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  • Three-dimensional map of nonhematopoietic bone and bone-marrow cells and molecules
    Nat. Biotechnol. (IF 41.667) Pub Date : 
    Daniel L Coutu, Konstantinos D Kokkaliaris, Leo Kunz, Timm Schroeder

    Three-dimensional map of nonhematopoietic bone and bone-marrow cells and molecules Three-dimensional map of nonhematopoietic bone and bone-marrow cells and molecules, Published online: 13 November 2017; doi:10.1038/nbt.4006 NatureArticleSnippet(type=short-summary, markup= A compendium detailing the localization of bone and bone-marrow-microenvironment cells and proteins will enable efforts to understand the functions of this niche. , isJats=true)

    更新日期:2017-11-13
  • Accurate assembly of transcripts through phase-preserving graph decomposition
    Nat. Biotechnol. (IF 41.667) Pub Date : 
    Mingfu Shao, Carl Kingsford

    Accurate assembly of transcripts through phase-preserving graph decomposition Accurate assembly of transcripts through phase-preserving graph decomposition, Published online: 13 November 2017; doi:10.1038/nbt.4020 NatureArticleSnippet(type=short-summary, markup= Scallop improves identification of multi-exon and transcripts expressed at low levels by retaining phasing information during assembly. , isJats=true)

    更新日期:2017-11-13
  • Structure-guided chemical modification of guide RNA enables potent non-viral in vivo genome editing
    Nat. Biotechnol. (IF 41.667) Pub Date : 2017-11-13
    Hao Yin, Chun-Qing Song, Sneha Suresh, Qiongqiong Wu, Stephen Walsh, Luke Hyunsik Rhym, Esther Mintzer, Mehmet Fatih Bolukbasi, Lihua Julie Zhu, Kevin Kauffman, Haiwei Mou, Alicia Oberholzer, Junmei Ding, Suet-Yan Kwan, Roman L Bogorad, Timofei Zatsepin, Victor Koteliansky, Scot A Wolfe, Wen Xue, Robert Langer, Daniel G Anderson

    Structure-guided chemical modification of guide RNA enables potent non-viral in vivo genome editing Structure-guided chemical modification of guide RNA enables potent non-viral in vivo genome editing, Published online: 13 November 2017; doi:10.1038/nbt.4005 NatureArticleSnippet(type=short-summary, markup= Efficient Cas9 genome editing in vivo is achieved without viral vectors using chemically modified single-guide RNAs. , isJats=true)

    更新日期:2017-11-13
  • Three-dimensional map of nonhematopoietic bone and bone-marrow cells and molecules
    Nat. Biotechnol. (IF 41.667) Pub Date : 
    Daniel L Coutu, Konstantinos D Kokkaliaris, Leo Kunz, Timm Schroeder

    Three-dimensional map of nonhematopoietic bone and bone-marrow cells and molecules Three-dimensional map of nonhematopoietic bone and bone-marrow cells and molecules, Published online: 13 November 2017; doi:10.1038/nbt.4006 NatureArticleSnippet(type=short-summary, markup= A compendium detailing the localization of bone and bone-marrow-microenvironment cells and proteins will enable efforts to understand the functions of this niche. , isJats=true)

    更新日期:2017-11-13
  • Accurate assembly of transcripts through phase-preserving graph decomposition
    Nat. Biotechnol. (IF 41.667) Pub Date : 2017-11-13
    Mingfu Shao, Carl Kingsford

    Accurate assembly of transcripts through phase-preserving graph decomposition Accurate assembly of transcripts through phase-preserving graph decomposition, Published online: 13 November 2017; doi:10.1038/nbt.4020 NatureArticleSnippet(type=short-summary, markup= Scallop improves identification of multi-exon and transcripts expressed at low levels by retaining phasing information during assembly. , isJats=true)

    更新日期:2017-11-13
  • Structure-guided chemical modification of guide RNA enables potent non-viral in vivo genome editing
    Nat. Biotechnol. (IF 41.667) Pub Date : 2017-11-13
    Hao Yin, Chun-Qing Song, Sneha Suresh, Qiongqiong Wu, Stephen Walsh, Luke Hyunsik Rhym, Esther Mintzer, Mehmet Fatih Bolukbasi, Lihua Julie Zhu, Kevin Kauffman, Haiwei Mou, Alicia Oberholzer, Junmei Ding, Suet-Yan Kwan, Roman L Bogorad, Timofei Zatsepin, Victor Koteliansky, Scot A Wolfe, Wen Xue, Robert Langer, Daniel G Anderson

    Structure-guided chemical modification of guide RNA enables potent non-viral in vivo genome editing Structure-guided chemical modification of guide RNA enables potent non-viral in vivo genome editing, Published online: 13 November 2017; doi:10.1038/nbt.4005 NatureArticleSnippet(type=short-summary, markup= Efficient Cas9 genome editing in vivo is achieved without viral vectors using chemically modified single-guide RNAs. , isJats=true)

    更新日期:2017-11-13
  • Duchenne drug clings on for FDA nod
    Nat. Biotechnol. (IF 41.667) Pub Date : 2017-11-09

    Duchenne drug clings on for FDA nodDuchenne drug clings on for FDA nod, Published online: 09 November 2017; doi:10.1038/nbt1117-999

    更新日期:2017-11-10
  • Ethical principles for the use of human cellular biotechnologies
    Nat. Biotechnol. (IF 41.667) Pub Date : 2017-11-09
    Paul Root Wolpe, Karen S Rommelfanger, the Drafting and Reviewing Delegates of the BEINGS Working Groups

