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美国启动数据与知识重大基础设施建设计划 快报文章
地球科学快报,2023年第07期
作者:  张树良
Microsoft Word(16Kb)  |  收藏  |  浏览/下载:572/0  |  提交时间:2023/04/10
Proto-OKN  data and knowledge infrastructure  NSF  
欧洲环境署-欧洲环境信息与观测网络2021—2030年战略 快报文章
资源环境快报,2021年第3期
作者:  刘莉娜
Microsoft Word(18Kb)  |  收藏  |  浏览/下载:481/0  |  提交时间:2021/02/15
Data and Knowledge  Environment  Climate  
A metabolic pathway for bile acid dehydroxylation by the gut microbiome 期刊论文
NATURE, 2020
作者:  Zhong, Miao;  Tran, Kevin;  Min, Yimeng;  Wang, Chuanhao;  Wang, Ziyun;  Dinh, Cao-Thang;  De Luna, Phil;  Yu, Zongqian;  Rasouli, Armin Sedighian;  Brodersen, Peter;  Sun, Song;  Voznyy, Oleksandr;  Tan, Chih-Shan;  Askerka, Mikhail;  Che, Fanglin;  Liu, Min;  Seifitokaldani, Ali;  Pang, Yuanjie;  Lo, Shen-Chuan;  Ip, Alexander;  Ulissi, Zachary;  Sargent, Edward H.
收藏  |  浏览/下载:15/0  |  提交时间:2020/07/03

The biosynthetic pathway that produces the secondary bile acids DCA and LCA in human gut microbes has been fully characterized, engineered into another bacterial host, and used to confer DCA production in germ-free mice-an important proof-of-principle for the engineering of gut microbial pathways.


The gut microbiota synthesize hundreds of molecules, many of which influence host physiology. Among the most abundant metabolites are the secondary bile acids deoxycholic acid (DCA) and lithocholic acid (LCA), which accumulate at concentrations of around 500 mu M and are known to block the growth ofClostridium difficile(1), promote hepatocellular carcinoma(2)and modulate host metabolism via the G-protein-coupled receptor TGR5 (ref.(3)). More broadly, DCA, LCA and their derivatives are major components of the recirculating pool of bile acids(4)  the size and composition of this pool are a target of therapies for primary biliary cholangitis and nonalcoholic steatohepatitis. Nonetheless, despite the clear impact of DCA and LCA on host physiology, an incomplete knowledge of their biosynthetic genes and a lack of genetic tools to enable modification of their native microbial producers limit our ability to modulate secondary bile acid levels in the host. Here we complete the pathway to DCA and LCA by assigning and characterizing enzymes for each of the steps in its reductive arm, revealing a strategy in which the A-B rings of the steroid core are transiently converted into an electron acceptor for two reductive steps carried out by Fe-S flavoenzymes. Using anaerobic in vitro reconstitution, we establish that a set of six enzymes is necessary and sufficient for the eight-step conversion of cholic acid to DCA. We then engineer the pathway intoClostridium sporogenes, conferring production of DCA and LCA on a nonproducing commensal and demonstrating that a microbiome-derived pathway can be expressed and controlled heterologously. These data establish a complete pathway to two central components of the bile acid pool.


  
Variability in the analysis of a single neuroimaging dataset by many teams 期刊论文
NATURE, 2020
作者:  Liu, Jifeng;  Soria, Roberto;  Zheng, Zheng;  Zhang, Haotong;  Lu, Youjun;  Wang, Song;  Yuan, Hailong
收藏  |  浏览/下载:23/0  |  提交时间:2020/07/03

Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses(1). The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset(2-5). Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed.


The results obtained by seventy different teams analysing the same functional magnetic resonance imaging dataset show substantial variation, highlighting the influence of analytical choices and the importance of sharing workflows publicly and performing multiple analyses.


  
Ancient West African foragers in the context of African population history 期刊论文
NATURE, 2020, 577 (7792) : 665-+
作者:  Grunwald, Hannah A.;  Gantz, Valentino M.;  Poplawski, Gunnar;  Xu, Xiang-Ru S.;  Bier, Ethan;  Cooper, Kimberly L.
收藏  |  浏览/下载:24/0  |  提交时间:2020/07/03

Genome-wide ancestry profiles of four individuals, dating to 8,000 and 3,000 years before present, from the archaeological site of Shum Laka (Cameroon) shed light on the deep population history of sub-Saharan Africa.


