Article
Multidisciplinary Sciences
Martin Pacesa, Luuk Loeff, Irma Querques, Lena M. Muckenfuss, Marta Sawicka, Martin Jinek
Summary: Researchers have used cryo-electron microscopy to observe the structural changes that occur during the binding and activation of Cas9. These findings provide a valuable structural framework for understanding the conformational checkpoint mechanism of Cas9 and may guide the development of new Cas9 variants and guide RNA designs with enhanced specificity and activity.
Article
Biochemistry & Molecular Biology
Mengjiao Su, Fan Li, Yujue Wang, Yan Gao, Weiqi Lan, Zhiwei Shao, Chen Zhu, Na Tang, Jianhua Gan, Zhaowei Wu, Quanjiang Ji
Summary: Researchers have discovered a rare C-rich PAM-specific Cas12f nuclease, CnCas12f1, which can be used as a genome editor in human cells. Through structural and engineering studies, they have gained insights into its working mechanism and expanded the mini-CRISPR toolbox.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Kunpeng Lu, Yifei Pan, Jianghong Shen, Lin Yang, Chengyu Zhan, Shubo Liang, Shuaishuai Tai, Linrong Wan, Tian Li, Tingcai Cheng, Bi Ma, Guoqing Pan, Ningjia He, Cheng Lu, Eric Westhof, Zhonghuai Xiang, Min-Jin Han, Xiaoling Tong, Fangyin Dai
Summary: SilkMeta is a comprehensive database that covers the silkworm's pan-genome and multi-omics data, providing useful strategies and data for comparative and functional genomics research.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Hillary Koch, Cheryl A. Keller, Guanjue Xiang, Belinda Giardine, Feipeng Zhang, Yicheng Wang, Ross C. Hardison, Qunhua Li
Summary: Comparing experimental results across multiple different conditions can be more precise and meaningful. Researchers have introduced a method called CLIMB that allows for this type of comparison and captures interpretable and biologically meaningful information.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Wenlong Zhu, Stuart McQuarrie, Sabine Gruschow, Stephen A. McMahon, Shirley Graham, Tracey M. Gloster, Malcolm F. White
Summary: A newly discovered CARF family effector named Can2 is found to provide effective immunity against plasmid transformation and bacteriophage infection in Escherichia coli by being activated by cyclic tetra-adenylate (cA(4)) and displaying both DNase and RNase activity. The structure of Can2 in complex with cA(4) reveals a potential mechanism for the cA(4)-mediated activation of the enzyme, where an active site cleft is exposed upon activator binding. These findings enhance our understanding of type III CRISPR cOA signaling and effector function.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Multidisciplinary Sciences
Greta Bigelyte, Joshua K. Young, Tautvydas Karvelis, Karolina Budre, Rimante Zedaveinyte, Vesna Djukanovic, Elizabeth Van Ginkel, Sushmitha Paulraj, Stephen Gasior, Spencer Jones, Lanie Feigenbutz, Grace St Clair, Pierluigi Barone, Jennifer Bohn, Ananta Acharya, Gina Zastrow-Hayes, Selgar Henkel-Heinecke, Arunas Silanskas, Ralf Seidel, Virginijus Siksnys
Summary: Class 2 CRISPR systems have diverse effector proteins, with some miniature Cas12f nucleases showing potential for targeted DNA modification in both plant and human cells. The compact size and efficient activity of these Cas12f effectors make them promising tools for in vivo genome editing applications. Biochemical characterization of SpCas12f1 demonstrates its functionality in creating targeted modifications, particularly in plants with short heat pulses.
NATURE COMMUNICATIONS
(2021)
Article
Engineering, Civil
Asma Belhadi, Youcef Djenouri, Gautam Srivastava, Alberto Cano, Jerry Chun-Wei Lin
Summary: This research proposed a novel hybrid framework for identifying group anomaly detection from sequence data, utilizing data mining-based and GPU-based approaches, and experiments showed that both methods outperformed baseline methods for group detection.