    Ethical principles for the use of human cellular biotechnologiesEthical principles for the use of human cellular biotechnologies, Published online: 09 November 2017; doi:10.1038/nbt.4007NatureArticleSnippet(type=standfirst, markup=Recent developments in bioengineering promise the possibility of new diagnostic and treatment strategies, novel industrial processes, and innovative approaches to thorny problems in fields such as nutrition, agriculture, and biomanufacturing. As modern genetics has matured and developed technologies of increasing power, debates over risk assessments and proper applications of the technology, and over who should have decision-making power over such issues, have become more prominent. Recently, some scientists have advocated that ethicists “step out of the way,” whereas others have called for greater ethical scrutiny, or even for moratoria on some lines of research. As a community, however, we must together determine the proper application of these powerful biological tools. This paper, a consensus statement of a group of interdisciplinary delegates drawn from the top biotech-producing countries of the world, offers a set of ethical principles to contribute to the ethical conversation about human cellular biotechnological research moving forward., isJats=true)

    更新日期:2017-11-10
  • Spanish group defeats Shkreli in Chagas voucher race
    Nat. Biotechnol. (IF 41.667) Pub Date : 2017-11-09
    Lisa Melton

    Spanish group defeats Shkreli in Chagas voucher raceSpanish group defeats Shkreli in Chagas voucher race, Published online: 09 November 2017; doi:10.1038/nbt1117-1003

    更新日期:2017-11-10
  • First rounders: Stelios Papadopoulos
    Nat. Biotechnol. (IF 41.667) Pub Date : 2017-11-09

    First rounders: Stelios PapadopoulosFirst rounders: Stelios Papadopoulos, Published online: 09 November 2017; doi:10.1038/nbt.3995

    更新日期:2017-11-10
  • Public views on gene editing and its uses
    Nat. Biotechnol. (IF 41.667) Pub Date : 2017-11-09
    George Gaskell, Imre Bard, Agnes Allansdottir, Rui Vieira da Cunha, Peter Eduard, Juergen Hampel, Elisabeth Hildt, Christian Hofmaier, Nicole Kronberger, Sheena Laursen, Anna Meijknecht, Salvör Nordal, Alexandre Quintanilha, Gema Revuelta, Núria Saladié, Judit Sándor, Júlio Borlido Santos, Simone Seyringer, Ilina Singh, Han Somsen, Winnie Toonders, Helge Torgersen, Vincent Torre, Márton Varju, Hub Zwart

    Public views on gene editing and its usesPublic views on gene editing and its uses, Published online: 09 November 2017; doi:10.1038/nbt.3958

    更新日期:2017-11-10
  • Recent patents related to germline modification
    Nat. Biotechnol. (IF 41.667) Pub Date : 2017-11-09

    Recent patents related to germline modificationRecent patents related to germline modification, Published online: 09 November 2017; doi:10.1038/nbt.4013

    更新日期:2017-11-10
  • Assisted reproductive technologies to prevent human mitochondrial disease transmission
    Nat. Biotechnol. (IF 41.667) Pub Date : 2017-11-09
    Andy Greenfield, Peter Braude, Frances Flinter, Robin Lovell-Badge, Caroline Ogilvie, Anthony C F Perry

    Assisted reproductive technologies to prevent human mitochondrial disease transmissionAssisted reproductive technologies to prevent human mitochondrial disease transmission, Published online: 09 November 2017; doi:10.1038/nbt.3997NatureArticleSnippet(type=short-summary, markup=Replacement of pathogenic mitochondrial DNA in human embryos is poised for clinical application., isJats=true)

    更新日期:2017-11-10
  • Revisiting the Warnock rule
    Nat. Biotechnol. (IF 41.667) Pub Date : 2017-11-09
    J Benjamin Hurlbut, Insoo Hyun, Aaron D Levine, Robin Lovell-Badge, Jeantine E Lunshof, Kirstin R W Matthews, Peter Mills, Alison Murdoch, Martin F Pera, Christopher Thomas Scott, Juliet Tizzard, Mary Warnock, Magdalena Zernicka-Goetz, Qi Zhou, Laurie Zoloth

    Revisiting the Warnock ruleRevisiting the Warnock rule, Published online: 09 November 2017; doi:10.1038/nbt.4015NatureArticleSnippet(type=standfirst, markup=Is it time to reassess the 14-day rule for human embryo research?, isJats=true)

    更新日期:2017-11-10
  • Duchenne drug clings on for FDA nod
    Nat. Biotechnol. (IF 41.667) Pub Date : 2017-11-09

    Duchenne drug clings on for FDA nodDuchenne drug clings on for FDA nod, Published online: 09 November 2017; doi:10.1038/nbt1117-999

    更新日期:2017-11-10
  • Ethical principles for the use of human cellular biotechnologies
    Nat. Biotechnol. (IF 41.667) Pub Date : 2017-11-09
    Paul Root Wolpe, Karen S Rommelfanger, the Drafting and Reviewing Delegates of the BEINGS Working Groups

    Ethical principles for the use of human cellular biotechnologiesEthical principles for the use of human cellular biotechnologies, Published online: 09 November 2017; doi:10.1038/nbt.4007NatureArticleSnippet(type=standfirst, markup=Recent developments in bioengineering promise the possibility of new diagnostic and treatment strategies, novel industrial processes, and innovative approaches to thorny problems in fields such as nutrition, agriculture, and biomanufacturing. As modern genetics has matured and developed technologies of increasing power, debates over risk assessments and proper applications of the technology, and over who should have decision-making power over such issues, have become more prominent. Recently, some scientists have advocated that ethicists “step out of the way,” whereas others have called for greater ethical scrutiny, or even for moratoria on some lines of research. As a community, however, we must together determine the proper application of these powerful biological tools. This paper, a consensus statement of a group of interdisciplinary delegates drawn from the top biotech-producing countries of the world, offers a set of ethical principles to contribute to the ethical conversation about human cellular biotechnological research moving forward., isJats=true)

    更新日期:2017-11-10
  • Spanish group defeats Shkreli in Chagas voucher race
    Nat. Biotechnol. (IF 41.667) Pub Date : 2017-11-09
    Lisa Melton

