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Nature Biotechnology

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https://www.readbyqxmd.com/read/28319085/synergistic-drug-combinations-for-cancer-identified-in-a-crispr-screen-for-pairwise-genetic-interactions
#1
Kyuho Han, Edwin E Jeng, Gaelen T Hess, David W Morgens, Amy Li, Michael C Bassik
Identification of effective combination therapies is critical to address the emergence of drug-resistant cancers, but direct screening of all possible drug combinations is infeasible. Here we introduce a CRISPR-based double knockout (CDKO) system that improves the efficiency of combinatorial genetic screening using an effective strategy for cloning and sequencing paired single guide RNA (sgRNA) libraries and a robust statistical scoring method for calculating genetic interactions (GIs) from CRISPR-deleted gene pairs...
March 20, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28288105/reduction-of-antinutritional-glucosinolates-in-brassica-oilseeds-by-mutation-of-genes-encoding-transporters
#2
Hussam Hassan Nour-Eldin, Svend Roesen Madsen, Steven Engelen, Morten Egevang Jørgensen, Carl Erik Olsen, Jonathan Sonne Andersen, David Seynnaeve, Thalia Verhoye, Rudy Fulawka, Peter Denolf, Barbara Ann Halkier
The nutritional value of Brassica seed meals is reduced by the presence of glucosinolates, which are toxic compounds involved in plant defense. Mutation of the genes encoding two glucosinolate transporters (GTRs) eliminated glucosinolates from Arabidopsis thaliana seeds, but translation of loss-of-function phenotypes into Brassica crops is challenging because Brassica is polyploid. We mutated one of seven and four of 12 GTR orthologs and reduced glucosinolate levels in seeds by 60-70% in two different Brassica species (Brassica rapa and Brassica juncea)...
March 13, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28288104/the-asthma-mobile-health-study-a-large-scale-clinical-observational-study-using-researchkit
#3
Yu-Feng Yvonne Chan, Pei Wang, Linda Rogers, Nicole Tignor, Micol Zweig, Steven G Hershman, Nicholas Genes, Erick R Scott, Eric Krock, Marcus Badgeley, Ron Edgar, Samantha Violante, Rosalind Wright, Charles A Powell, Joel T Dudley, Eric E Schadt
The feasibility of using mobile health applications to conduct observational clinical studies requires rigorous validation. Here, we report initial findings from the Asthma Mobile Health Study, a research study, including recruitment, consent, and enrollment, conducted entirely remotely by smartphone. We achieved secure bidirectional data flow between investigators and 7,593 participants from across the United States, including many with severe asthma. Our platform enabled prospective collection of longitudinal, multidimensional data (e...
March 13, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28288103/reproducibility-of-computational-workflows-is-automated-using-continuous-analysis
#4
Brett K Beaulieu-Jones, Casey S Greene
Replication, validation and extension of experiments are crucial for scientific progress. Computational experiments are scriptable and should be easy to reproduce. However, computational analyses are designed and run in a specific computing environment, which may be difficult or impossible to match using written instructions. We report the development of continuous analysis, a workflow that enables reproducible computational analyses. Continuous analysis combines Docker, a container technology akin to virtual machines, with continuous integration, a software development technique, to automatically rerun a computational analysis whenever updates or improvements are made to source code or data...
March 13, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28288102/a-fret-sensor-enables-quantitative-measurements-of-membrane-charges-in-live-cells
#5
Yuanqing Ma, Yui Yamamoto, Philip R Nicovich, Jesse Goyette, Jérémie Rossy, J Justin Gooding, Katharina Gaus
Membrane charge has a critical role in protein trafficking and signaling. However, quantification of the effective electrostatic potential of cellular membranes has remained challenging. We developed a fluorescence membrane charge sensor (MCS) that reports changes in the membrane charge of live cells via Förster resonance energy transfer (FRET). MCS is permanently attached to the inner leaflet of the plasma membrane and shows a linear, reversible and fast response to changes of the electrostatic potential...
March 13, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28263296/guidescan-software-for-improved-single-and-paired-crispr-guide-rna-design
#6
Alexendar R Perez, Yuri Pritykin, Joana A Vidigal, Sagar Chhangawala, Lee Zamparo, Christina S Leslie, Andrea Ventura
We present GuideScan software for the design of CRISPR guide RNA libraries that can be used to edit coding and noncoding genomic regions. GuideScan produces high-density sets of guide RNAs (gRNAs) for single- and paired-gRNA genome-wide screens. We also show that the trie data structure of GuideScan enables the design of gRNAs that are more specific than those designed by existing tools.
