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The next giant step for microbes

doi : 10.1038/s41587-022-01655-x

Volume 41 Issue 1, January 2023

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Illumina faces short-read rivals

Michael Eisenstein 

doi : 10.1038/s41587-022-01632-4

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UK launches whole-genome sequencing pilot for babies

doi : 10.1038/s41587-022-01644-0

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Chikungunya and Lyme vaccines make headway

doi : 10.1038/s41587-022-01641-3

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Drug for delaying diabetes wins landmark approval

Elie Dolgin 

doi : 10.1038/s41587-022-01633-3

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Chicken from cells is safe to eat, says FDA

doi : 10.1038/d41587-022-00018-w

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Exploring the value of a global gene drive project registry

Riley I. Taitingfong, Cynthia Triplett, Váleri N. Vásquez, Ramya M. Rajagopalan, Robyn Raban, Aaron Roberts, Gerard Terradas, Bridget Baumgartner, Claudia Emerson, Fred Gould, Fredros Okumu, Cynthia E. Schairer, Hervé C. Bossin, Leah Buchman, Karl J. Campbell, Anna Clark, Jason Delborne, Kevin Esvelt, Joshua Fisher, Robert M. Friedman, Gigi Gronvall, Nikos Gurfield, Elizabeth Heitman, Natalie Kofler, …Cinnamon S. BlossÂ

doi : 10.1038/s41587-022-01591-w

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Intellectual property and assisted reproductive technology

David Cyranoski, Jorge L. Contreras & Victoria T. CarringtonÂ

doi : 10.1038/s41587-022-01592-9

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Transfer of a plant-derived photosynthetic system to mammalian cells

Anne Doerr 

doi : 10.1038/s41587-022-01645-z

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Measuring elusive protein complexes in single cells

Barbara Cheifet 

doi : 10.1038/s41587-022-01646-y

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Linking genetic variants to cellular function and disease

Alexandra DespangÂ

doi : 10.1038/s41587-022-01647-x

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Framework for multiplicative scaling of single-cell proteomics

doi : 10.1038/s41587-022-01411-1

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Accessible bioengineered corneal tissue to address a blinding disease globally

doi : 10.1038/s41587-022-01409-9

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Normalizing cancer RNA-seq data for library size, tumor purity and batch effects

doi : 10.1038/s41587-022-01441-9

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Engineered Cas13 variants with minimal collateral RNA targeting

doi : 10.1038/s41587-022-01423-x

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BEHAV3D: an imaging and transcriptomics platform that unravels T cell antitumor activity

doi : 10.1038/s41587-022-01398-9

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Prediction of peptide mass spectral libraries with machine learning

Jürgen Cox 

doi : 10.1038/s41587-022-01424-w

The recent development of machine learning methods to identify peptides in complex mass spectrometric data constitutes a major breakthrough in proteomics.

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Automated reconstruction of whole-embryo cell lineages by learning from sparse annotations

Caroline Malin-Mayor, Peter Hirsch, Leo Guignard, Katie McDole, Yinan Wan, William C. Lemon, Dagmar Kainmueller, Philipp J. Keller, Stephan Preibisch & Jan FunkeÂ

doi : 10.1038/s41587-022-01427-7

We present a method to automatically identify and track nuclei in time-lapse microscopy recordings of entire developing embryos. The method combines deep learning and global optimization. On a mouse dataset, it reconstructs 75.8% of cell lineages spanning 1 h, as compared to 31.8% for the competing method. Our approach improves understanding of where and when cell fate decisions are made in developing embryos, tissues, and organs.

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Increasing the throughput of sensitive proteomics by plexDIA

Jason Derks, Andrew Leduc, Georg Wallmann, R. Gray Huffman, Matthew Willetts, Saad Khan, Harrison Specht, Markus Ralser, Vadim Demichev & Nikolai SlavovÂ

doi : 10.1038/s41587-022-01389-w

Current mass spectrometry methods enable high-throughput proteomics of large sample amounts, but proteomics of low sample amounts remains limited in depth and throughput. To increase the throughput of sensitive proteomics, we developed an experimental and computational framework, called plexDIA, for simultaneously multiplexing the analysis of peptides and samples.