    Spanish group defeats Shkreli in Chagas voucher raceSpanish group defeats Shkreli in Chagas voucher race, Published online: 09 November 2017; doi:10.1038/nbt1117-1003

    更新日期:2017-11-10
  • First rounders: Stelios Papadopoulos
    Nat. Biotechnol. (IF 41.667) Pub Date : 2017-11-09

    First rounders: Stelios PapadopoulosFirst rounders: Stelios Papadopoulos, Published online: 09 November 2017; doi:10.1038/nbt.3995

    更新日期:2017-11-10
  • Public views on gene editing and its uses
    Nat. Biotechnol. (IF 41.667) Pub Date : 2017-11-09
    George Gaskell, Imre Bard, Agnes Allansdottir, Rui Vieira da Cunha, Peter Eduard, Juergen Hampel, Elisabeth Hildt, Christian Hofmaier, Nicole Kronberger, Sheena Laursen, Anna Meijknecht, Salvör Nordal, Alexandre Quintanilha, Gema Revuelta, Núria Saladié, Judit Sándor, Júlio Borlido Santos, Simone Seyringer, Ilina Singh, Han Somsen, Winnie Toonders, Helge Torgersen, Vincent Torre, Márton Varju, Hub Zwart

    Public views on gene editing and its usesPublic views on gene editing and its uses, Published online: 09 November 2017; doi:10.1038/nbt.3958

    更新日期:2017-11-10
  • Recent patents related to germline modification
    Nat. Biotechnol. (IF 41.667) Pub Date : 2017-11-09

    Recent patents related to germline modificationRecent patents related to germline modification, Published online: 09 November 2017; doi:10.1038/nbt.4013

    更新日期:2017-11-10
  • Assisted reproductive technologies to prevent human mitochondrial disease transmission
    Nat. Biotechnol. (IF 41.667) Pub Date : 2017-11-09
    Andy Greenfield, Peter Braude, Frances Flinter, Robin Lovell-Badge, Caroline Ogilvie, Anthony C F Perry

    Assisted reproductive technologies to prevent human mitochondrial disease transmissionAssisted reproductive technologies to prevent human mitochondrial disease transmission, Published online: 09 November 2017; doi:10.1038/nbt.3997NatureArticleSnippet(type=short-summary, markup=Replacement of pathogenic mitochondrial DNA in human embryos is poised for clinical application., isJats=true)

    更新日期:2017-11-10
  • Revisiting the Warnock rule
    Nat. Biotechnol. (IF 41.667) Pub Date : 2017-11-09
    J Benjamin Hurlbut, Insoo Hyun, Aaron D Levine, Robin Lovell-Badge, Jeantine E Lunshof, Kirstin R W Matthews, Peter Mills, Alison Murdoch, Martin F Pera, Christopher Thomas Scott, Juliet Tizzard, Mary Warnock, Magdalena Zernicka-Goetz, Qi Zhou, Laurie Zoloth

    Revisiting the Warnock ruleRevisiting the Warnock rule, Published online: 09 November 2017; doi:10.1038/nbt.4015NatureArticleSnippet(type=standfirst, markup=Is it time to reassess the 14-day rule for human embryo research?, isJats=true)

    更新日期:2017-11-10
  • GRID-seq reveals the global RNA–chromatin interactome
    Nat. Biotechnol. (IF 41.667) Pub Date : 
    Xiao Li, Bing Zhou, Liang Chen, Lan-Tao Gou, Hairi Li, Xiang-Dong Fu

    Higher eukaryotic genomes are bound by a large number of coding and non-coding RNAs, but approaches to comprehensively map the identity and binding sites of these RNAs are lacking. Here we report a method to capture in situ global RNA interactions with DNA by deep sequencing (GRID-seq), which enables the comprehensive identification of the entire repertoire of chromatin-interacting RNAs and their respective binding sites. In human, mouse, and Drosophila cells, we detected a large set of tissue-specific coding and non-coding RNAs that are bound to active promoters and enhancers, especially super-enhancers. Assuming that most mRNA–chromatin interactions indicate the physical proximity of a promoter and an enhancer, we constructed a three-dimensional global connectivity map of promoters and enhancers, revealing transcription-activity-linked genomic interactions in the nucleus.

    更新日期:2017-09-19
  • Pearl millet genome sequence provides a resource to improve agronomic traits in arid environments
    Nat. Biotechnol. (IF 41.667) Pub Date : 
    Rajeev K Varshney, Chengcheng Shi, Mahendar Thudi, Cedric Mariac, Jason Wallace, Peng Qi, He Zhang, Yusheng Zhao, Xiyin Wang, Abhishek Rathore, Rakesh K Srivastava, Annapurna Chitikineni, Guangyi Fan, Prasad Bajaj, Somashekhar Punnuri, S K Gupta, Hao Wang, Yong Jiang, Marie Couderc, Mohan A V S K Katta, Dev R Paudel, K D Mungra, Wenbin Chen, Karen R Harris-Shultz, Vanika Garg, Neetin Desai, Dadakhalandar Doddamani, Ndjido Ardo Kane, Joann A Conner, Arindam Ghatak, Palak Chaturvedi, Sabarinath Subramaniam, Om Parkash Yadav, Cécile Berthouly-Salazar, Falalou Hamidou, Jianping Wang, Xinming Liang, Jérémy Clotault, Hari D Upadhyaya, Philippe Cubry, Bénédicte Rhoné, Mame Codou Gueye, Ramanjulu Sunkar, Christian Dupuy, Francesca Sparvoli, Shifeng Cheng, R S Mahala, Bharat Singh, Rattan S Yadav, Eric Lyons, Swapan K Datta, C Tom Hash, Katrien M Devos, Edward Buckler, Jeffrey L Bennetzen, Andrew H Paterson, Peggy Ozias-Akins, Stefania Grando, Jun Wang, Trilochan Mohapatra, Wolfram We..

