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Nature Biotechnology

Elie Dolgin
In the version of this article initially published, Betalutin was described as directing a radioisotope to CD45-expressing B cells; in fact, it directs it to CD37-expressing B cells. The error has been corrected in the HTML and PDF versions of the article.
January 18, 2019: Nature Biotechnology
Chun Wang, Qing Liu, Yi Shen, Yufeng Hua, Junjie Wang, Jianrong Lin, Mingguo Wu, Tingting Sun, Zhukuan Cheng, Raphael Mercier, Kejian Wang
Heterosis, or hybrid vigor, is exploited by breeders to produce elite high-yielding crop lines, but beneficial phenotypes are lost in subsequent generations owing to genetic segregation. Clonal propagation through seeds would enable self-propagation of F1 hybrids. Here we report a strategy to enable clonal reproduction of F1 rice hybrids through seeds. We fixed the heterozygosity of F1 hybrid rice by multiplex CRISPR-Cas9 genome editing of the REC8, PAIR1 and OSD1 meiotic genes to produce clonal diploid gametes and tetraploid seeds...
January 4, 2019: Nature Biotechnology
Rayner M L Queiroz, Tom Smith, Eneko Villanueva, Maria Marti-Solano, Mie Monti, Mariavittoria Pizzinga, Dan-Mircea Mirea, Manasa Ramakrishna, Robert F Harvey, Veronica Dezi, Gavin H Thomas, Anne E Willis, Kathryn S Lilley
Existing high-throughput methods to identify RNA-binding proteins (RBPs) are based on capture of polyadenylated RNAs and cannot recover proteins that interact with nonadenylated RNAs, including long noncoding RNA, pre-mRNAs and bacterial RNAs. We present orthogonal organic phase separation (OOPS), which does not require molecular tagging or capture of polyadenylated RNA, and apply it to recover cross-linked protein-RNA and free protein, or protein-bound RNA and free RNA, in an unbiased way. We validated OOPS in HEK293, U2OS and MCF10A human cell lines, and show that 96% of proteins recovered were bound to RNA...
January 3, 2019: Nature Biotechnology
Young-Gyun Park, Chang Ho Sohn, Ritchie Chen, Margaret McCue, Dae Hee Yun, Gabrielle T Drummond, Taeyun Ku, Nicholas B Evans, Hayeon Caitlyn Oak, Wendy Trieu, Heejin Choi, Xin Jin, Varoth Lilascharoen, Ji Wang, Matthias C Truttmann, Helena W Qi, Hidde L Ploegh, Todd R Golub, Shih-Chi Chen, Matthew P Frosch, Heather J Kulik, Byung Kook Lim, Kwanghun Chung
Understanding complex biological systems requires the system-wide characterization of both molecular and cellular features. Existing methods for spatial mapping of biomolecules in intact tissues suffer from information loss caused by degradation and tissue damage. We report a tissue transformation strategy named stabilization under harsh conditions via intramolecular epoxide linkages to prevent degradation (SHIELD), which uses a flexible polyepoxide to form controlled intra- and intermolecular cross-link with biomolecules...
