The data gained from these samples display the confounding
patterns of mixtures consisting of multiple cell types or similar cell types in
various functional states, which hinders the elucidation of the molecular
mechanisms underlying complex biological phenomena. A realistic approach to
compensate for the limitations of experimentally separating homogenous cell
populations from mixed tissues is to computationally identify cell-type specific
patterns from bulk, heterogeneous measurements. We designed the CellDistinguisher
algorithm to analyze the gene expression data of mixed samples, identifying genes
that best distinguish biological processes and cell types. Coupled with a
deconvolution algorithm that takes cell type specific gene lists as input, we
show that CellDistinguisher performs as well as partial deconvolution algorithms
in predicting cell type composition without the need for prior knowledge of cell
type signatures. This approach is also better in predicting cell type signatures
than the one-step traditional complete deconvolution methods. To illustrate its
wide applicability, the algorithm was tested on multiple publicly available data
sets. In each case, CellDistinguisher identified genes reflecting biological
processes typical for the tissues and development stages of interest and
estimated the sample compositions accurately.