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Uncovering the mode of action of engineered T cells in patient cancer organoids

Johanna F. Dekkers, Maria Alieva, Astrid Cleven, Farid Keramati, Amber K. L. Wezenaar, Esmée J. van Vliet, Jens Puschhof, Peter Brazda, Inez Johanna, Angelo D. Meringa, Heggert G. Rebel, Maj-Britt Buchholz, Mario Barrera Román, Amber L. Zeeman, Sam de Blank, Domenico Fasci, Maarten H. Geurts, Annelisa M. Cornel, Else Driehuis, Rosemary Millen, Trudy Straetemans, Mara J. T. Nicolasen, Tineke Aarts-Riemens, Hendrikus C. R. Ariese, …Anne C. RiosÂ

doi : 10.1038/s41587-022-01397-w

Extending the success of cellular immunotherapies against blood cancers to the realm of solid tumors will require improved in vitro models that reveal therapeutic modes of action at the molecular level. Here we describe a system, called BEHAV3D, developed to study the dynamic interactions of immune cells and patient cancer organoids by means of imaging and transcriptomics.

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Bioengineered corneal tissue for minimally invasive vision restoration in advanced keratoconus in two clinical cohorts

Mehrdad Rafat, Mahmoud Jabbarvand, Namrata Sharma, Maria Xeroudaki, Shideh Tabe, Raha Omrani, Muthukumar Thangavelu, Anthony Mukwaya, Per Fagerholm, Anton Lennikov, Farshad Askarizadeh & Neil LagaliÂ

doi : 10.1038/s41587-022-01408-w

Visual impairment from corneal stromal disease affects millions worldwide. We describe a cell-free engineered corneal tissue, bioengineered porcine construct, double crosslinked (BPCDX) and a minimally invasive surgical method for its implantation.

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Removing unwanted variation from large-scale RNA sequencing data with PRPS

Ramyar Molania, Momeneh Foroutan, Johann A. Gagnon-Bartsch, Luke C. Gandolfo, Aryan Jain, Abhishek Sinha, Gavriel Olshansky, Alexander Dobrovic, Anthony T. Papenfuss & Terence P. SpeedÂ

doi : 10.1038/s41587-022-01440-w

Accurate identification and effective removal of unwanted variation is essential to derive meaningful biological results from RNA sequencing (RNA-seq) data, especially when the data come from large and complex studies.

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High-throughput continuous evolution of compact Cas9 variants targeting single-nucleotide-pyrimidine PAMs

Tony P. Huang, Zachary J. Heins, Shannon M. Miller, Brandon G. Wong, Pallavi A. Balivada, Tina Wang, Ahmad S. Khalil & David R. LiuÂ

doi : 10.1038/s41587-022-01410-2

Despite the availability of Cas9 variants with varied protospacer-adjacent motif (PAM) compatibilities, some genomic loci�especially those with pyrimidine-rich PAM sequences�remain inaccessible by high-activity Cas9 proteins.

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High-fidelity Cas13 variants for targeted RNA degradation with minimal collateral effects

Huawei Tong, Jia Huang, Qingquan Xiao, Bingbing He, Xue Dong, Yuanhua Liu, Xiali Yang, Dingyi Han, Zikang Wang, Xuchen Wang, Wenqin Ying, Runze Zhang, Yu Wei, Chunlong Xu, Yingsi Zhou, Yanfei Li, Minqing Cai, Qifang Wang, Mingxing Xue, Guoling Li, Kailun Fang, Hainan Zhang & Hui YangÂ

doi : 10.1038/s41587-022-01419-7

CRISPR–Cas13 systems have recently been used for targeted RNA degradation in various organisms. However, collateral degradation of bystander RNAs has limited their in vivo applications. Here, we design a dual-fluorescence reporter system for detecting collateral effects and screening Cas13 variants in mammalian cells.