December 17, 2018: Nature Biotechnology
Simon Roux, Evelien M Adriaenssens, Bas E Dutilh, Eugene V Koonin, Andrew M Kropinski, Mart Krupovic, Jens H Kuhn, Rob Lavigne, J Rodney Brister, Arvind Varsani, Clara Amid, Ramy K Aziz, Seth R Bordenstein, Peer Bork, Mya Breitbart, Guy R Cochrane, Rebecca A Daly, Christelle Desnues, Melissa B Duhaime, Joanne B Emerson, François Enault, Jed A Fuhrman, Pascal Hingamp, Philip Hugenholtz, Bonnie L Hurwitz, Natalia N Ivanova, Jessica M Labonté, Kyung-Bum Lee, Rex R Malmstrom, Manuel Martinez-Garcia, Ilene Karsch Mizrachi, Hiroyuki Ogata, David Páez-Espino, Marie-Agnès Petit, Catherine Putonti, Thomas Rattei, Alejandro Reyes, Francisco Rodriguez-Valera, Karyna Rosario, Lynn Schriml, Frederik Schulz, Grieg F Steward, Matthew B Sullivan, Shinichi Sunagawa, Curtis A Suttle, Ben Temperton, Susannah G Tringe, Rebecca Vega Thurber, Nicole S Webster, Katrine L Whiteson, Steven W Wilhelm, K Eric Wommack, Tanja Woyke, Kelly C Wrighton, Pelin Yilmaz, Takashi Yoshida, Mark J Young, Natalya Yutin, Lisa Zeigler Allen, Nikos C Kyrpides, Emiley A Eloe-Fadrosh
We present an extension of the Minimum Information about any (x) Sequence (MIxS) standard for reporting sequences of uncultivated virus genomes. Minimum Information about an Uncultivated Virus Genome (MIUViG) standards were developed within the Genomic Standards Consortium framework and include virus origin, genome quality, genome annotation, taxonomic classification, biogeographic distribution and in silico host prediction. Community-wide adoption of MIUViG standards, which complement the Minimum Information about a Single Amplified Genome (MISAG) and Metagenome-Assembled Genome (MIMAG) standards for uncultivated bacteria and archaea, will improve the reporting of uncultivated virus genomes in public databases...
December 17, 2018: Nature Biotechnology
Brendan Bulik-Sullivan, Jennifer Busby, Christine D Palmer, Matthew J Davis, Tyler Murphy, Andrew Clark, Michele Busby, Fujiko Duke, Aaron Yang, Lauren Young, Noelle C Ojo, Kamilah Caldwell, Jesse Abhyankar, Thomas Boucher, Meghan G Hart, Vladimir Makarov, Vincent Thomas De Montpreville, Olaf Mercier, Timothy A Chan, Giorgio Scagliotti, Paolo Bironzo, Silvia Novello, Niki Karachaliou, Rafael Rosell, Ian Anderson, Nashat Gabrail, John Hrom, Chainarong Limvarapuss, Karin Choquette, Alexander Spira, Raphael Rousseau, Cynthia Voong, Naiyer A Rizvi, Elie Fadel, Mark Frattini, Karin Jooss, Mojca Skoberne, Joshua Francis, Roman Yelensky
Neoantigens, which are expressed on tumor cells, are one of the main targets of an effective antitumor T-cell response. Cancer immunotherapies to target neoantigens are of growing interest and are in early human trials, but methods to identify neoantigens either require invasive or difficult-to-obtain clinical specimens, require the screening of hundreds to thousands of synthetic peptides or tandem minigenes, or are only relevant to specific human leukocyte antigen (HLA) alleles. We apply deep learning to a large (N = 74 patients) HLA peptide and genomic dataset from various human tumors to create a computational model of antigen presentation for neoantigen prediction...
December 17, 2018: Nature Biotechnology
Avinash Kumar Thakur, Liviu Movileanu
Protein-protein interactions (PPIs) are essential for many cellular processes. However, transient PPIs are difficult to measure at high throughput or in complex biological fluids using existing methods. We engineered a genetically encoded sensor for real-time sampling of transient PPIs at single-molecule resolution. Our sensor comprises a truncated outer membrane protein pore, a flexible tether, a protein receptor and a peptide adaptor. When a protein ligand present in solution binds to the receptor, reversible capture and release events of the receptor can be measured as current transitions between two open substates of the pore...
December 10, 2018: Nature Biotechnology
Etienne Becht, Leland McInnes, John Healy, Charles-Antoine Dutertre, Immanuel W H Kwok, Lai Guan Ng, Florent Ginhoux, Evan W Newell
Advances in single-cell technologies have enabled high-resolution dissection of tissue composition. Several tools for dimensionality reduction are available to analyze the large number of parameters generated in single-cell studies. Recently, a nonlinear dimensionality-reduction technique, uniform manifold approximation and projection (UMAP), was developed for the analysis of any type of high-dimensional data. Here we apply it to biological data, using three well-characterized mass cytometry and single-cell RNA sequencing datasets...
