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Temporal clustering analysis of endothelial cell gene expression following exposure to a conventional radiotherapy dose fraction using Gaussian process clustering

The vascular endothelium is considered as a key cell compartment for the response to ionizing radiation of normal tissues and tumors, and as a promising target to improve the differential effect of radiotherapy in the future. Following radiation exposure, the global endothelial cell response covers...

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Autores principales: Heinonen, Markus, Milliat, Fabien, Benadjaoud, Mohamed Amine, François, Agnès, Buard, Valérie, Tarlet, Georges, d’Alché-Buc, Florence, Guipaud, Olivier
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6169916/
https://www.ncbi.nlm.nih.gov/pubmed/30281653
http://dx.doi.org/10.1371/journal.pone.0204960
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author Heinonen, Markus
Milliat, Fabien
Benadjaoud, Mohamed Amine
François, Agnès
Buard, Valérie
Tarlet, Georges
d’Alché-Buc, Florence
Guipaud, Olivier
author_facet Heinonen, Markus
Milliat, Fabien
Benadjaoud, Mohamed Amine
François, Agnès
Buard, Valérie
Tarlet, Georges
d’Alché-Buc, Florence
Guipaud, Olivier
author_sort Heinonen, Markus
collection PubMed
description The vascular endothelium is considered as a key cell compartment for the response to ionizing radiation of normal tissues and tumors, and as a promising target to improve the differential effect of radiotherapy in the future. Following radiation exposure, the global endothelial cell response covers a wide range of gene, miRNA, protein and metabolite expression modifications. Changes occur at the transcriptional, translational and post-translational levels and impact cell phenotype as well as the microenvironment by the production and secretion of soluble factors such as reactive oxygen species, chemokines, cytokines and growth factors. These radiation-induced dynamic modifications of molecular networks may control the endothelial cell phenotype and govern recruitment of immune cells, stressing the importance of clearly understanding the mechanisms which underlie these temporal processes. A wide variety of time series data is commonly used in bioinformatics studies, including gene expression, protein concentrations and metabolomics data. The use of clustering of these data is still an unclear problem. Here, we introduce kernels between Gaussian processes modeling time series, and subsequently introduce a spectral clustering algorithm. We apply the methods to the study of human primary endothelial cells (HUVECs) exposed to a radiotherapy dose fraction (2 Gy). Time windows of differential expressions of 301 genes involved in key cellular processes such as angiogenesis, inflammation, apoptosis, immune response and protein kinase were determined from 12 hours to 3 weeks post-irradiation. Then, 43 temporal clusters corresponding to profiles of similar expressions, including 49 genes out of 301 initially measured, were generated according to the proposed method. Forty-seven transcription factors (TFs) responsible for the expression of clusters of genes were predicted from sequence regulatory elements using the MotifMap system. Their temporal profiles of occurrences were established and clustered. Dynamic network interactions and molecular pathways of TFs and differential genes were finally explored, revealing key node genes and putative important cellular processes involved in tissue infiltration by immune cells following exposure to a radiotherapy dose fraction.
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spelling pubmed-61699162018-10-19 Temporal clustering analysis of endothelial cell gene expression following exposure to a conventional radiotherapy dose fraction using Gaussian process clustering Heinonen, Markus Milliat, Fabien Benadjaoud, Mohamed Amine François, Agnès Buard, Valérie Tarlet, Georges d’Alché-Buc, Florence Guipaud, Olivier PLoS One Research Article The vascular endothelium is considered as a key cell compartment for the response to ionizing radiation of normal tissues and tumors, and as a promising target to improve the differential effect of radiotherapy in the future. Following radiation exposure, the global endothelial cell response covers a wide range of gene, miRNA, protein and metabolite expression modifications. Changes occur at the transcriptional, translational and post-translational levels and impact cell phenotype as well as the microenvironment by the production and secretion of soluble factors such as reactive oxygen species, chemokines, cytokines and growth factors. These radiation-induced dynamic modifications of molecular networks may control the endothelial cell phenotype and govern recruitment of immune cells, stressing the importance of clearly understanding the mechanisms which underlie these temporal processes. A wide variety of time series data is commonly used in bioinformatics studies, including gene expression, protein concentrations and metabolomics data. The use of clustering of these data is still an unclear problem. Here, we introduce kernels between Gaussian processes modeling time series, and subsequently introduce a spectral clustering algorithm. We apply the methods to the study of human primary endothelial cells (HUVECs) exposed to a radiotherapy dose fraction (2 Gy). Time windows of differential expressions of 301 genes involved in key cellular processes such as angiogenesis, inflammation, apoptosis, immune response and protein kinase were determined from 12 hours to 3 weeks post-irradiation. Then, 43 temporal clusters corresponding to profiles of similar expressions, including 49 genes out of 301 initially measured, were generated according to the proposed method. Forty-seven transcription factors (TFs) responsible for the expression of clusters of genes were predicted from sequence regulatory elements using the MotifMap system. Their temporal profiles of occurrences were established and clustered. Dynamic network interactions and molecular pathways of TFs and differential genes were finally explored, revealing key node genes and putative important cellular processes involved in tissue infiltration by immune cells following exposure to a radiotherapy dose fraction. Public Library of Science 2018-10-03 /pmc/articles/PMC6169916/ /pubmed/30281653 http://dx.doi.org/10.1371/journal.pone.0204960 Text en © 2018 Heinonen et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Heinonen, Markus
Milliat, Fabien
Benadjaoud, Mohamed Amine
François, Agnès
Buard, Valérie
Tarlet, Georges
d’Alché-Buc, Florence
Guipaud, Olivier
Temporal clustering analysis of endothelial cell gene expression following exposure to a conventional radiotherapy dose fraction using Gaussian process clustering
title Temporal clustering analysis of endothelial cell gene expression following exposure to a conventional radiotherapy dose fraction using Gaussian process clustering
title_full Temporal clustering analysis of endothelial cell gene expression following exposure to a conventional radiotherapy dose fraction using Gaussian process clustering
title_fullStr Temporal clustering analysis of endothelial cell gene expression following exposure to a conventional radiotherapy dose fraction using Gaussian process clustering
title_full_unstemmed Temporal clustering analysis of endothelial cell gene expression following exposure to a conventional radiotherapy dose fraction using Gaussian process clustering
title_short Temporal clustering analysis of endothelial cell gene expression following exposure to a conventional radiotherapy dose fraction using Gaussian process clustering
title_sort temporal clustering analysis of endothelial cell gene expression following exposure to a conventional radiotherapy dose fraction using gaussian process clustering
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6169916/
https://www.ncbi.nlm.nih.gov/pubmed/30281653
http://dx.doi.org/10.1371/journal.pone.0204960
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