    Pearl millet [Cenchrus americanus (L.) Morrone] is a staple food for more than 90 million farmers in arid and semi-arid regions of sub-Saharan Africa, India and South Asia. We report the ~1.79 Gb draft whole genome sequence of reference genotype Tift 23D2B1-P1-P5, which contains an estimated 38,579 genes. We highlight the substantial enrichment for wax biosynthesis genes, which may contribute to heat and drought tolerance in this crop. We resequenced and analyzed 994 pearl millet lines, enabling insights into population structure, genetic diversity and domestication. We use these resequencing data to establish marker trait associations for genomic selection, to define heterotic pools, and to predict hybrid performance. We believe that these resources should empower researchers and breeders to improve this important staple crop.

    更新日期:2017-09-19
  • Shotgun metagenomics, from sampling to analysis
    Nat. Biotechnol. (IF 41.667) Pub Date : 
    Christopher Quince, Alan W Walker, Jared T Simpson, Nicholas J Loman, Nicola Segata

    Diverse microbial communities of bacteria, archaea, viruses and single-celled eukaryotes have crucial roles in the environment and in human health. However, microbes are frequently difficult to culture in the laboratory, which can confound cataloging of members and understanding of how communities function. High-throughput sequencing technologies and a suite of computational pipelines have been combined into shotgun metagenomics methods that have transformed microbiology. Still, computational approaches to overcome the challenges that affect both assembly-based and mapping-based metagenomic profiling, particularly of high-complexity samples or environments containing organisms with limited similarity to sequenced genomes, are needed. Understanding the functions and characterizing specific strains of these communities offers biotechnological promise in therapeutic discovery and innovative ways to synthesize products using microbial factories and can pinpoint the contributions of microorganisms to planetary, animal and human health.

    更新日期:2017-09-14
  • Blood feud erupts over Roche's bispecific antibody for hemophilia
    Nat. Biotechnol. (IF 41.667) Pub Date : 
    Elie Dolgin

    Blood feud erupts over Roche's bispecific antibody for hemophilia Nature Biotechnology, Published online: 11 September 2017; doi:10.1038/nbt0917-803

    更新日期:2017-09-14
  • Single-cell deep phenotyping of IgG-secreting cells for high-resolution immune monitoring
    Nat. Biotechnol. (IF 41.667) Pub Date : 2017-09-11
    Klaus Eyer, Raphaël C L Doineau, Carlos E Castrillon, Luis Briseño-Roa, Vera Menrath, Guillaume Mottet, Patrick England, Alexei Godina, Elodie Brient-Litzler, Clément Nizak, Allan Jensen, Andrew D Griffiths, Jérôme Bibette, Pierre Bruhns, Jean Baudry

    Single-cell deep phenotyping of IgG-secreting cells for high-resolution immune monitoring Nature Biotechnology, Published online: 11 September 2017; doi:10.1038/nbt.3964 An in-droplet immunoassay enables determination of the rate and affinity of secreted antigen-specific antibodies at the single-cell level.

    更新日期:2017-09-14
  • Challenges in the gene therapy commercial ecosystem
    Nat. Biotechnol. (IF 41.667) Pub Date : 
    Rahul Kapoor, Thomas Klueter, James M Wilson

    Challenges in the gene therapy commercial ecosystem Nature Biotechnology, Published online: 11 September 2017; doi:10.1038/nbt.3931

    更新日期:2017-09-14
  • Adenosine checkpoint agent blazes a trail, joins immunotherapy roster
    Nat. Biotechnol. (IF 41.667) Pub Date : 
    Ken Garber

    Adenosine checkpoint agent blazes a trail, joins immunotherapy roster Nature Biotechnology, Published online: 11 September 2017; doi:10.1038/nbt0917-805

    更新日期:2017-09-14
  • Analysis of somatic microsatellite indels identifies driver events in human tumors
    Nat. Biotechnol. (IF 41.667) Pub Date : 2017-09-11
    Yosef E Maruvka, Kent W Mouw, Rosa Karlic, Prasanna Parasuraman, Atanas Kamburov, Paz Polak, Nicholas J Haradhvala, Julian M Hess, Esther Rheinbay, Yehuda Brody, Amnon Koren, Lior Z Braunstein, Alan D'Andrea, Michael S Lawrence, Adam Bass, Andre Bernards, Franziska Michor, Gad Getz

    Microsatellites (MSs) are tracts of variable-length repeats of short DNA motifs that exhibit high rates of mutation in the form of insertions or deletions (indels) of the repeated motif. Despite their prevalence, the contribution of somatic MS indels to cancer has been largely unexplored, owing to difficulties in detecting them in short-read sequencing data. Here we present two tools: MSMuTect, for accurate detection of somatic MS indels, and MSMutSig, for identification of genes containing MS indels at a higher frequency than expected by chance. Applying MSMuTect to whole-exome data from 6,747 human tumors representing 20 tumor types, we identified >1,000 previously undescribed MS indels in cancer genes. Additionally, we demonstrate that the number and pattern of MS indels can accurately distinguish microsatellite-stable tumors from tumors with microsatellite instability, thus potentially improving classification of clinically relevant subgroups. Finally, we identified seven MS indel driver hotspots: four in known cancer genes (ACVR2A, RNF43, JAK1, and MSH3) and three in genes not previously implicated as cancer drivers (ESRP1, PRDM2, and DOCK3).

    更新日期:2017-09-14
  • Recent patents related to clinical applications of sequencing
    Nat. Biotechnol. (IF 41.667) Pub Date : 

    Recent patents related to clinical applications of sequencing Nature Biotechnology, Published online: 11 September 2017; doi:10.1038/nbt.3970

    更新日期:2017-09-14
  • Vertex CF data wow Wall Street
    Nat. Biotechnol. (IF 41.667) Pub Date : 

    Vertex CF data wow Wall Street Nature Biotechnology, Published online: 11 September 2017; doi:10.1038/nbt0917-807

    更新日期:2017-09-14
  • Buying time for transplants
    Nat. Biotechnol. (IF 41.667) Pub Date : 2017-09-11

    Funders need to pay more attention to research aimed at increasing the shelf life of human organs. Doing so could pay dividends for both transplantation and basic research.