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The role of transposon inverted repeats in balancing drought tolerance and yield-related traits in maize

Xiaopeng Sun, Yanli Xiang, Nannan Dou, Hui Zhang, Surui Pei, Arcadio Valdes Franco, Mitra Menon, Brandon Monier, Taylor Ferebee, Tao Liu, Sanyang Liu, Yuchi Gao, Jubin Wang, William Terzaghi, Jianbing Yan, Sarah Hearne, Lin Li, Feng Li & Mingqiu DaiÂ

doi : 10.1038/s41587-022-01470-4

The genomic basis underlying the selection for environmental adaptation and yield-related traits in maize remains poorly understood. Here we carried out genome-wide profiling of the small RNA (sRNA) transcriptome (sRNAome) and transcriptome landscapes of a global maize diversity panel under dry and wet conditions and uncover dozens of environment-specific regulatory hotspots.

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A comprehensive SARS-CoV-2–human protein–protein interactome reveals COVID-19 pathobiology and potential host therapeutic targets

Yadi Zhou, Yuan Liu, Shagun Gupta, Mauricio I. Paramo, Yuan Hou, Chengsheng Mao, Yuan Luo, Julius Judd, Shayne Wierbowski, Marta Bertolotti, Mriganka Nerkar, Lara Jehi, Nir Drayman, Vlad Nicolaescu, Haley Gula, SavaÅŸ Tay, Glenn Randall, Peihui Wang, John T. Lis, Cédric Feschotte, Serpil C. Erzurum, Feixiong Cheng & Haiyuan YuÂ

doi : 10.1038/s41587-022-01474-0

Studying viral–host protein–protein interactions can facilitate the discovery of therapies for viral infection. We use high-throughput yeast two-hybrid experiments and mass spectrometry to generate a comprehensive SARS-CoV-2–human protein–protein interactome network consisting of 739 high-confidence binary and co-complex interactions, validating 218 known SARS-CoV-2 host factors and revealing 361 novel ones.

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A proteome-scale map of the SARS-CoV-2–human contactome

Dae-Kyum Kim, Benjamin Weller, Chung-Wen Lin, Dayag Sheykhkarimli, Jennifer J. Knapp, Guillaume Dugied, Andreas Zanzoni, Carles Pons, Marie J. Tofaute, Sibusiso B. Maseko, Kerstin Spirohn, Florent Laval, Luke Lambourne, Nishka Kishore, Ashyad Rayhan, Mayra Sauer, Veronika Young, Hridi Halder, Nora Marín-de la Rosa, Oxana Pogoutse, Alexandra Strobel, Patrick Schwehn, Roujia Li, Simin T. Rothballer, …Pascal Falter-BraunÂ

doi : 10.1038/s41587-022-01475-z

Understanding the mechanisms of coronavirus disease 2019 (COVID-19) disease severity to efficiently design therapies for emerging virus variants remains an urgent challenge of the ongoing pandemic. Infection and immune reactions are mediated by direct contacts between viral molecules and the host proteome, and the vast majority of these virus–host contacts (the ‘contactome’) have not been identified.

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Author Correction: m6A RNA modifications are measured at single-base resolution across the mammalian transcriptome

Lulu Hu, Shun Liu, Yong Peng, Ruiqi Ge, Rui Su, Chamara Senevirathne, Bryan T. Harada, Qing Dai, Jiangbo Wei, Lisheng Zhang, Ziyang Hao, Liangzhi Luo, Huanyu Wang, Yuru Wang, Minkui Luo, Mengjie Chen, Jianjun Chen & Chuan HeÂ

doi : 10.1038/s41587-022-01616-4

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Increasing the success potential of promising biotech companies

Stephanie K. Marrus & John A. BlahoÂ

doi : 10.1038/s41587-022-01627-1

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