Our knowledge of ancient human population structure in sub-Saharan Africa, particularly prior to the advent of food production, remains limited. Here we report genome-wide DNA data from four children-two of whom were buried approximately 8,000 years ago and two 3,000 years ago-from Shum Laka (Cameroon), one of the earliest known archaeological sites within the probable homeland of the Bantu language group(1-11). One individual carried the deeply divergent Y chromosome haplogroup A00, which today is found almost exclusively in the same region(12,13). However, the genome-wide ancestry profiles of all four individuals are most similar to those of present-day hunter-gatherers from western Central Africa, which implies that populations in western Cameroon today-as well as speakers of Bantu languages from across the continent-are not descended substantially from the population represented by these four people. We infer an Africa-wide phylogeny that features widespread admixture and three prominent radiations, including one that gave rise to at least four major lineages deep in the history of modern humans.


  
Genomic basis for RNA alterations in cancer 期刊论文
NATURE, 2020, 578 (7793) : 129-+
作者:  Petitprez, Florent;  39;han
收藏  |  浏览/下载:17/0  |  提交时间:2020/07/03

Transcript alterations often result from somatic changes in cancer genomes(1). Various forms of RNA alterations have been described in cancer, including overexpression(2), altered splicing(3) and gene fusions(4)  however, it is difficult to attribute these to underlying genomic changes owing to heterogeneity among patients and tumour types, and the relatively small cohorts of patients for whom samples have been analysed by both transcriptome and whole-genome sequencing. Here we present, to our knowledge, the most comprehensive catalogue of cancer-associated gene alterations to date, obtained by characterizing tumour transcriptomes from 1,188 donors of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)(5). Using matched whole-genome sequencing data, we associated several categories of RNA alterations with germline and somatic DNA alterations, and identified probable genetic mechanisms. Somatic copy-number alterations were the major drivers of variations in total gene and allele-specific expression. We identified 649 associations of somatic single-nucleotide variants with gene expression in cis, of which 68.4% involved associations with flanking non-coding regions of the gene. We found 1,900 splicing alterations associated with somatic mutations, including the formation of exons within introns in proximity to Alu elements. In addition, 82% of gene fusions were associated with structural variants, including 75 of a new class, termed '  bridged'  fusions, in which a third genomic location bridges two genes. We observed transcriptomic alteration signatures that differ between cancer types and have associations with variations in DNA mutational signatures. This compendium of RNA alterations in the genomic context provides a rich resource for identifying genes and mechanisms that are functionally implicated in cancer.


  
Giant virus diversity and host interactions through global metagenomics 期刊论文
NATURE, 2020: 1-+
作者:  Su, Jie;  Morgani, Sophie M.;  David, Charles J.;  Wang, Qiong;  Er, Ekrem Emrah;  Huang, Yun-Han;  Basnet, Harihar;  Zou, Yilong;  Shu, Weiping;  Soni, Rajesh K.;  Hendrickson, Ronald C.;  Hadjantonakis, Anna-Katerina;  Massague, Joan
收藏  |  浏览/下载:21/0  |  提交时间:2020/07/03

Analysis of metagenomics data revealed that large and giant viruses are globally widely distributed and are associated with most major eukaryotic lineages.


Our current knowledge about nucleocytoplasmic large DNA viruses (NCLDVs) is largely derived from viral isolates that are co-cultivated with protists and algae. Here we reconstructed 2,074 NCLDV genomes from sampling sites across the globe by building on the rapidly increasing amount of publicly available metagenome data. This led to an 11-fold increase in phylogenetic diversity and a parallel 10-fold expansion in functional diversity. Analysis of 58,023 major capsid proteins from large and giant viruses using metagenomic data revealed the global distribution patterns and cosmopolitan nature of these viruses. The discovered viral genomes encoded a wide range of proteins with putative roles in photosynthesis and diverse substrate transport processes, indicating that host reprogramming is probably a common strategy in the NCLDVs. Furthermore, inferences of horizontal gene transfer connected viral lineages to diverse eukaryotic hosts. We anticipate that the global diversity of NCLDVs that we describe here will establish giant viruses-which are associated with most major eukaryotic lineages-as important players in ecosystems across Earth'  s biomes.


  
The UK's largest UK University Fair for International Students 会议
London, United Kingdom, 会议类型: Exhibition, 2017