    更新日期:2017-09-12
  • After Myriad, what makes a gene patent claim 'markedly different' from nature?
    Nat. Biotechnol. (IF 41.667) Pub Date : 2017-09-11
    Mateo Aboy, Johnathon Liddicoat, Kathleen Liddell, Matthew Jordan, Cristina Crespo

    Examining the types of claim amendments that have transformed isolated gene claims from patent-ineligible into eligible subject matter provides clarity into the threshold of eligibility for gene-related patents.

    更新日期:2017-09-12
  • Interpreting the T-cell receptor repertoire
    Nat. Biotechnol. (IF 41.667) Pub Date : 2017-09-11
    Robert A Holt

    T cell receptor sequence motifs can predict T cell antigen specificity.

    更新日期:2017-09-12
  • Tagging activated neurons with light
    Nat. Biotechnol. (IF 41.667) Pub Date : 2017-09-11
    Dheeraj S Roy, Teruhiro Okuyama, Susumu Tonegawa

    Two new protein tools translate neuronal activity into gene expression during a light-defined time window.

    更新日期:2017-09-12
  • Shotgun metagenomics, from sampling to analysis
    Nat. Biotechnol. (IF 41.667) Pub Date : 2017-09-12
    Christopher Quince, Alan W Walker, Jared T Simpson, Nicholas J Loman, Nicola Segata

    Diverse microbial communities of bacteria, archaea, viruses and single-celled eukaryotes have crucial roles in the environment and in human health. However, microbes are frequently difficult to culture in the laboratory, which can confound cataloging of members and understanding of how communities function. High-throughput sequencing technologies and a suite of computational pipelines have been combined into shotgun metagenomics methods that have transformed microbiology. Still, computational approaches to overcome the challenges that affect both assembly-based and mapping-based metagenomic profiling, particularly of high-complexity samples or environments containing organisms with limited similarity to sequenced genomes, are needed. Understanding the functions and characterizing specific strains of these communities offers biotechnological promise in therapeutic discovery and innovative ways to synthesize products using microbial factories and can pinpoint the contributions of microorganisms to planetary, animal and human health.

    更新日期:2017-09-12
  • Control of phosphorothioate stereochemistry substantially increases the efficacy of antisense oligonucleotides
    Nat. Biotechnol. (IF 41.667) Pub Date : 2017-08-21
    Naoki Iwamoto, David C D Butler, Nenad Svrzikapa, Susovan Mohapatra, Ivan Zlatev, Dinah W Y Sah, Meena, Stephany M Standley, Genliang Lu, Luciano H Apponi, Maria Frank-Kamenetsky, Jason Jingxin Zhang, Chandra Vargeese, Gregory L Verdine

    Whereas stereochemical purity in drugs has become the standard for small molecules, stereoisomeric mixtures containing as many as a half million components persist in antisense oligonucleotide (ASO) therapeutics because it has been feasible neither to separate the individual stereoisomers, nor to synthesize stereochemically pure ASOs. Here we report the development of a scalable synthetic process that yields therapeutic ASOs having high stereochemical and chemical purity. Using this method, we synthesized rationally designed stereopure components of mipomersen, a drug comprising 524,288 stereoisomers. We demonstrate that phosphorothioate (PS) stereochemistry substantially affects the pharmacologic properties of ASOs. We report that Sp-configured PS linkages are stabilized relative to Rp, providing stereochemical protection from pharmacologic inactivation of the drug. Further, we elucidated a triplet stereochemical code in the stereopure ASOs, 3′-SpSpRp, that promotes target RNA cleavage by RNase H1 in vitro and provides a more durable response in mice than stereorandom ASOs.

    更新日期:2017-09-12
  • Haplotype phasing of whole human genomes using bead-based barcode partitioning in a single tube
    Nat. Biotechnol. (IF 41.667) Pub Date : 2017-06-26
    Fan Zhang, Lena Christiansen, Jerushah Thomas, Dmitry Pokholok, Ros Jackson, Natalie Morrell, Yannan Zhao, Melissa Wiley, Emily Welch, Erich Jaeger, Ana Granat, Steven J Norberg, Aaron Halpern, Maria C Rogert, Mostafa Ronaghi, Jay Shendure, Niall Gormley, Kevin L Gunderson, Frank J Steemers

    Haplotype information for whole genomes is rapidly generated with a single-tube method.

    更新日期:2017-09-12
  • A calcium- and light-gated switch to induce gene expression in activated neurons
    Nat. Biotechnol. (IF 41.667) Pub Date : 2017-06-26
    Dongmin Lee, Jung Ho Hyun, Kanghoon Jung, Patrick Hannan, Hyung-Bae Kwon

    Gene expression is controlled in activated neurons in the mouse brain using a two-component optogenetic system.

    更新日期:2017-09-12
  • A light- and calcium-gated transcription factor for imaging and manipulating activated neurons
    Nat. Biotechnol. (IF 41.667) Pub Date : 2017-06-26
    Wenjing Wang, Craig P Wildes, Tanyaporn Pattarabanjird, Mateo I Sanchez, Gordon F Glober, Gillian A Matthews, Kay M Tye, Alice Y Ting

    Activity remodels neurons, altering their molecular, structural, and electrical characteristics. To enable the selective characterization and manipulation of these neurons, we present FLARE, an engineered transcription factor that drives expression of fluorescent proteins, opsins, and other genetically encoded tools only in the subset of neurons that experienced activity during a user-defined time window. FLARE senses the coincidence of elevated cytosolic calcium and externally applied blue light, which together produce translocation of a membrane-anchored transcription factor to the nucleus to drive expression of any transgene. In cultured rat neurons, FLARE gives a light-to-dark signal ratio of 120 and a high- to low-calcium signal ratio of 10 after 10 min of stimulation. Opsin expression permitted functional manipulation of FLARE-marked neurons. In adult mice, FLARE also gave light- and motor-activity-dependent transcription in the cortex. Due to its modular design, minute-scale temporal resolution, and minimal dark-state leak, FLARE should be useful for the study of activity-dependent processes in neurons and other cells that signal with calcium.

