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Nature Biotechnology

Arthur M Krieg
No abstract text is available yet for this article.
May 10, 2019: Nature Biotechnology
Charles Schmidt
No abstract text is available yet for this article.
May 8, 2019: Nature Biotechnology
Ho Bin Jang, Benjamin Bolduc, Olivier Zablocki, Jens H Kuhn, Simon Roux, Evelien M Adriaenssens, J Rodney Brister, Andrew M Kropinski, Mart Krupovic, Rob Lavigne, Dann Turner, Matthew B Sullivan
Microbiomes from every environment contain a myriad of uncultivated archaeal and bacterial viruses, but studying these viruses is hampered by the lack of a universal, scalable taxonomic framework. We present vConTACT v.2.0, a network-based application utilizing whole genome gene-sharing profiles for virus taxonomy that integrates distance-based hierarchical clustering and confidence scores for all taxonomic predictions. We report near-identical (96%) replication of existing genus-level viral taxonomy assignments from the International Committee on Taxonomy of Viruses for National Center for Biotechnology Information virus RefSeq...
May 6, 2019: Nature Biotechnology
Brian Hie, Bryan Bryson, Bonnie Berger
Integration of single-cell RNA sequencing (scRNA-seq) data from multiple experiments, laboratories and technologies can uncover biological insights, but current methods for scRNA-seq data integration are limited by a requirement for datasets to derive from functionally similar cells. We present Scanorama, an algorithm that identifies and merges the shared cell types among all pairs of datasets and accurately integrates heterogeneous collections of scRNA-seq data. We applied Scanorama to integrate and remove batch effects across 105,476 cells from 26 diverse scRNA-seq experiments representing 9 different technologies...
May 6, 2019: Nature Biotechnology
Aaron M Newman, Chloé B Steen, Chih Long Liu, Andrew J Gentles, Aadel A Chaudhuri, Florian Scherer, Michael S Khodadoust, Mohammad S Esfahani, Bogdan A Luca, David Steiner, Maximilian Diehn, Ash A Alizadeh
Single-cell RNA-sequencing has emerged as a powerful technique for characterizing cellular heterogeneity, but it is currently impractical on large sample cohorts and cannot be applied to fixed specimens collected as part of routine clinical care. We previously developed an approach for digital cytometry, called CIBERSORT, that enables estimation of cell type abundances from bulk tissue transcriptomes. We now introduce CIBERSORTx, a machine learning method that extends this framework to infer cell-type-specific gene expression profiles without physical cell isolation...
May 6, 2019: Nature Biotechnology
Jingying Zhang, Yong-Xin Liu, Na Zhang, Bin Hu, Tao Jin, Haoran Xu, Yuan Qin, Pengxu Yan, Xiaoning Zhang, Xiaoxuan Guo, Jing Hui, Shouyun Cao, Xin Wang, Chao Wang, Hui Wang, Baoyuan Qu, Guangyi Fan, Lixing Yuan, Ruben Garrido-Oter, Chengcai Chu, Yang Bai
Nitrogen-use efficiency of indica varieties of rice is superior to that of japonica varieties. We apply 16S ribosomal RNA gene profiling to characterize root microbiota of 68 indica and 27 japonica varieties grown in the field. We find that indica and japonica recruit distinct root microbiota. Notably, indica-enriched bacterial taxa are more diverse, and contain more genera with nitrogen metabolism functions, than japonica-enriched taxa. Using genetic approaches, we provide evidence that NRT1.1B, a rice nitrate transporter and sensor, is associated with the recruitment of a large proportion of indica-enriched bacteria...