March 6, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28263295/prediction-of-potent-shrnas-with-a-sequential-classification-algorithm
#7
Raphael Pelossof, Lauren Fairchild, Chun-Hao Huang, Christian Widmer, Vipin T Sreedharan, Nishi Sinha, Dan-Yu Lai, Yuanzhe Guan, Prem K Premsrirut, Darjus F Tschaharganeh, Thomas Hoffmann, Vishal Thapar, Qing Xiang, Ralph J Garippa, Gunnar Rätsch, Johannes Zuber, Scott W Lowe, Christina S Leslie, Christof Fellmann
We present SplashRNA, a sequential classifier to predict potent microRNA-based short hairpin RNAs (shRNAs). Trained on published and novel data sets, SplashRNA outperforms previous algorithms and reliably predicts the most efficient shRNAs for a given gene. Combined with an optimized miR-E backbone, >90% of high-scoring SplashRNA predictions trigger >85% protein knockdown when expressed from a single genomic integration. SplashRNA can significantly improve the accuracy of loss-of-function genetics studies and facilitates the generation of compact shRNA libraries...
March 6, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28244995/highly-efficient-rna-guided-base-editing-in-mouse-embryos
#8
Kyoungmi Kim, Seuk-Min Ryu, Sang-Tae Kim, Gayoung Baek, Daesik Kim, Kayeong Lim, Eugene Chung, Sunghyun Kim, Jin-Soo Kim
Base editors (BEs) composed of a cytidine deaminase fused to CRISPR-Cas9 convert cytidine to uridine, leading to single-base-pair substitutions in eukaryotic cells. We delivered BE mRNA or ribonucleoproteins targeting the Dmd or Tyr gene via electroporation or microinjection into mouse zygotes. F0 mice showed nonsense mutations with an efficiency of 44-57% and allelic frequencies of up to 100%, demonstrating an efficient method to generate mice with targeted point mutations.
February 27, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28244994/precise-base-editing-in-rice-wheat-and-maize-with-a-cas9-cytidine-deaminase-fusion
#9
Yuan Zong, Yanpeng Wang, Chao Li, Rui Zhang, Kunling Chen, Yidong Ran, Jin-Long Qiu, Daowen Wang, Caixia Gao
Targeted base editing in plants without the need for a foreign DNA donor or double-stranded DNA cleavage would accelerate genome modification and breeding in a wide array of crops. We used a CRISPR-Cas9 nickase-cytidine deaminase fusion to achieve targeted conversion of cytosine to thymine from position 3 to 9 within the protospacer in both protoplasts and regenerated rice, wheat and maize plants at frequencies of up to 43.48%.
February 27, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28191903/efficient-genome-editing-in-the-mouse-brain-by-local-delivery-of-engineered-cas9-ribonucleoprotein-complexes
#10
Brett T Staahl, Madhurima Benekareddy, Claire Coulon-Bainier, Ashwin A Banfal, Stephen N Floor, Jennifer K Sabo, Cole Urnes, Gabriela Acevedo Munares, Anirvan Ghosh, Jennifer A Doudna
We demonstrate editing of post-mitotic neurons in the adult mouse brain following injection of Cas9 ribonucleoprotein (RNP) complexes in the hippocampus, striatum and cortex. Engineered variants of Cas9 with multiple SV40 nuclear localization sequences enabled a tenfold increase in the efficiency of neuronal editing in vivo. These advances indicate the potential of genome editing in the brain to correct or inactivate the underlying genetic causes of neurological diseases.
February 13, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28191901/increasing-the-genome-targeting-scope-and-precision-of-base-editing-with-engineered-cas9-cytidine-deaminase-fusions
#11
Y Bill Kim, Alexis C Komor, Jonathan M Levy, Michael S Packer, Kevin T Zhao, David R Liu
Base editing induces single-nucleotide changes in the DNA of living cells using a fusion protein containing a catalytically defective Streptococcus pyogenes Cas9, a cytidine deaminase, and an inhibitor of base excision repair. This genome editing approach has the advantage that it does not require formation of double-stranded DNA breaks or provision of a donor DNA template. Here we report the development of five C to T (or G to A) base editors that use natural and engineered Cas9 variants with different protospacer-adjacent motif (PAM) specificities to expand the number of sites that can be targeted by base editing 2...
February 13, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28267741/hearing-in-the-mouse-of-usher
#12
John V Brigande
No abstract text is available yet for this article.
March 7, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28267740/new-york-spreads-the-news-with-1-15-billion-biotech-plan
#13
Gautam Naik
No abstract text is available yet for this article.
March 7, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28267739/in-this-issue
#14
(no author information available yet)
No abstract text is available yet for this article.
March 7, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28267738/around-the-world-in-a-month
#15
(no author information available yet)
No abstract text is available yet for this article.
March 7, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28267737/recent-patents-in-chimeric-antigen-receptors
#16
(no author information available yet)
No abstract text is available yet for this article.
March 7, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28267736/gender-tokenism-and-bias-prevail-in-biotech-boardrooms
#17
Elie Dolgin
No abstract text is available yet for this article.
March 7, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28267735/first-rounders-podcast-stephen-quake
#18
(no author information available yet)
No abstract text is available yet for this article.