    更新日期:2017-09-12
  • An integrated expression atlas of miRNAs and their promoters in human and mouse
    Nat. Biotechnol. (IF 41.667) Pub Date : 2017-08-21
    Derek de Rie, Imad Abugessaisa, Tanvir Alam, Erik Arner, Peter Arner, Haitham Ashoor, Gaby Åström, Magda Babina, Nicolas Bertin, A Maxwell Burroughs, Ailsa J Carlisle, Carsten O Daub, Michael Detmar, Ruslan Deviatiiarov, Alexandre Fort, Claudia Gebhard, Daniel Goldowitz, Sven Guhl, Thomas J Ha, Jayson Harshbarger, Akira Hasegawa, Kosuke Hashimoto, Meenhard Herlyn, Peter Heutink, Kelly J Hitchens, Chung Chau Hon, Edward Huang, Yuri Ishizu, Chieko Kai, Takeya Kasukawa, Peter Klinken, Timo Lassmann, Charles-Henri Lecellier, Weonju Lee, Marina Lizio, Vsevolod Makeev, Anthony Mathelier, Yulia A Medvedeva, Niklas Mejhert, Christopher J Mungall, Shohei Noma, Mitsuhiro Ohshima, Mariko Okada-Hatakeyama, Helena Persson, Patrizia Rizzu, Filip Roudnicky, Pål Sætrom, Hiroki Sato, Jessica Severin, Jay W Shin, Rolf K Swoboda, Hiroshi Tarui, Hiroo Toyoda, Kristoffer Vitting-Seerup, Louise Winteringham, Yoko Yamaguchi, Kayoko Yasuzawa, Misako Yoneda, Noriko Yumoto, Susan Zabierowski, Peter G ..

    MicroRNAs (miRNAs) are short non-coding RNAs with key roles in cellular regulation. As part of the fifth edition of the Functional Annotation of Mammalian Genome (FANTOM5) project, we created an integrated expression atlas of miRNAs and their promoters by deep-sequencing 492 short RNA (sRNA) libraries, with matching Cap Analysis Gene Expression (CAGE) data, from 396 human and 47 mouse RNA samples. Promoters were identified for 1,357 human and 804 mouse miRNAs and showed strong sequence conservation between species. We also found that primary and mature miRNA expression levels were correlated, allowing us to use the primary miRNA measurements as a proxy for mature miRNA levels in a total of 1,829 human and 1,029 mouse CAGE libraries. We thus provide a broad atlas of miRNA expression and promoters in primary mammalian cells, establishing a foundation for detailed analysis of miRNA expression patterns and transcriptional control regions.

    更新日期:2017-09-12
  • An atlas of B-cell clonal distribution in the human body
    Nat. Biotechnol. (IF 41.667) Pub Date : 2017-08-21
    Wenzhao Meng, Bochao Zhang, Gregory W Schwartz, Aaron M Rosenfeld, Daqiu Ren, Joseph J C Thome, Dustin J Carpenter, Nobuhide Matsuoka, Harvey Lerner, Amy L Friedman, Tomer Granot, Donna L Farber, Mark J Shlomchik, Uri Hershberg, Eline T Luning Prak

    B-cell responses result in clonal expansion, and can occur in a variety of tissues. To define how B-cell clones are distributed in the body, we sequenced 933,427 B-cell clonal lineages and mapped them to eight different anatomic compartments in six human organ donors. We show that large B-cell clones partition into two broad networks—one spans the blood, bone marrow, spleen and lung, while the other is restricted to tissues within the gastrointestinal (GI) tract (jejunum, ileum and colon). Notably, GI tract clones display extensive sharing of sequence variants among different portions of the tract and have higher frequencies of somatic hypermutation, suggesting extensive and serial rounds of clonal expansion and selection. Our findings provide an anatomic atlas of B-cell clonal lineages, their properties and tissue connections. This resource serves as a foundation for studies of tissue-based immunity, including vaccine responses, infections, autoimmunity and cancer.

    更新日期:2017-09-12
  • What faculty hiring committees want
    Nat. Biotechnol. (IF 41.667) Pub Date : 2017-09-11
    Charles B Wright, Nathan L Vanderford

    PhD trainees aspiring to become faculty need to know the credentials search committees value most in an applicant.

    更新日期:2017-09-12
  • Replacing reprogramming factors with antibodies selected from combinatorial antibody libraries
    Nat. Biotechnol. (IF 41.667) Pub Date : 2017-09-11
    Joel W Blanchard, Jia Xie, Nadja El-Mecharrafie, Simon Gross, Sohyon Lee, Richard A Lerner, Kristin K Baldwin

    The reprogramming of differentiated cells into induced pluripotent stem cells (iPSCs) is usually achieved by exogenous induction of transcription by factors acting in the nucleus. In contrast, during development, signaling pathways initiated at the membrane induce differentiation. The central idea of this study is to identify antibodies that can catalyze cellular de-differentiation and nuclear reprogramming by acting at the cell surface. We screen a lentiviral library encoding ~100 million secreted and membrane-bound single-chain antibodies and identify antibodies that can replace either Sox2 and Myc (c-Myc) or Oct4 during reprogramming of mouse embryonic fibroblasts into iPSCs. We show that one Sox2-replacing antibody antagonizes the membrane-associated protein Basp1, thereby de-repressing nuclear factors WT1, Esrrb and Lin28a (Lin28) independent of Sox2. By manipulating this pathway, we identify three methods to generate iPSCs. Our results establish unbiased selection from autocrine combinatorial antibody libraries as a robust method to discover new biologics and uncover membrane-to-nucleus signaling pathways that regulate pluripotency and cell fate.