April 29, 2019: Nature Biotechnology
Wen Shen, Cheryl L De Hoyos, Michael T Migawa, Timothy A Vickers, Hong Sun, Audrey Low, Thomas A Bell, Meghdad Rahdar, Swagatam Mukhopadhyay, Christopher E Hart, Melanie Bell, Stan Riney, Susan F Murray, Sarah Greenlee, Rosanne M Crooke, Xue-Hai Liang, Punit P Seth, Stanley T Crooke
The molecular mechanisms of toxicity of chemically modified phosphorothioate antisense oligonucleotides (PS-ASOs) are not fully understood. Here, we report that toxic gapmer PS-ASOs containing modifications such as constrained ethyl (cEt), locked nucleic acid (LNA) and 2'-O-methoxyethyl (2'-MOE) bind many cellular proteins with high avidity, altering their function, localization and stability. We show that RNase H1-dependent delocalization of paraspeckle proteins to nucleoli is an early event in PS-ASO toxicity, followed by nucleolar stress, p53 activation and apoptotic cell death...
April 29, 2019: Nature Biotechnology
Matthew T Noakes, Henry Brinkerhoff, Andrew H Laszlo, Ian M Derrington, Kyle W Langford, Jonathan W Mount, Jasmine L Bowman, Katherine S Baker, Kenji M Doering, Benjamin I Tickman, Jens H Gundlach
Nanopore DNA sequencing is limited by low base-calling accuracy. Improved base-calling accuracy has so far relied on specialized base-calling algorithms, different nanopores and motor enzymes, or biochemical methods to re-read DNA molecules. Two primary error modes hamper sequencing accuracy: enzyme mis-steps and sequences with indistinguishable signals. We vary the driving voltage from 100 to 200 mV, with a frequency of 200 Hz, across a Mycobacterium smegmatis porin A (MspA) nanopore, thus changing how the DNA strand moves through the nanopore...
April 22, 2019: Nature Biotechnology
Jia Chen, Bei Yang, Li Yang
No abstract text is available yet for this article.
April 18, 2019: Nature Biotechnology
Rocío López-Igual, Joaquín Bernal-Bayard, Alfonso Rodríguez-Patón, Jean-Marc Ghigo, Didier Mazel
Targeted killing of pathogenic bacteria without harming beneficial members of host microbiota holds promise as a strategy to cure disease and limit both antimicrobial-related dysbiosis and development of antimicrobial resistance. We engineer toxins that are split by inteins and deliver them by conjugation into a mixed population of bacteria. Our toxin-intein antimicrobial is only activated in bacteria that harbor specific transcription factors. We apply our antimicrobial to specifically target and kill antibiotic-resistant Vibrio cholerae present in mixed populations...
April 15, 2019: Nature Biotechnology
D Dewran Kocak, Eric A Josephs, Vidit Bhandarkar, Shaunak S Adkar, Jennifer B Kwon, Charles A Gersbach
CRISPR (clustered regularly interspaced short palindromic repeat) systems have been broadly adopted for basic science, biotechnology, and gene and cell therapy. In some cases, these bacterial nucleases have demonstrated off-target activity. This creates a potential hazard for therapeutic applications and could confound results in biological research. Therefore, improving the precision of these nucleases is of broad interest. Here we show that engineering a hairpin secondary structure onto the spacer region of single guide RNAs (hp-sgRNAs) can increase specificity by several orders of magnitude when combined with various CRISPR effectors...
April 15, 2019: Nature Biotechnology
Jacob L Litke, Samie R Jaffrey
RNA aptamers and RNA aptamer-based devices can be genetically encoded and expressed in cells to probe and manipulate cellular function. However, their usefulness in the mammalian cell is limited by low expression and rapid degradation. Here we describe the Tornado (Twister-optimized RNA for durable overexpression) expression system for achieving rapid RNA circularization, resulting in RNA aptamers with high stability and expression levels. Tornado-expressed transcripts contain an RNA of interest flanked by Twister ribozymes...
April 8, 2019: Nature Biotechnology
Michael Eisenstein
No abstract text is available yet for this article.
April 5, 2019: Nature Biotechnology
Cormac Sheridan
No abstract text is available yet for this article.
