A deep sequencing approach to comparatively analyze the transcriptome of lifecycle stages of the filarial worm, Brugia malayi.
A deep sequencing approach to comparatively analyze the transcriptome of lifecycle stages of the filarial worm, Brugia malayi.
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DOI：
10.1371/journal.pntd.0001409
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发表时间：
2011-12
影响因子：
3.8
通讯作者：
Michalski ML
中科院分区：
文献类型：
--
作者：
Choi YJ;Ghedin E;Berriman M;McQuillan J;Holroyd N;Mayhew GF;Christensen BM;Michalski ML
制定防治寄生线虫的干预战略仍然是一项重大挑战。基因组和后基因组方法在提供有关这些寄生虫的基本分子信息方面发挥着越来越重要的作用，从而加强了基础和转化研究。在这里，我们报告了一个全面的全基因组调查的人类丝虫寄生虫马来丝虫的发育转录组。使用深度测序，我们分析了卵和胚胎、未成熟（≤3日龄）和成熟微丝蚴（MF）、第三和第四期幼虫（L3和L4）以及成年雄性和雌性蠕虫的转录组。跨这些阶段的比较分析提供了定义和区分寄生虫不同生命周期阶段的分子库的详细概述。全基因组评估的整体转录变异表明，角质层胶原蛋白家族和那些涉及蜕皮表现出显着的动态阶段依赖性模式。特别令人感兴趣的是，由于其潜在的参与生殖过程的基因显示性别偏见或种系富集的配置文件的识别。该研究还揭示了幼虫发育过程中的离散转录变化，即伴随MF成熟和L3至L4转变的那些变化，这些变化分别在蚊子载体和脊椎动物宿主中建立成功感染至关重要。寄生虫生命周期的转录程序的表征是理解感染周期所需的发育过程的重要一步。我们发现，转录程序有一些特定的阶段在蠕虫发育过程中激活的途径。除了推进我们对转录组动力学的理解，这些数据将有助于通过促进新的转录元件和剪接变体的鉴定来研究基因组结构和组织。淋巴丝虫病，也被称为象皮病，是一种热带疾病，影响全世界超过1.2亿人。超过4000万人生活在痛苦、毁容的症状中，这些症状可能导致严重的虚弱和社会耻辱。这种疾病是由线状丝虫（蛔虫）感染引起的，这种线虫具有复杂的寄生生命周期，涉及人类和蚊子宿主。在这项研究中，作者使用深度测序技术分析了人类丝虫马来丝虫在不同生命周期阶段的转录组（转录成信使RNA的基因组，而不是基因组中的所有基因）。分析揭示了从卵到幼虫阶段到成虫的RNA表达的主要转变。使用统计方法，作者确定了具有不同生命阶段依赖转录模式的基因组，特别强调显示性别偏见或种系富集模式的基因以及在幼虫发育过程中显示显着变化的基因。本研究首次全面分析了B的生命周期转录组。马来语，提供了基本的分子信息，可以帮助研究人员更好地了解寄生虫生物学，并为开发更有效的干预措施提供线索。
Developing intervention strategies for the control of parasitic nematodes continues to be a significant challenge. Genomic and post-genomic approaches play an increasingly important role for providing fundamental molecular information about these parasites, thus enhancing basic as well as translational research. Here we report a comprehensive genome-wide survey of the developmental transcriptome of the human filarial parasite Brugia malayi. Using deep sequencing, we profiled the transcriptome of eggs and embryos, immature (≤3 days of age) and mature microfilariae (MF), third- and fourth-stage larvae (L3 and L4), and adult male and female worms. Comparative analysis across these stages provided a detailed overview of the molecular repertoires that define and differentiate distinct lifecycle stages of the parasite. Genome-wide assessment of the overall transcriptional variability indicated that the cuticle collagen family and those implicated in molting exhibit noticeably dynamic stage-dependent patterns. Of particular interest was the identification of genes displaying sex-biased or germline-enriched profiles due to their potential involvement in reproductive processes. The study also revealed discrete transcriptional changes during larval development, namely those accompanying the maturation of MF and the L3 to L4 transition that are vital in establishing successful infection in mosquito vectors and vertebrate hosts, respectively. Characterization of the transcriptional program of the parasite's lifecycle is an important step toward understanding the developmental processes required for the infectious cycle. We find that the transcriptional program has a number of stage-specific pathways activated during worm development. In addition to advancing our understanding of transcriptome dynamics, these data will aid in the study of genome structure and organization by facilitating the identification of novel transcribed elements and splice variants. Lymphatic filariasis, also known as elephantiasis, is a tropical disease affecting over 120 million people worldwide. More than 40 million people live with painful, disfiguring symptoms that can cause severe debilitation and social stigma. The disease is caused by infection with thread-like filarial nematodes (roundworms) that have a complex parasitic lifecycle involving both human and mosquito hosts. In the study, the authors profiled the transcriptome (the set of genes transcribed into messenger RNA rather than all of those in the genome) of the human filarial worm Brugia malayi in different lifecyle stages using deep sequencing technology. The analysis revealed major transitions in RNA expression from eggs through larval stages to adults. Using statistical approaches, the authors identified groups of genes with distinct life stage dependent transcriptional patterns, with particular emphasis on genes displaying sex-biased or germline-enriched patterns and those displaying significant changes during larval development. This study presents a first comprehensive analysis of the lifecycle transcriptome of B. malayi, providing fundamental molecular information that should help researchers better understand parasite biology and could provide clues for the development of more effective interventions.
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影响因子：
2.1
作者：
Chirgwin, Sharon R.;Coleman, Sharon U.;Klei, Thomas R.
通讯作者：
Klei, Thomas R.
影响因子：
1.6
作者：
DEHOLLANDA, JC;DENHAM, DA;SUSWILLO, RR
通讯作者：
SUSWILLO, RR
影响因子：
2.7
作者：
Koehler, Heinz-R.;Kloas, Werner;Schoenfelder, Gilbert
通讯作者：
Schoenfelder, Gilbert
影响因子：
2.9
作者：
CHOMCZYNSKI, P;SACCHI, N
通讯作者：
SACCHI, N
DOI：
10.1073/pnas.1011481108
发表时间：
2011-06-07
影响因子：
11.1
作者：
Bennuru, Sasisekhar;Meng, Zhaojing;Nutman, Thomas B.
通讯作者：
Nutman, Thomas B.