Zhou Yingyao, Ramachandran Vandana, Kumar Kota Arun, Westenberger Scott, Refour Phillippe, Zhou Bin, Li Fengwu, Young Jason A, Chen Kaisheng, Plouffe David, Henson Kerstin, Nussenzweig Victor, Carlton Jane, Vinetz Joseph M, Duraisingh Manoj T, Winzeler Elizabeth A
Genomics Institute of the Novartis Research Foundation, San Diego, California, USA.
PLoS One. 2008 Feb 13;3(2):e1570. doi: 10.1371/journal.pone.0001570.
A fundamental problem in systems biology and whole genome sequence analysis is how to infer functions for the many uncharacterized proteins that are identified, whether they are conserved across organisms of different phyla or are phylum-specific. This problem is especially acute in pathogens, such as malaria parasites, where genetic and biochemical investigations are likely to be more difficult. Here we perform comparative expression analysis on Plasmodium parasite life cycle data derived from P. falciparum blood, sporozoite, zygote and ookinete stages, and P. yoelii mosquito oocyst and salivary gland sporozoites, blood and liver stages and show that type II fatty acid biosynthesis genes are upregulated in liver and insect stages relative to asexual blood stages. We also show that some universally uncharacterized genes with orthologs in Plasmodium species, Saccharomyces cerevisiae and humans show coordinated transcription patterns in large collections of human and yeast expression data and that the function of the uncharacterized genes can sometimes be predicted based on the expression patterns across these diverse organisms. We also use a comprehensive and unbiased literature mining method to predict which uncharacterized parasite-specific genes are likely to have roles in processes such as gliding motility, host-cell interactions, sporozoite stage, or rhoptry function. These analyses, together with protein-protein interaction data, provide probabilistic models that predict the function of 926 uncharacterized malaria genes and also suggest that malaria parasites may provide a simple model system for the study of some human processes. These data also provide a foundation for further studies of transcriptional regulation in malaria parasites.
系统生物学和全基因组序列分析中的一个基本问题是如何推断众多已鉴定的未表征蛋白质的功能，无论它们是在不同门的生物中保守，还是特定于某个门。这个问题在病原体中尤为突出，比如疟原虫，在疟原虫中进行遗传和生化研究可能更困难。在这里，我们对来自恶性疟原虫血液、子孢子、合子和动合子阶段，以及约氏疟原虫蚊卵囊和唾液腺子孢子、血液和肝脏阶段的疟原虫生命周期数据进行了比较表达分析，结果表明，相对于无性血液阶段，II型脂肪酸生物合成基因在肝脏和昆虫阶段上调。我们还表明，一些在疟原虫物种、酿酒酵母和人类中具有直系同源物的普遍未表征基因，在大量人类和酵母表达数据中呈现出协调的转录模式，并且有时可以根据这些不同生物中的表达模式来预测未表征基因的功能。我们还使用了一种全面且无偏倚的文献挖掘方法，来预测哪些未表征的寄生虫特异性基因可能在诸如滑行运动、宿主细胞相互作用、子孢子阶段或棒状体功能等过程中发挥作用。这些分析，连同蛋白质 - 蛋白质相互作用数据，提供了概率模型，可预测926个未表征的疟疾基因的功能，还表明疟原虫可能为研究某些人类过程提供一个简单的模型系统。这些数据也为进一步研究疟原虫中的转录调控奠定了基础。
