Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, USA.
Mol Syst Biol. 2010;6:349. doi: 10.1038/msb.2010.3. Epub 2010 Feb 16.
Sphingolipids including sphingosine-1-phosphate and ceramide participate in numerous cell programs through signaling mechanisms. This class of lipids has important functions in stress responses; however, determining which sphingolipid mediates specific events has remained encumbered by the numerous metabolic interconnections of sphingolipids, such that modulating a specific lipid of interest through manipulating metabolic enzymes causes 'ripple effects', which change levels of many other lipids. Here, we develop a method of integrative analysis for genomic, transcriptomic, and lipidomic data to address this previously intractable problem. This method revealed a specific signaling role for phytosphingosine-1-phosphate, a lipid with no previously defined specific function in yeast, in regulating genes required for mitochondrial respiration through the HAP complex transcription factor. This approach could be applied to extract meaningful biological information from a similar experimental design that produces multiple sets of high-throughput data.
鞘脂类物质包括鞘氨醇 1-磷酸和神经酰胺，通过信号机制参与众多细胞程序。这类脂质在应激反应中具有重要功能；然而，确定哪种鞘脂介导特定事件一直受到鞘脂代谢相互关系的困扰，以至于通过操纵代谢酶来调节特定感兴趣的脂质会产生“涟漪效应”，从而改变许多其他脂质的水平。在这里，我们开发了一种综合分析基因组、转录组和脂质组数据的方法来解决这个以前难以解决的问题。该方法揭示了植物鞘氨醇 1-磷酸的特定信号作用，植物鞘氨醇 1-磷酸是一种在酵母中没有先前定义的特定功能的脂质，通过 HAP 复合物转录因子调节线粒体呼吸所需的基因。这种方法可以应用于从产生多组高通量数据的类似实验设计中提取有意义的生物学信息。
