Statistical analysis of the processes controlling choline and ethanolamine glycerophospholipid molecular species composition.

The regulation and maintenance of the cellular lipidome through biosynthetic, remodeling, and catabolic mechanisms are critical for biological homeostasis during development, health and disease. These complex mechanisms control the architectures of lipid molecular species, which have diverse yet hig...

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Autores principales:	Kourosh Zarringhalam, Lu Zhang, Michael A Kiebish, Kui Yang, Xianlin Han, Richard W Gross, Jeffrey Chuang
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8af86a3295b048efa785f2dce5f4f2cd
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spelling	oai:doaj.org-article:8af86a3295b048efa785f2dce5f4f2cd2021-11-18T07:17:25ZStatistical analysis of the processes controlling choline and ethanolamine glycerophospholipid molecular species composition.1932-620310.1371/journal.pone.0037293https://doaj.org/article/8af86a3295b048efa785f2dce5f4f2cd2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22662143/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The regulation and maintenance of the cellular lipidome through biosynthetic, remodeling, and catabolic mechanisms are critical for biological homeostasis during development, health and disease. These complex mechanisms control the architectures of lipid molecular species, which have diverse yet highly regulated fatty acid chains at both the sn1 and sn2 positions. Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) serve as the predominant biophysical scaffolds in membranes, acting as reservoirs for potent lipid signals and regulating numerous enzymatic processes. Here we report the first rigorous computational dissection of the mechanisms influencing PC and PE molecular architectures from high-throughput shotgun lipidomic data. Using novel statistical approaches, we have analyzed multidimensional mass spectrometry-based shotgun lipidomic data from developmental mouse heart and mature mouse heart, lung, brain, and liver tissues. We show that in PC and PE, sn1 and sn2 positions are largely independent, though for low abundance species regulatory processes may interact with both the sn1 and sn2 chain simultaneously, leading to cooperative effects. Chains with similar biochemical properties appear to be remodeled similarly. We also see that sn2 positions are more regulated than sn1, and that PC exhibits stronger cooperative effects than PE. A key aspect of our work is a novel statistically rigorous approach to determine cooperativity based on a modified Fisher's exact test using Markov Chain Monte Carlo sampling. This computational approach provides a novel tool for developing mechanistic insight into lipidomic regulation.Kourosh ZarringhalamLu ZhangMichael A KiebishKui YangXianlin HanRichard W GrossJeffrey ChuangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 5, p e37293 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kourosh Zarringhalam Lu Zhang Michael A Kiebish Kui Yang Xianlin Han Richard W Gross Jeffrey Chuang Statistical analysis of the processes controlling choline and ethanolamine glycerophospholipid molecular species composition.
description	The regulation and maintenance of the cellular lipidome through biosynthetic, remodeling, and catabolic mechanisms are critical for biological homeostasis during development, health and disease. These complex mechanisms control the architectures of lipid molecular species, which have diverse yet highly regulated fatty acid chains at both the sn1 and sn2 positions. Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) serve as the predominant biophysical scaffolds in membranes, acting as reservoirs for potent lipid signals and regulating numerous enzymatic processes. Here we report the first rigorous computational dissection of the mechanisms influencing PC and PE molecular architectures from high-throughput shotgun lipidomic data. Using novel statistical approaches, we have analyzed multidimensional mass spectrometry-based shotgun lipidomic data from developmental mouse heart and mature mouse heart, lung, brain, and liver tissues. We show that in PC and PE, sn1 and sn2 positions are largely independent, though for low abundance species regulatory processes may interact with both the sn1 and sn2 chain simultaneously, leading to cooperative effects. Chains with similar biochemical properties appear to be remodeled similarly. We also see that sn2 positions are more regulated than sn1, and that PC exhibits stronger cooperative effects than PE. A key aspect of our work is a novel statistically rigorous approach to determine cooperativity based on a modified Fisher's exact test using Markov Chain Monte Carlo sampling. This computational approach provides a novel tool for developing mechanistic insight into lipidomic regulation.
format	article
author	Kourosh Zarringhalam Lu Zhang Michael A Kiebish Kui Yang Xianlin Han Richard W Gross Jeffrey Chuang
author_facet	Kourosh Zarringhalam Lu Zhang Michael A Kiebish Kui Yang Xianlin Han Richard W Gross Jeffrey Chuang
author_sort	Kourosh Zarringhalam
title	Statistical analysis of the processes controlling choline and ethanolamine glycerophospholipid molecular species composition.
title_short	Statistical analysis of the processes controlling choline and ethanolamine glycerophospholipid molecular species composition.
title_full	Statistical analysis of the processes controlling choline and ethanolamine glycerophospholipid molecular species composition.
title_fullStr	Statistical analysis of the processes controlling choline and ethanolamine glycerophospholipid molecular species composition.
title_full_unstemmed	Statistical analysis of the processes controlling choline and ethanolamine glycerophospholipid molecular species composition.
title_sort	statistical analysis of the processes controlling choline and ethanolamine glycerophospholipid molecular species composition.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/8af86a3295b048efa785f2dce5f4f2cd
work_keys_str_mv	AT kouroshzarringhalam statisticalanalysisoftheprocessescontrollingcholineandethanolamineglycerophospholipidmolecularspeciescomposition AT luzhang statisticalanalysisoftheprocessescontrollingcholineandethanolamineglycerophospholipidmolecularspeciescomposition AT michaelakiebish statisticalanalysisoftheprocessescontrollingcholineandethanolamineglycerophospholipidmolecularspeciescomposition AT kuiyang statisticalanalysisoftheprocessescontrollingcholineandethanolamineglycerophospholipidmolecularspeciescomposition AT xianlinhan statisticalanalysisoftheprocessescontrollingcholineandethanolamineglycerophospholipidmolecularspeciescomposition AT richardwgross statisticalanalysisoftheprocessescontrollingcholineandethanolamineglycerophospholipidmolecularspeciescomposition AT jeffreychuang statisticalanalysisoftheprocessescontrollingcholineandethanolamineglycerophospholipidmolecularspeciescomposition
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Statistical analysis of the processes controlling choline and ethanolamine glycerophospholipid molecular species composition.

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