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Unconventional γδ T cells ‘the new black’ in cancer therapy
Elie DolginÂÂ
Topical herpesvirus gene therapy enters final lap
Cormac SheridanÂÂ
An open invitation to the Understudied Proteins Initiative
Georg Kustatscher, Tom Collins, Anne-Claude Gingras, Tiannan Guo, Henning Hermjakob, Trey Ideker, Kathryn S. Lilley, Emma Lundberg, Edward M. Marcotte, Markus Ralser & Juri RappsilberÂ
The GA4GH Phenopacket schema defines a computable representation of clinical data
Julius O. B. Jacobsen, Michael Baudis, Gareth S. Baynam, Jacques S. Beckmann, Sergi Beltran, Orion J. Buske, Tiffany J. Callahan, Christopher G. Chute, Mélanie Courtot, Daniel Danis, Olivier Elemento, Andrea Essenwanger, Robert R. Freimuth, Michael A. Gargano, Tudor Groza, Ada Hamosh, Nomi L. Harris, Rajaram Kaliyaperumal, Kevin C. Kent Lloyd, Aly Khalifa, Peter M. Krawitz, Sebastian Köhler, Brian J. Laraway, Heikki Lehväslaiho, The GAGH Phenopacket Modeling Consortium, …Peter N. RobinsonÂ
The Worldview national ranking of health biotech sectors
John Hodgson & Deanna Schreiber-GregoryÂ
Vascepa patents under legal scrutiny
Gregory Curfman & Justin ColeÂ
Antibiotic discovery with machine learning
Cesar de la Fuente-NunezÂÂ
Pathogenic or benign?
Peter P. Du, Katherine Liu, Michael C. Bassik & Gaelen T. HessÂ
Identification of antimicrobial peptides from the human gut microbiome using deep learning
The clinical progress of mRNA vaccines and immunotherapies
Ann J. Barbier, Allen Yujie Jiang, Peng Zhang, Richard Wooster & Daniel G. AndersonÂ
doi : 10.1038/s41587-022-01294-2
The emergency use authorizations (EUAs) of two mRNA-based severe acute respiratory syndrome coronavirus (SARS-CoV)-2 vaccines approximately 11 months after publication of the viral sequence highlights the transformative potential of this nucleic acid technology.
Cell types of origin of the cell-free transcriptome
Sevahn K. Vorperian, Mira N. Moufarrej, Tabula Sapiens Consortium & Stephen R. QuakeÂ
doi : 10.1038/s41587-021-01188-9
Cell-free RNA from liquid biopsies can be analyzed to determine disease tissue of origin. We extend this concept to identify cell types of origin using the Tabula Sapiens transcriptomic cell atlas as well as individual tissue transcriptomic cell atlases in combination with the Human Protein Atlas RNA consensus dataset. We define cell type signature scores, which allow the inference of cell types that contribute to cell-free RNA for a variety of diseases.
Base editing sensor libraries for high-throughput engineering and functional analysis of cancer-associated single nucleotide variants
Francisco J. Sánchez-Rivera, Bianca J. Diaz, Edward R. Kastenhuber, Henri Schmidt, Alyna Katti, Margaret Kennedy, Vincent Tem, Yu-Jui Ho, Josef Leibold, Stella V. Paffenholz, Francisco M. Barriga, Kevan Chu, Sukanya Goswami, Alexandra N. Wuest, Janelle M. Simon, Kaloyan M. Tsanov, Debyani Chakravarty, Hongxin Zhang, Christina S. Leslie, Scott W. Lowe & Lukas E. DowÂ
doi : 10.1038/s41587-021-01172-3
Base editing can be applied to characterize single nucleotide variants of unknown function, yet defining effective combinations of single guide RNAs (sgRNAs) and base editors remains challenging.
High-throughput functional evaluation of human cancer-associated mutations using base editors
Younggwang Kim, Seungho Lee, Soohyuk Cho, Jinman Park, Dongwoo Chae, Taeyoung Park, John D. Minna & Hyongbum Henry KimÂ
doi : 10.1038/s41587-022-01276-4
Comprehensive phenotypic characterization of the many mutations found in cancer tissues is one of the biggest challenges in cancer genomics. In this study, we evaluated the functional effects of 29,060 cancer-related transition mutations that result in protein variants on the survival and proliferation of non-tumorigenic lung cells using cytosine and adenine base editors and single guide RNA (sgRNA) libraries.
Saturation variant interpretation using CRISPR prime editing
Steven Erwood, Teija M. I. Bily, Jason Lequyer, Joyce Yan, Nitya Gulati, Reid A. Brewer, Liangchi Zhou, Laurence Pelletier, Evgueni A. Ivakine & Ronald D. CohnÂ
doi : 10.1038/s41587-021-01201-1
High-throughput functional characterization of genetic variants in their endogenous locus has so far been possible only with methods that rely on homology-directed repair, which are limited by low editing efficiencies.
Massively parallel phenotyping of coding variants in cancer with Perturb-seq
Oana Ursu, James T. Neal, Emily Shea, Pratiksha I. Thakore, Livnat Jerby-Arnon, Lan Nguyen, Danielle Dionne, Celeste Diaz, Julia Bauman, Mariam Mounir Mosaad, Christian Fagre, April Lo, Maria McSharry, Andrew O. Giacomelli, Seav Huong Ly, Orit Rozenblatt-Rosen, William C. Hahn, Andrew J. Aguirre, Alice H. Berger, Aviv Regev & Jesse S. BoehmÂ
doi : 10.1038/s41587-021-01160-7
Genome sequencing studies have identified millions of somatic variants in cancer, but it remains challenging to predict the phenotypic impact of most. Experimental approaches to distinguish impactful variants often use phenotypic assays that report on predefined gene-specific functional effects in bulk cell populations.