    更新日期:2017-09-11
  • Detection of dysregulated protein-association networks by high-throughput proteomics predicts cancer vulnerabilities
    Nat. Biotechnol. (IF 41.667) Pub Date : 2017-09-11
    John D Lapek, Patricia Greninger, Robert Morris, Arnaud Amzallag, Iulian Pruteanu-Malinici, Cyril H Benes, Wilhelm Haas

    Multiplexed mass spectrometry analysis of breast cancer cell lines uncovers co-regulation of protein abundance that predicts the vulnerabilities of different cancers to drugs.

    更新日期:2017-09-11
  • Mapping the secrets of the antibody pool
    Nat. Biotechnol. (IF 41.667) Pub Date : 2017-09-11
    Jonathan R McDaniel, Gregory C Ippolito, George Georgiou

    The progression of antibody-mediated immunity can now be monitored at high-throughput on a single-cell level.

    更新日期:2017-09-11
  • A calcium- and light-gated switch to induce gene expression in activated neurons
    Nat. Biotechnol. (IF 41.667) Pub Date : 2017-06-26
    Dongmin Lee, Jung Ho Hyun, Kanghoon Jung, Patrick Hannan, Hyung-Bae Kwon

    Gene expression is controlled in activated neurons in the mouse brain using a two-component optogenetic system.

    更新日期:2017-09-04
  • A light- and calcium-gated transcription factor for imaging and manipulating activated neurons
    Nat. Biotechnol. (IF 41.667) Pub Date : 2017-06-26
    Wenjing Wang, Craig P Wildes, Tanyaporn Pattarabanjird, Mateo I Sanchez, Gordon F Glober, Gillian A Matthews, Kay M Tye, Alice Y Ting

    Activity remodels neurons, altering their molecular, structural, and electrical characteristics. To enable the selective characterization and manipulation of these neurons, we present FLARE, an engineered transcription factor that drives expression of fluorescent proteins, opsins, and other genetically encoded tools only in the subset of neurons that experienced activity during a user-defined time window. FLARE senses the coincidence of elevated cytosolic calcium and externally applied blue light, which together produce translocation of a membrane-anchored transcription factor to the nucleus to drive expression of any transgene. In cultured rat neurons, FLARE gives a light-to-dark signal ratio of 120 and a high- to low-calcium signal ratio of 10 after 10 min of stimulation. Opsin expression permitted functional manipulation of FLARE-marked neurons. In adult mice, FLARE also gave light- and motor-activity-dependent transcription in the cortex. Due to its modular design, minute-scale temporal resolution, and minimal dark-state leak, FLARE should be useful for the study of activity-dependent processes in neurons and other cells that signal with calcium.

    更新日期:2017-09-04
  • Haplotype phasing of whole human genomes using bead-based barcode partitioning in a single tube
    Nat. Biotechnol. (IF 41.667) Pub Date : 2017-06-26
    Fan Zhang, Lena Christiansen, Jerushah Thomas, Dmitry Pokholok, Ros Jackson, Natalie Morrell, Yannan Zhao, Melissa Wiley, Emily Welch, Erich Jaeger, Ana Granat, Steven J Norberg, Aaron Halpern, Maria C Rogert, Mostafa Ronaghi, Jay Shendure, Niall Gormley, Kevin L Gunderson, Frank J Steemers

    Haplotype information for whole genomes is rapidly generated with a single-tube method.

    更新日期:2017-09-04
  • Multiplexed quantification of proteins and transcripts in single cells
    Nat. Biotechnol. (IF 41.667) Pub Date : 2017-08-30
    Vanessa M Peterson, Kelvin Xi Zhang, Namit Kumar, Jerelyn Wong, Lixia Li, Douglas C Wilson, Renee Moore, Terrill K McClanahan, Svetlana Sadekova, Joel A Klappenbach

    We present a tool to measure gene and protein expression levels in single cells with DNA-labeled antibodies and droplet microfluidics. Using the RNA expression and protein sequencing assay (REAP-seq), we quantified proteins with 82 barcoded antibodies and >20,000 genes in a single workflow. We used REAP-seq to assess the costimulatory effects of a CD27 agonist on human CD8+ lymphocytes and to identify and characterize an unknown cell type.

    更新日期:2017-09-04
  • An integrated expression atlas of miRNAs and their promoters in human and mouse
    Nat. Biotechnol. (IF 41.667) Pub Date : 2017-08-21
    Derek de Rie, Imad Abugessaisa, Tanvir Alam, Erik Arner, Peter Arner, Haitham Ashoor, Gaby Åström, Magda Babina, Nicolas Bertin, A Maxwell Burroughs, Ailsa J Carlisle, Carsten O Daub, Michael Detmar, Ruslan Deviatiiarov, Alexandre Fort, Claudia Gebhard, Daniel Goldowitz, Sven Guhl, Thomas J Ha, Jayson Harshbarger, Akira Hasegawa, Kosuke Hashimoto, Meenhard Herlyn, Peter Heutink, Kelly J Hitchens, Chung Chau Hon, Edward Huang, Yuri Ishizu, Chieko Kai, Takeya Kasukawa, Peter Klinken, Timo Lassmann, Charles-Henri Lecellier, Weonju Lee, Marina Lizio, Vsevolod Makeev, Anthony Mathelier, Yulia A Medvedeva, Niklas Mejhert, Christopher J Mungall, Shohei Noma, Mitsuhiro Ohshima, Mariko Okada-Hatakeyama, Helena Persson, Patrizia Rizzu, Filip Roudnicky, Pål Sætrom, Hiroki Sato, Jessica Severin, Jay W Shin, Rolf K Swoboda, Hiroshi Tarui, Hiroo Toyoda, Kristoffer Vitting-Seerup, Louise Winteringham, Yoko Yamaguchi, Kayoko Yasuzawa, Misako Yoneda, Noriko Yumoto, Susan Zabierowski, Peter G ..