IEEE TRANSACTIONS ON INTELLIGENT TRANSPORTATION SYSTEMS
(2022)
Article
Multidisciplinary Sciences
Liyang Zhang, John A. Zuris, Ramya Viswanathan, Jasmine N. Edelstein, Rolf Turk, Bernice Thommandru, H. Tomas Rube, Steve E. Glenn, Michael A. Collingwood, Nicole M. Bode, Sarah F. Beaudoin, Swarali Lele, Sean N. Scott, Kevin M. Wasko, Steven Sexton, Christopher M. Borges, Mollie S. Schubert, Gavin L. Kurgan, Matthew S. McNeill, Cecilia A. Fernandez, Vic E. Myer, Richard A. Morgan, Mark A. Behlke, Christopher A. Vakulskas
Summary: AsCas12a Ultra is an engineered variant with high editing efficiency and on-target specificity, making it ideal for complex therapeutic genome editing applications in multiple cell types.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Stamatis Papathanasiou, Styliani Markoulaki, Logan J. Blaine, Mitchell L. Leibowitz, Cheng-Zhong Zhang, Rudolf Jaenisch, David Pellman
Summary: The study tracks aberrations in karyotypes during embryonic development post-Cas9 editing, revealing unwanted on-target complications including major chromosome structural alterations like whole chromosome loss. Micronuclei and chromosome bridges are observed as consequences of mitosis errors, contributing to these common karyotype aberrations after Cas9 treatment in embryos.
NATURE COMMUNICATIONS
(2021)
Article
Computer Science, Information Systems
Chunkai Zhang, Zilin Du, Yuting Yang, Wensheng Gan, Philip S. Yu
Summary: In this study, the problem of on-shelf utility mining (OSUM) was introduced and two methods (OSUMS and OSUMS+) were proposed to extract high-utility sequential patterns. Efforts were made to improve efficiency through strategies and data structures, with substantial experimental results showing the superiority of these methods.
ACM TRANSACTIONS ON KNOWLEDGE DISCOVERY FROM DATA
(2022)
Review
Genetics & Heredity
Bonnie Berger, Yun William Yu
Summary: Genome sequencing and analysis decode functional information in DNA sequences and study cell variations. The increasing throughput of sequencing platforms has led to computational challenges in analyzing the large amount of raw data produced. Recent methodological advances offer solutions but also introduce trade-offs, such as accuracy and memory, expense and time, and the need for expertise in non-standard programming interfaces and complex infrastructure.
NATURE REVIEWS GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Karthik Murugan, Shravanti K. Suresh, Arun S. Seetharam, Andrew J. Severin, Dipali G. Sashital
Summary: Cas9 variants differ in their cleavage rates and ability to create double-strand breaks at targets with multiple mismatches, which may contribute to the variations in specificities observed in genome editing studies.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biotechnology & Applied Microbiology
Jin Zhou, Peng Chen, Hongjian Wang, Huan Liu, Yongzheng Li, Youpeng Zhang, Yankang Wu, Chonil Paek, Zaiqiao Sun, Jun Lei, Lei Yin
Summary: Researchers have engineered variants of Cas12a enzyme, Lb-K538R and Lb2-K518R, with more stringent PAM recognition and lower off-target effects. These variants showed high gene editing activity and enabled the selection of potential target sites with lower off-target effects. The study also suggests that Cas proteins can be designed to reduce off-target effects by stringent PAM recognition, providing a promising and practical approach for genome editing.
Article
Biochemistry & Molecular Biology
David M. L. Picton, Yvette A. Luyten, Richard D. Morgan, Andrew Nelson, Darren L. Smith, David T. F. Dryden, Jay C. D. Hinton, Tim R. Blower
Summary: Bacteria have evolved various systems to defend against bacteriophages and mobile genetic elements, with genes often clustered in defense islands. Functional characterization of a defense island in a multidrug resistant plasmid of E. fergusonii has revealed a novel GmrSD-family type IV DNA modification-dependent restriction enzyme, BrxU, that provides robust phage protection. The study also presents the first structure of BrxU and demonstrates its ability to cleave a range of modified DNAs through a multi-step reaction cycle.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Multidisciplinary Sciences
Zhenyu Zhang, Kyle Hernandez, Jeremiah Savage, Shenglai Li, Dan Miller, Stuti Agrawal, Francisco Ortuno, Louis M. Staudt, Allison Heath, Robert L. Grossman
Summary: The goal of National Cancer Institute's Genomic Data Commons (GDC) is to provide the cancer research community with a data repository of uniformly processed genomic and clinical data to support precision medicine through data sharing and collaborative analysis. The initial dataset includes various data types from NCI TCGA and TARGET projects, and data production started in June 2015 using an OpenStack-based private cloud. The GDC has analyzed more than 50,000 raw sequencing data inputs and generated different data types using the latest human genome reference build GRCh38, which are available for download and exploratory analysis at GDC Data Portal and Legacy Archive.
NATURE COMMUNICATIONS
(2021)
Letter
Dermatology
Mindy D. Szeto, Steven M. Lada, Sameeha S. Husayn, Colby L. Presley, Michelle Militello, Robert P. Dellavalle
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Toshifumi Fujioka, Nobutaka Numoto, Hiroyuki Akama, Kola Shilpa, Michiko Oka, Prodip K. Roy, Yarkali Krishna, Nobutoshi Ito, David Baker, Masayuki Oda, Fujie Tanaka
Summary: The study found that the directionality of protein catalysts can be altered by replacing one amino acid. Additionally, protein catalysts from the same protein scaffold exhibit different efficiency in catalyzing aldol and retro-aldol reactions.