A humanized mouse model of chronic COVID-19
Esen Sefik, Benjamin Israelow, Haris Mirza, Jun Zhao, Rihao Qu, Eleanna Kaffe, Eric Song, Stephanie Halene, Eric Meffre, Yuval Kluger, Michel Nussenzweig, Craig B. Wilen, Akiko Iwasaki & Richard A. FlavellÂ
doi : 10.1038/s41587-021-01155-4
Coronavirus disease 2019 (COVID-19) is an infectious disease that can present as an uncontrolled, hyperactive immune response, causing severe immunological injury. Existing rodent models do not recapitulate the sustained immunopathology of patients with severe disease.
Identification of antimicrobial peptides from the human gut microbiome using deep learning
Yue Ma, Zhengyan Guo, Binbin Xia, Yuwei Zhang, Xiaolin Liu, Ying Yu, Na Tang, Xiaomei Tong, Min Wang, Xin Ye, Jie Feng, Yihua Chen & Jun WangÂ
doi : 10.1038/s41587-022-01226-0
The human gut microbiome encodes a large variety of antimicrobial peptides (AMPs), but the short lengths of AMPs pose a challenge for computational prediction.
Using deep learning to annotate the protein universe
Maxwell L. Bileschi, David Belanger, Drew H. Bryant, Theo Sanderson, Brandon Carter, D. Sculley, Alex Bateman, Mark A. DePristo & Lucy J. ColwellÂ
doi : 10.1038/s41587-021-01179-w
Understanding the relationship between amino acid sequence and protein function is a long-standing challenge with far-reaching scientific and translational implications. State-of-the-art alignment-based techniques cannot predict function for one-third of microbial protein sequences, hampering our ability to exploit data from diverse organisms.
Efficient in vitro and in vivo RNA editing via recruitment of endogenous ADARs using circular guide RNAs
Dhruva Katrekar, James Yen, Yichen Xiang, Anushka Saha, Dario Meluzzi, Yiannis Savva & Prashant MaliÂ
doi : 10.1038/s41587-021-01171-4
Recruiting endogenous adenosine deaminases using exogenous guide RNAs to edit cellular RNAs is a promising therapeutic strategy, but editing efficiency and durability remain low using current guide RNA designs.
Engineered circular ADAR-recruiting RNAs increase the efficiency and fidelity of RNA editing in vitro and in vivo
Zongyi Yi, Liang Qu, Huixian Tang, Zhiheng Liu, Ying Liu, Feng Tian, Chunhui Wang, Xiaoxue Zhang, Ziqi Feng, Ying Yu, Pengfei Yuan, Zexuan Yi, Yanxia Zhao & Wensheng WeiÂ
doi : 10.1038/s41587-021-01180-3
Current methods for programmed RNA editing using endogenous ADAR enzymes and engineered ADAR-recruiting RNAs (arRNAs) suffer from low efficiency and bystander off-target editing. Here, we describe LEAPER 2.0, an updated version of LEAPER that uses covalently closed circular arRNAs, termed circ-arRNAs.
Development of spirulina for the manufacture and oral delivery of protein therapeutics
Benjamin W. Jester, Hui Zhao, Mesfin Gewe, Thomas Adame, Lisa Perruzza, David T. Bolick, Jan Agosti, Nhi Khuong, Rolf Kuestner, Caitlin Gamble, Kendra Cruickshank, Jeremy Ferrara, Rachelle Lim, Troy Paddock, Colin Brady, Stacey Ertel, Miaohua Zhang, Alex Pollock, Jamie Lee, Jian Xiong, Michael Tasch, Tracy Saveria, David Doughty, Jacob Marshall, …James RobertsÂ
doi : 10.1038/s41587-022-01249-7
The use of the edible photosynthetic cyanobacterium Arthrospira platensis (spirulina) as a biomanufacturing platform has been limited by a lack of genetic tools.
Imaging of innate immunity activation in vivo with a redox-tuned PET reporter
Federica Pisaneschi, Seth T. Gammon, Vincenzo Paolillo, Sarah A. Qureshy & David Piwnica-WormsÂ
doi : 10.1038/s41587-021-01169-y
High-redox-potential reactive oxygen species and reactive nitrogen species (ROS/RNS), generated by NADPH oxidase-2 (NOX2), myeloperoxidase (MPO) and related enzymes, are key effector molecules of innate immunity.
Author Correction: Development of spirulina for the manufacture and oral delivery of protein therapeutics
Benjamin W. Jester, Hui Zhao, Mesfin Gewe, Thomas Adame, Lisa Perruzza, David T. Bolick, Jan Agosti, Nhi Khuong, Rolf Kuestner, Caitlin Gamble, Kendra Cruickshank, Jeremy Ferrara, Rachelle Lim, Troy Paddock, Colin Brady, Stacey Ertel, Miaohua Zhang, Alex Pollock, Jamie Lee, Jian Xiong, Michael Tasch, Tracy Saveria, David Doughty, Jacob Marshall, …James RobertsÂ
Publisher Correction: Cell types of origin of the cell-free transcriptome
Sevahn K. Vorperian, Mira N. Moufarrej, Tabula Sapiens Consortium & Stephen R. QuakeÂ
A virtual innovation bootcamp to remotely connect and empower students to solve COVID-19-related medical problems
Mario V. Russo, Abhinav J. Appukutty, Aadit P. Shah, Harsha K. Mohan, Andy G. S. Daniel, Andrew Pack & Richard XieÂ