April 5, 2019: Nature Biotechnology
Justin M Zook, Jennifer McDaniel, Nathan D Olson, Justin Wagner, Hemang Parikh, Haynes Heaton, Sean A Irvine, Len Trigg, Rebecca Truty, Cory Y McLean, Francisco M De La Vega, Chunlin Xiao, Stephen Sherry, Marc Salit
Benchmark small variant calls are required for developing, optimizing and assessing the performance of sequencing and bioinformatics methods. Here, as part of the Genome in a Bottle (GIAB) Consortium, we apply a reproducible, cloud-based pipeline to integrate multiple short- and linked-read sequencing datasets and provide benchmark calls for human genomes. We generate benchmark calls for one previously analyzed GIAB sample, as well as six genomes from the Personal Genome Project. These new genomes have broad, open consent, making this a 'first of its kind' resource that is available to the community for multiple downstream applications...
April 1, 2019: Nature Biotechnology
Vikram Virdi, Jorge Palaci, Bram Laukens, Stefan Ryckaert, Eric Cox, Erik Vanderbeke, Ann Depicker, Nico Callewaert
Oral antibodies that interfere with gastrointestinal targets and can be manufactured at scale are needed. Here we show that a single-gene-encoded monomeric immunoglobulin A (IgA)-like antibody, composed of camelid variable single domain antibodies (VHH) fused to IgA Fc (mVHH-IgA), prevents infection by enterotoxigenic Escherichia coli (F4-ETEC) in piglets. The mVHH-IgA can be produced in soybean seeds or secreted from the yeast Pichia pastoris, freeze- or spray-dried and orally delivered within food.
April 1, 2019: Nature Biotechnology
Wouter Saelens, Robrecht Cannoodt, Helena Todorov, Yvan Saeys
Trajectory inference approaches analyze genome-wide omics data from thousands of single cells and computationally infer the order of these cells along developmental trajectories. Although more than 70 trajectory inference tools have already been developed, it is challenging to compare their performance because the input they require and output models they produce vary substantially. Here, we benchmark 45 of these methods on 110 real and 229 synthetic datasets for cellular ordering, topology, scalability and usability...
April 1, 2019: Nature Biotechnology
Peter Krusche, Len Trigg, Paul C Boutros, Christopher E Mason, Francisco M De La Vega, Benjamin L Moore, Mar Gonzalez-Porta, Michael A Eberle, Zivana Tezak, Samir Lababidi, Rebecca Truty, George Asimenos, Birgit Funke, Mark Fleharty, Brad A Chapman, Marc Salit, Justin M Zook
In the version of this article initially published online, two pairs of headings were switched with each other in Table 4: "Recall (PCR free)" was switched with "Recall (with PCR)," and "Precision (PCR free)" was switched with "Precision (with PCR)." The error has been corrected in the print, PDF and HTML versions of this article.
March 21, 2019: Nature Biotechnology
Manu Setty, Vaidotas Kiseliovas, Jacob Levine, Adam Gayoso, Linas Mazutis, Dana Pe'er
Single-cell RNA sequencing studies of differentiating systems have raised fundamental questions regarding the discrete versus continuous nature of both differentiation and cell fate. Here we present Palantir, an algorithm that models trajectories of differentiating cells by treating cell fate as a probabilistic process and leverages entropy to measure cell plasticity along the trajectory. Palantir generates a high-resolution pseudo-time ordering of cells and, for each cell state, assigns a probability of differentiating into each terminal state...
March 21, 2019: Nature Biotechnology
Marc Fiume, Miroslav Cupak, Stephen Keenan, Jordi Rambla, Sabela de la Torre, Stephanie O M Dyke, Anthony J Brookes, Knox Carey, David Lloyd, Peter Goodhand, Maximilian Haeussler, Michael Baudis, Heinz Stockinger, Lena Dolman, Ilkka Lappalainen, Juha Törnroos, Mikael Linden, J Dylan Spalding, Saif Ur-Rehman, Angela Page, Paul Flicek, Stephen Sherry, David Haussler, Susheel Varma, Gary Saunders, Serena Scollen
In the version of this article initially published, Lena Dolman's second affiliation was given as Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK. The correct second affiliation is Ontario Institute for Cancer Research, Toronto, Ontario, Canada. The error has been corrected in the HTML and PDF versions of the article.
March 20, 2019: Nature Biotechnology
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