    MicroRNAs (miRNAs) are short non-coding RNAs with key roles in cellular regulation. As part of the fifth edition of the Functional Annotation of Mammalian Genome (FANTOM5) project, we created an integrated expression atlas of miRNAs and their promoters by deep-sequencing 492 short RNA (sRNA) libraries, with matching Cap Analysis Gene Expression (CAGE) data, from 396 human and 47 mouse RNA samples. Promoters were identified for 1,357 human and 804 mouse miRNAs and showed strong sequence conservation between species. We also found that primary and mature miRNA expression levels were correlated, allowing us to use the primary miRNA measurements as a proxy for mature miRNA levels in a total of 1,829 human and 1,029 mouse CAGE libraries. We thus provide a broad atlas of miRNA expression and promoters in primary mammalian cells, establishing a foundation for detailed analysis of miRNA expression patterns and transcriptional control regions.

    更新日期:2017-09-04
  • An atlas of B-cell clonal distribution in the human body
    Nat. Biotechnol. (IF 41.667) Pub Date : 2017-08-21
    Wenzhao Meng, Bochao Zhang, Gregory W Schwartz, Aaron M Rosenfeld, Daqiu Ren, Joseph J C Thome, Dustin J Carpenter, Nobuhide Matsuoka, Harvey Lerner, Amy L Friedman, Tomer Granot, Donna L Farber, Mark J Shlomchik, Uri Hershberg, Eline T Luning Prak

    B-cell responses result in clonal expansion, and can occur in a variety of tissues. To define how B-cell clones are distributed in the body, we sequenced 933,427 B-cell clonal lineages and mapped them to eight different anatomic compartments in six human organ donors. We show that large B-cell clones partition into two broad networks—one spans the blood, bone marrow, spleen and lung, while the other is restricted to tissues within the gastrointestinal (GI) tract (jejunum, ileum and colon). Notably, GI tract clones display extensive sharing of sequence variants among different portions of the tract and have higher frequencies of somatic hypermutation, suggesting extensive and serial rounds of clonal expansion and selection. Our findings provide an anatomic atlas of B-cell clonal lineages, their properties and tissue connections. This resource serves as a foundation for studies of tissue-based immunity, including vaccine responses, infections, autoimmunity and cancer.

    更新日期:2017-09-04
  • Control of phosphorothioate stereochemistry substantially increases the efficacy of antisense oligonucleotides
    Nat. Biotechnol. (IF 41.667) Pub Date : 2017-08-21
    Naoki Iwamoto, David C D Butler, Nenad Svrzikapa, Susovan Mohapatra, Ivan Zlatev, Dinah W Y Sah, Stephany M Standley, Genliang Lu, Luciano H Apponi, Maria Frank-Kamenetsky, Jason Jingxin Zhang, Chandra Vargeese, Gregory L Verdine

    Whereas stereochemical purity in drugs has become the standard for small molecules, stereoisomeric mixtures containing as many as a half million components persist in antisense oligonucleotide (ASO) therapeutics because it has been feasible neither to separate the individual stereoisomers, nor to synthesize stereochemically pure ASOs. Here we report the development of a scalable synthetic process that yields therapeutic ASOs having high stereochemical and chemical purity. Using this method, we synthesized rationally designed stereopure components of mipomersen, a drug comprising 524,288 stereoisomers. We demonstrate that phosphorothioate (PS) stereochemistry substantially affects the pharmacologic properties of ASOs. We report that Sp-configured PS linkages are stabilized relative to Rp, providing stereochemical protection from pharmacologic inactivation of the drug. Further, we elucidated a triplet stereochemical code in the stereopure ASOs, 3′-SpSpRp, that promotes target RNA cleavage by RNase H1 in vitro and provides a more durable response in mice than stereorandom ASOs.

    更新日期:2017-09-04
  • People
    Nat. Biotechnol. (IF 41.667) Pub Date : 

    People Nature Biotechnology, Published online: 8 August 2017; doi:10.1038/nbt.3945

    更新日期:2017-09-04
  • Plant breeders test drive first open-source seed bank
    Nat. Biotechnol. (IF 41.667) Pub Date : 
    Lucas Laursen

    Plant breeders test drive first open-source seed bank Nature Biotechnology, Published online: 8 August 2017; doi:10.1038/nbt0817-700

    更新日期:2017-09-04
  • Retraction: DNA-guided genome editing using the Natronobacterium gregoryi Argonaute
    Nat. Biotechnol. (IF 41.667) Pub Date : 
    Feng Gao, Xiao Z Shen, Feng Jiang, Yongqiang Wu, Chunyu Han

    Retraction: DNA-guided genome editing using the Natronobacterium gregoryi Argonaute Nature Biotechnology, Published online: 8 August 2017; doi:10.1038/nbt0817-797a

    更新日期:2017-09-04
  • First multi-gene NGS diagnostic kit approved
    Nat. Biotechnol. (IF 41.667) Pub Date : 
    Mark Ratner

    First multi-gene NGS diagnostic kit approved Nature Biotechnology, Published online: 8 August 2017; doi:10.1038/nbt0817-699

    更新日期:2017-09-04
  • Time for the data to speak
    Nat. Biotechnol. (IF 41.667) Pub Date : 2017-08-02

    Retraction of a study claiming gene editing via an Argonaute enzyme illustrates the importance of post-publication peer review in the age of 24/7 media.

    更新日期:2017-08-09
  • Engineering the animal out of animal products
    Nat. Biotechnol. (IF 41.667) Pub Date : 2017-08-08
    Amber Dance

    Amber Dance reports on a new wave of domestication—turning cells, rather than animals, into food.

    更新日期:2017-08-09
Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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