March 7, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28267734/international-mentoring-as-a-new-educational-approach-to-alleviate-brain-drain-empower-young-talent-and-internationalize-higher-education
#19
María Soriano-Carot, Rosa Bretón-Romero, Joaquín López-Herraiz, Rocío López-Diego, Abel Suárez-Fueyo, Gemma Pellissa Prades, Rosario Fernandez-Godino, Daniel Navarro-Gomez, Amaranta Saguar, David Nieto, Laura Sánchez-García, Borja Peropadre, Zafira Castano
No abstract text is available yet for this article.
March 7, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28267733/us-immigration-order-strikes-against-biotech
#20
Jeremy M Levin, Steven H Holtzman, John Maraganore, Paul J Hastings, Ron Cohen, Bassil Dahiyat, Julian Adams, Chris Adams, Brett Ahrens, Jeff Albers, Mara G Aspinall, James E Audia, Martin Babler, Peter Barrett, Zoe Barry, Nessan Bermingham, Stephen Bloch, Robert I Blum, Paul B Bolno, Michael W Bonney, Bruce Booth, Daniel M Bradbury, Steven K Brauer, Brook Byers, Pablo J Cagnoni, Brian M Cali, Isaac Ciechanover, Chip Clark, Michael D Clayman, Jeff L Cleland, Paula Cobb, Ron Cooper, Mark G Currie, John Diekman, Eric L Dobmeier, Doug Doerfler, Elizabeth Lr Donley, Deborah Dunsire, Matthew During, Jens W Eckstein, Eric Elenko, Neil A Exter, Jonathan J Fleming, Gregory J Flesher, Jean-Francois Formela, Robert Forrester, Cedric Francois, Heather Franklin, Mason W Freeman, Howard Furst, Leonard Patrick Gage, Nicholas Galakatos, Brian M Gallagher, James A Geraghty, Simba Gill, David V Goeddel, Mark A Goldsmith, Maxine Gowen, Vikas Goyal, Tom Graney, David Grayzel, Barry Greene, Paul Grint, J C Gutierrez-Ramos, Bill Haney, Tuan Ha-Ngoc, Tim Harris, Faheem Hasnain, Yujiro Steve Hata, Peter Hecht, Leslie Henshaw, Rich Heyman, Herve Hoppenot, H Robert Horvitz, Thomas E Hughes, Wende S Hutton, Stephen T Isaacs, Annalisa Jenkins, Jeff Jonker, Jeff Kaplan, Perry Karsen, Jeb Keiper, Jean Kim, Jeff Kindler, Rachel King, Vanessa King, Nina Kjellson, Scott Koenig, Gerhard Koenig, Peter Kolchinsky, Paul Laikind, Robert Bob Langer, John J Lee, Jonathan S Leff, Bruce A Leicher, Nick Leschly, Andrew Levin, Mark Levin, Arnold J Levine, Alan Levy, David R Liu, Harvey F Lodish, Uri Lopatin, Ted W Love, Guy Macdonald, Gail J Maderis, Ankit Mahadevia, Nagesh K Mahanthappa, Joel F Martin, Alex Martin, W Eddie Martucci, James G McArthur, Corey M McCann, Sean A McCarthy, C Geoffrey McDonough, John Mendlein, Larry Miller, Diego Miralles, Kenneth I Moch, Bob More, Andrew G Myers, Michael A Narachi, Amir Nashat, Wendy Nelson, William J Newell, Bernat Olle, John E Osborn, Julia C Owens, Atul Pande, Stelios Papadopoulos, H Stewart Parker, Kush M Parmar, Matthew R Patterson, Steve M Paul, Rob Perez, Matthew Perry, Cary G Pfeffer, Mike Powell, Mark Pruzanski, Dennis J Purcell, Amit Rakhit, Kartik Ramamoorthi, William Rastetter, Adrian Ad Rawcliffe, Laurence E Reid, Ron C Renaud, Jason P Rhodes, William J Rieflin, Chad Robins, Scott M Rocklage, Michael Rosenblatt, Jonathan G Rosin, William J Rutter, Saurabh Saha, Camille Samuels, Vicki L Sato, George Scangos, John A Scarlett, David Schenkein, Stuart L Schreiber, Andrew Schwab, Paul Sekhri, Rajeev Shah, Thomas Shenk, Clay B Siegall, Nick J Simon, Nancy Simonian, Jeff Stein, Michael Su, Mary T Szela, Marco Taglietti, Nina Tandon, Henri Termeer, Nancy A Thornberry, Martin Tolar, Richard Ulevitch, Akshay K Vaishnaw, Anne VanLent, Martin Varsavsky, George P Vlasuk, Michel Vounatsos, Samuel G Waksal, Neil Warma, Ryan J Watts, Yaron Werber, Christoph Westphal, Wendell Wierenga, Doug E Williams, Lewis Rusty Williams, Kleanthis G Xanthopoulos, Daphne Zohar, Sandford Sandy Zweifach
No abstract text is available yet for this article.
March 7, 2017: Nature Biotechnology
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