Emergent genome-wide control in wildtype and genetically mutated lipopolysaccarides-stimulated macrophages.

Large-scale gene expression studies have mainly focused on highly expressed and 'discriminatory' genes to decipher key regulatory processes. Biological responses are consequence of the concerted action of gene regulatory network, thus, limiting our attention to genes having the most signif...

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Autores principales:	Masa Tsuchiya, Vincent Piras, Sangdun Choi, Shizuo Akira, Masaru Tomita, Alessandro Giuliani, Kumar Selvarajoo
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b1b0d1050428456480fff6c4ede195c0
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spelling	oai:doaj.org-article:b1b0d1050428456480fff6c4ede195c02021-11-25T06:16:35ZEmergent genome-wide control in wildtype and genetically mutated lipopolysaccarides-stimulated macrophages.1932-620310.1371/journal.pone.0004905https://doaj.org/article/b1b0d1050428456480fff6c4ede195c02009-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19300509/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Large-scale gene expression studies have mainly focused on highly expressed and 'discriminatory' genes to decipher key regulatory processes. Biological responses are consequence of the concerted action of gene regulatory network, thus, limiting our attention to genes having the most significant variations is insufficient for a thorough understanding of emergent whole genome response. Here we comprehensively analyzed the temporal oligonucleotide microarray data of lipopolysaccharide (LPS) stimulated macrophages in 4 genotypes; wildtype, Myeloid Differentiation factor 88 (MyD88) knockout (KO), TIR-domain-containing adapter-inducing interferon-beta (TRIF) KO and MyD88/TRIF double KO (DKO). Pearson correlations computed on the whole genome expression between different genotypes are extremely high (>0.98), indicating a strong co-regulation of the entire expression network. Further correlation analyses reveal genome-wide response is biphasic, i) acute-stochastic mode consisting of small number of sharply induced immune-related genes and ii) collective mode consisting of majority of weakly induced genes of diverse cellular processes which collectively adjust their expression level. Notably, temporal correlations of a small number of randomly selected genes from collective mode show scalability. Furthermore, in collective mode, the transition from large scatter in expression distributions for single ORFs to smooth linear lines emerges as an organizing principle when grouping of 50 ORFs and above. With this emergent behavior, the role of MyD88, TRIF and novel MyD88, TRIF-independent processes for gene induction can be linearly superposed to decipher quantitative whole genome differential control of transcriptional and mRNA decay machineries. Our work demonstrates genome-wide co-regulated responses subsequent to specific innate immune stimulus which have been largely neglected.Masa TsuchiyaVincent PirasSangdun ChoiShizuo AkiraMasaru TomitaAlessandro GiulianiKumar SelvarajooPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 3, p e4905 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Masa Tsuchiya Vincent Piras Sangdun Choi Shizuo Akira Masaru Tomita Alessandro Giuliani Kumar Selvarajoo Emergent genome-wide control in wildtype and genetically mutated lipopolysaccarides-stimulated macrophages.
description	Large-scale gene expression studies have mainly focused on highly expressed and 'discriminatory' genes to decipher key regulatory processes. Biological responses are consequence of the concerted action of gene regulatory network, thus, limiting our attention to genes having the most significant variations is insufficient for a thorough understanding of emergent whole genome response. Here we comprehensively analyzed the temporal oligonucleotide microarray data of lipopolysaccharide (LPS) stimulated macrophages in 4 genotypes; wildtype, Myeloid Differentiation factor 88 (MyD88) knockout (KO), TIR-domain-containing adapter-inducing interferon-beta (TRIF) KO and MyD88/TRIF double KO (DKO). Pearson correlations computed on the whole genome expression between different genotypes are extremely high (>0.98), indicating a strong co-regulation of the entire expression network. Further correlation analyses reveal genome-wide response is biphasic, i) acute-stochastic mode consisting of small number of sharply induced immune-related genes and ii) collective mode consisting of majority of weakly induced genes of diverse cellular processes which collectively adjust their expression level. Notably, temporal correlations of a small number of randomly selected genes from collective mode show scalability. Furthermore, in collective mode, the transition from large scatter in expression distributions for single ORFs to smooth linear lines emerges as an organizing principle when grouping of 50 ORFs and above. With this emergent behavior, the role of MyD88, TRIF and novel MyD88, TRIF-independent processes for gene induction can be linearly superposed to decipher quantitative whole genome differential control of transcriptional and mRNA decay machineries. Our work demonstrates genome-wide co-regulated responses subsequent to specific innate immune stimulus which have been largely neglected.
format	article
author	Masa Tsuchiya Vincent Piras Sangdun Choi Shizuo Akira Masaru Tomita Alessandro Giuliani Kumar Selvarajoo
author_facet	Masa Tsuchiya Vincent Piras Sangdun Choi Shizuo Akira Masaru Tomita Alessandro Giuliani Kumar Selvarajoo
author_sort	Masa Tsuchiya
title	Emergent genome-wide control in wildtype and genetically mutated lipopolysaccarides-stimulated macrophages.
title_short	Emergent genome-wide control in wildtype and genetically mutated lipopolysaccarides-stimulated macrophages.
title_full	Emergent genome-wide control in wildtype and genetically mutated lipopolysaccarides-stimulated macrophages.
title_fullStr	Emergent genome-wide control in wildtype and genetically mutated lipopolysaccarides-stimulated macrophages.
title_full_unstemmed	Emergent genome-wide control in wildtype and genetically mutated lipopolysaccarides-stimulated macrophages.
title_sort	emergent genome-wide control in wildtype and genetically mutated lipopolysaccarides-stimulated macrophages.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/b1b0d1050428456480fff6c4ede195c0
work_keys_str_mv	AT masatsuchiya emergentgenomewidecontrolinwildtypeandgeneticallymutatedlipopolysaccaridesstimulatedmacrophages AT vincentpiras emergentgenomewidecontrolinwildtypeandgeneticallymutatedlipopolysaccaridesstimulatedmacrophages AT sangdunchoi emergentgenomewidecontrolinwildtypeandgeneticallymutatedlipopolysaccaridesstimulatedmacrophages AT shizuoakira emergentgenomewidecontrolinwildtypeandgeneticallymutatedlipopolysaccaridesstimulatedmacrophages AT masarutomita emergentgenomewidecontrolinwildtypeandgeneticallymutatedlipopolysaccaridesstimulatedmacrophages AT alessandrogiuliani emergentgenomewidecontrolinwildtypeandgeneticallymutatedlipopolysaccaridesstimulatedmacrophages AT kumarselvarajoo emergentgenomewidecontrolinwildtypeandgeneticallymutatedlipopolysaccaridesstimulatedmacrophages
_version_	1718414003317768192

Emergent genome-wide control in wildtype and genetically mutated lipopolysaccarides-stimulated macrophages.

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