研究人员努力探索扩大功能景观的人类基因组
国家人类基因组研究所(NHGRI),国立卫生研究院(NIH)的一部分,宣布拨款总额超过8000万美元在未来四年扩大DNA序列元素的百科全书(编码)项目,在试点阶段取得了挑衅的新洞察人类基因组的组织和功能。
“基于编码的早期成功,我们推进全面倡议建立一个生物学上的零件清单的功能元素在人类基因组中,“弗朗西斯•s•科林斯美国国家人类基因组研究所主任说,医学博士博士。
“编码试点,看着只有1%的人类基因蓝图,产生结果,正在改变着许多关于我们的基因组的一个长久观点。编码的努力调查整个基因组将发现更令人兴奋惊喜,给我们提供一个更完整的人类健康与疾病的生物学基础,”柯林斯说。
今年6月,编码研究财团一系列里程碑式的论文发表在期刊“自然”和“基因组研究”,找到了组织,功能和基因组的进化比大多数人怀疑复杂得多。
“我们学到了很多有价值的教训编码试点项目。其中科学团队合作的重要性,”爱丽丝a·法因戈尔德博士说,项目主任NHGRI的部门编码单位以外的研究。“飞行员的强大的多学科协作的例子后,我们相信,比例增大的编码团队将成功在寻求建立一个全面的目录组件人类基因组生物功能的关键。”
除了研究经费支持编码项目的扩张,NHGRI今天还宣布奖项两半工业规模的项目,一个编码数据协调中心,六个项目开发新方法和技术旨在帮助编码项目实现其目标。
主要调查人员选择接收编码扩大资助:
布拉德利•伯恩斯坦,医学博士博士;广泛的麻省理工学院和哈佛、剑桥、质量。480万美元(四年);“高通量测序的染色质监管元素。”Utilizing the technique of chromatin immunoprecipitation followed by high-throughput DNA sequencing, this team will map modifications of histones in various types of human cells. Histones are proteins that play a key role in DNA packaging.
克劳福德•格里高利博士;杜克大学基因组科学与政策研究所,达勒姆,N, c;650万美元(四年);“全面的识别活跃在人类染色质功能元素。”These researchers will seek to identify and characterize regions of open chromatin through DNase I hypersensitivity assays, formaldehyde-assisted isolation of regulatory elements and chromatin immunoprecipitation for a few key DNA-binding factors. Chromatin is the complex of DNA and proteins that makes up chromosomes.
•托马斯Gingeras博士;Affymetrix Inc .,加州圣克拉拉。1020万美元(四年);“全面描述和分类的人类转录组。”This group will identify protein-coding and non-protein-coding ribonucleic acid (RNA) transcripts using microarrays, high-throughput sequencing, sequenced paired-end ditags and sequenced cap analysis of gene expression tags. RNA is an information molecule vital to a number of biological functions, including protein production.
蒂姆•哈伯德博士;维尔康姆基金会桑格研究所,英国Hinxton;850万美元(四年);“综合人类基因组注释:一代的参考基因集。”Using computational methods, manual annotation and targeted experiments, this team will annotate gene features in the human genome. Such features include genes that code for proteins; genes that are transcribed, but do not code for proteins; and pseudogenes, which are DNA sequences similar to normal genes, but which have been altered slightly so they are not functional.
•理查德•迈尔斯博士;斯坦福大学,斯坦福大学,加州。1460万美元(四年);“全球监管元素在人类基因组的注释。”This group has two goals: to identify transcription factor binding sites by using chromatin immunoprecipitation followed by high-throughput sequencing, and to pilot the use of high-throughput sequencing to determine the methylation status of CpG-rich regions of the human genome. Transcription factors are proteins and enzymes that initiate the transcription of a gene's DNA sequence into RNA. Methylation refers to a specific chemical modification of DNA, which can silence or reduce the activity of the affected region of DNA.
•迈克尔•斯奈德博士;耶鲁大学纽黑文,康涅狄格州1150万美元(四年);“生产中心的全球监管元素的映射。These researchers will identify transcription factor binding sites in the human genome using chromatin immunoprecipitation, followed by high-throughput sequencing.
•约翰•Stamatoyannopoulos医学博士;华盛顿大学西雅图分校的;970万美元(四年);“人类DNase我高度敏感的综合目录网站。”This team will map and functionally classify DNase I hypersensitive sites across major human cell lineages. It will do this using digital DNase I and histone modification mapping by high-throughput sequencing. DNAse I is an enzyme that cleaves DNA at sites where it is exposed by regulatory proteins. DNase I hypersensitive sites mark the location of regulatory elements in the human genome. team will map and classify DNase I hypersensitive sites in open chromatin using microarrays, high-throughput sequencing and the polymerase chain reaction. DNAse I is an enzyme that cleaves DNA at exposed sites.
主要调查人员选择接收编码半工业规模授予:
•斯科特•特南鲍姆博士;纽约大学Albany-State大学,220万美元(三年);“全面的识别编码RNA-based,顺式元素。”In this pilot project, researchers will strive to identify sites that are targets for RNA-binding proteins through immunoprecipitation coupled with microarrays and high-throughput sequencing.
•挚萍翁博士;波士顿大学;150万美元(三年);“人类启动子转录因子结合网站的识别。”This pilot project will aim to computationally predict transcription factor binding sites that determine the activities of promoters. Promoters are regions of DNA that serve as binding sites for proteins that guide the initiation of transcription of genes.
编码的数据协调中心将由:
詹姆斯•w•肯特博士;加州大学圣克鲁斯分校;500万美元(四年);“UCSC的编码数据协调中心”。This group will collect, organize, store, manage and provide access to data from ENCODE and related projects.
主要调查人员选择接收技术发展资助:
•霍华德Chang医学博士博士;斯坦福大学,斯坦福大学,加州。130万美元(三年);“在RNA结构图案。”These researchers will develop high-throughput methods to predict functional motifs in RNA, to map RNA structure and to assign biological functions to RNA motifs.
•迈克尔•杜斯纳博士;华盛顿大学西雅图分校的;110万美元(三年);通过单分子测序”高清体内的碳足迹。”This group's goal is to develop an in vivo method that utilizes single molecule sequencing to identify sites of protein-DNA interaction by differential cleavage sensitivity with ultraviolet light, dimethylsulfate and DNase I.
约翰•Greally博士;纽约爱因斯坦医学院的,布朗克斯;150万美元(三年);“表观基因组的大规模并行测序技术。”This team will work to develop high-throughput sequencing methods to analyze methylation of cytosine and to map histone modifications.
李•奢靡,博士;印第安纳波利斯印第安纳大学;870000美元(三年);“发现在人类基因组中基因工程模块。”This team will strive to develop computational methods for identifying conserved cis-regulatory modules in non-protein coding regions of the human genome.
•马塞洛Nobrega,医学博士博士;芝加哥大学;150万美元(三年);”体内生成和验证基因在真核基因组地图。”The two goals of this group are: to develop tagged DNA binding proteins that are recognizable by tag-specific antibodies for use in mapping binding sites for a wide range of proteins, and to develop platforms to test predicted enhancers, silencers and insulators in the human genome.
•皮阮博士;新加坡基因组研究所;990000美元(三年);“全基因组染色质交互分析使用Paired-End diTagging。”This team will develop methods to characterize long-range chromatin interactions involved in transcription using high-throughput sequencing.