December 3, 2018: Nature Biotechnology
Felicity Allen, Luca Crepaldi, Clara Alsinet, Alexander J Strong, Vitalii Kleshchevnikov, Pietro De Angeli, Petra Páleníková, Anton Khodak, Vladimir Kiselev, Michael Kosicki, Andrew R Bassett, Heather Harding, Yaron Galanty, Francisco Muñoz-Martínez, Emmanouil Metzakopian, Stephen P Jackson, Leopold Parts
The DNA mutation produced by cellular repair of a CRISPR-Cas9-generated double-strand break determines its phenotypic effect. It is known that the mutational outcomes are not random, but depend on DNA sequence at the targeted location. Here we systematically study the influence of flanking DNA sequence on repair outcome by measuring the edits generated by >40,000 guide RNAs (gRNAs) in synthetic constructs. We performed the experiments in a range of genetic backgrounds and using alternative CRISPR-Cas9 reagents...
November 27, 2018: Nature Biotechnology
Bo Xu, Rui Ma, Luke Russell, Ji Young Yoo, Jianfeng Han, Hanwei Cui, Ping Yi, Jianying Zhang, Hiroshi Nakashima, Hongsheng Dai, E Antonio Chiocca, Balveen Kaur, Michael A Caligiuri, Jianhua Yu
The efficacy of oncolytic herpes simplex virus (oHSV) is limited by rapid viral clearance by innate immune effector cells and poor intratumoral viral spread. We combine two approaches to overcome these barriers: inhibition of natural killer (NK) cells and enhancement of intratumoral viral spread. We engineered an oHSV to express CDH1, encoding E-cadherin, an adherent molecule and a ligand for KLRG1, an inhibitory receptor expressed on NK cells. In vitro, infection with this engineered virus, named OV-CDH1, induced high surface E-cadherin expression on infected glioblastoma (GBM) cells, which typically lack endogenous E-cadherin...
November 26, 2018: Nature Biotechnology
Amalie K Bentzen, Lina Such, Kamilla K Jensen, Andrea M Marquard, Leon E Jessen, Natalie J Miller, Candice D Church, Rikke Lyngaa, David M Koelle, Jürgen C Becker, Carsten Linnemann, Ton N M Schumacher, Paolo Marcatili, Paul Nghiem, Morten Nielsen, Sine R Hadrup
The promiscuous nature of T-cell receptors (TCRs) allows T cells to recognize a large variety of pathogens, but makes it challenging to understand and control T-cell recognition. Existing technologies provide limited information about the key requirements for T-cell recognition and the ability of TCRs to cross-recognize structurally related elements. Here we present a 'one-pot' strategy for determining the interactions that govern TCR recognition of peptide-major histocompatibility complex (pMHC). We measured the relative affinities of TCRs to libraries of barcoded peptide-MHC variants and applied this knowledge to understand the recognition motif, here termed the TCR fingerprint...
November 19, 2018: Nature Biotechnology
Brett B Maricque, Hemangi G Chaudhari, Barak A Cohen
A gene's position in the genome can profoundly affect its expression because regional differences in chromatin modulate the activity of locally acting cis-regulatory sequences (CRSs). Here we study how CRSs and regional chromatin act in concert on a genome-wide scale. We present a massively parallel reporter gene assay that measures the activities of hundreds of different CRSs, each integrated at many specific genomic locations. Although genome location strongly affected CRS activity, the relative strengths of CRSs were maintained at all chromosomal locations...
November 19, 2018: Nature Biotechnology
Anton A Turanov, Agnes Lo, Matthew R Hassler, Angela Makris, Ami Ashar-Patel, Julia F Alterman, Andrew H Coles, Reka A Haraszti, Loic Roux, Bruno M D C Godinho, Dimas Echeverria, Suzanne Pears, Jim Iliopoulos, Renuka Shanmugalingam, Robert Ogle, Zsuzsanna K Zsengeller, Annemarie Hennessy, S Ananth Karumanchi, Melissa J Moore, Anastasia Khvorova
Preeclampsia is a placentally induced hypertensive disorder of pregnancy that is associated with substantial morbidity and mortality to mothers and fetuses. Clinical manifestations of preterm preeclampsia result from excess circulating soluble vascular endothelial growth factor receptor FLT1 (sFLT1 or sVEGFR1) of placental origin. Here we identify short interfering RNAs (siRNAs) that selectively silence the three sFLT1 mRNA isoforms primarily responsible for placental overexpression of sFLT1 without reducing levels of full-length FLT1 mRNA...
November 19, 2018: Nature Biotechnology
Shu-Qi Zhang, Ke-Yue Ma, Alexandra A Schonnesen, Mingliang Zhang, Chenfeng He, Eric Sun, Chad M Williams, Weiping Jia, Ning Jiang
We present tetramer-associated T-cell receptor sequencing (TetTCR-seq) to link T cell receptor (TCR) sequences to their cognate antigens in single cells at high throughput. Binding is determined using a library of DNA-barcoded antigen tetramers that is rapidly generated by in vitro transcription and translation. We applied TetTCR-seq to identify patterns in TCR cross-reactivity with cancer neoantigens and to rapidly isolate neoantigen-specific TCRs with no cross-reactivity to the wild-type antigen.
November 12, 2018: Nature Biotechnology
Sara H Rouhanifard, Ian A Mellis, Margaret Dunagin, Sareh Bayatpour, Connie L Jiang, Ian Dardani, Orsolya Symmons, Benjamin Emert, Eduardo Torre, Allison Cote, Alessandra Sullivan, John A Stamatoyannopoulos, Arjun Raj
Methods for detecting single nucleic acids in cell and tissues, such as fluorescence in situ hybridization (FISH), are limited by relatively low signal intensity and nonspecific probe binding. Here we present click-amplifying FISH (clampFISH), a method for fluorescence detection of nucleic acids that achieves high specificity and high-gain (>400-fold) signal amplification. ClampFISH probes form a 'C' configuration upon hybridization to the sequence of interest in a double helical manner. The ends of the probes are ligated together using bio-orthogonal click chemistry, effectively locking the probes around the target...
November 12, 2018: Nature Biotechnology
Ying Liu, Zhongzheng Cao, Yinan Wang, Yu Guo, Ping Xu, Pengfei Yuan, Zhiheng Liu, Yuan He, Wensheng Wei
The functions of many long noncoding RNAs (lncRNAs) in the human genome remain unknown owing to the lack of scalable loss-of-function screening tools. We previously used pairs of CRISPR-Cas9 (refs. 1, 2, 3) single guide RNAs (sgRNAs) for small-scale functional screening of lncRNAs. Here we demonstrate genome-wide screening of lncRNA function using sgRNAs to target splice sites and achieve exon skipping or intron retention. Splice-site targeting outperformed a conventional CRISPR library in a negative selection screen targeting 79 ribosomal genes...
November 5, 2018: Nature Biotechnology
Qian Zhu, Sheel Shah, Ruben Dries, Long Cai, Guo-Cheng Yuan
How intrinsic gene-regulatory networks interact with a cell's spatial environment to define its identity remains poorly understood. We developed an approach to distinguish between intrinsic and extrinsic effects on global gene expression by integrating analysis of sequencing-based and imaging-based single-cell transcriptomic profiles, using cross-platform cell type mapping combined with a hidden Markov random field model. We applied this approach to dissect the cell-type- and spatial-domain-associated heterogeneity in the mouse visual cortex region...
October 29, 2018: Nature Biotechnology
Charlotte Harrison
No abstract text is available yet for this article.
January 3, 2019: Nature Biotechnology
(no author information available yet)
No abstract text is available yet for this article.
January 3, 2019: Nature Biotechnology
Jessica M Stringer, Patrick S Western
No abstract text is available yet for this article.
January 3, 2019: Nature Biotechnology
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