Article
Chemistry, Multidisciplinary
Rebecca Crawshaw, Amy E. Crossley, Linus Johannissen, Ashleigh J. Burke, Sam Hay, Colin Levy, David Baker, Sarah L. Lovelock, Anthony P. Green
Summary: The combination of computational design and directed evolution has shown to be effective in creating enzymes with new functions and catalytic mechanisms for challenging chemical transformations. Through evolutionary optimization of a primitive design, an efficient and enantioselective enzyme was developed for a specific reaction, demonstrating that intricate catalytic devices can be built to promote demanding multi-step processes not observed in nature.
Editorial Material
Biochemical Research Methods
Minkyung Baek, David Baker
Review
Multidisciplinary Sciences
Sarah L. Lovelock, Rebecca Crawshaw, Sophie Basler, Colin Levy, David Baker, Donald Hilvert, Anthony P. Green
Summary: Designing efficient enzymes has a profound impact on chemistry, biotechnology, and medicine. Recent advances in protein engineering and computational methods have made it possible to optimize protein structures and generate efficient enzymes through laboratory evolution. Emerging methods like deep learning hold promise for improving the accuracy of protein design models.
Article
Multidisciplinary Sciences
Shuai Zhang, Robbie Sadre, Benjamin A. Legg, Harley Pyles, Talita Perciano, E. Wes Bethel, David Baker, Oliver Rubel, James J. De Yoreo
Summary: This study directly observes and quantifies the rotational dynamics of protein nanorods on solid-water interfaces using high-speed atomic force microscopy and machine learning techniques. The findings reveal the characteristics of transitions between different angular states and provide insights into the self-assembly and other orientationally anisotropic outcomes of biomolecules at these interfaces.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Sicong Yao, Adam Moyer, Yiwu Zheng, Yang Shen, Xiaoting Meng, Chong Yuan, Yibing Zhao, Hongwei Yao, David Baker, Chuanliu Wu
Summary: Peptide heterodimers are functional macromolecules and molecular tools with wide applications in chemical and synthetic biology. In this study, the authors report the successful design, synthesis, and application of peptide heterodimers with mutual orthogonality through computational de novo designs and a directed disulfide pairing strategy. These heterodimers can be utilized as scaffolds for generating functional molecules, as well as chemical tools or building blocks for protein labeling and crosslinking hybrids.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Brian L. Trippe, Buwei Huang, Erika A. DeBenedictis, Brian Coventry, Nicholas Bhattacharya, Kevin K. Yang, David Baker, Lorin Crawford
Summary: Sort-seq assays are commonly used in biological engineering to profile groups of cells based on their fluorescence characteristics. However, current methods introduce systematic bias. This study demonstrates that unbiased estimates can be obtained by incorporating randomness into the sorting process. The findings are validated through simulations and experiments, and extensions for estimating group level variances and using multi-bin sorters are described.
Article
Biotechnology & Applied Microbiology
Dingchang Lin, Xiuyuan Li, Eric Moult, Pojeong Park, Benjamin Tang, Hao Shen, Jonathan B. B. Grimm, Natalie Falco, Bill Z. Z. Jia, David Baker, Luke D. D. Lavis, Adam E. E. Cohen
Summary: Recording the transcriptional histories of cells can provide a deeper understanding of their developmental trajectory and response to external stimuli. This study introduces an engineered protein fiber that incorporates fluorescent marks to create a ticker tape-like history. By utilizing a reporter gene and high-resolution imaging, the cellular histories can be accurately read and the absolute timing determined. The protein-based ticker tape design has the potential for massively parallel single-cell recordings of various physiological processes.
NATURE BIOTECHNOLOGY
(2023)
Article
Multidisciplinary Sciences
Thomas W. Linsky, Kyle Noble, Autumn R. Tobin, Rachel Crow, Lauren Carter, Jeffrey L. Urbauer, David Baker, Eva-Maria Strauch
Summary: This study presents a computational platform for designing various small protein folds and sampling shape diversity. Through experimental validation of approximately 30,000 de novo protein designs, about 6,200 stable proteins were identified. The study also revealed protein folding rules and provided training data for machine learning.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Shristi Pandey, Anna J. Moyer, Summer B. Thyme
Summary: The zebrafish telencephalon has different types of neuronal cells that regulate complex behaviors. This study analyzed single-cell transcriptomes of cells from different ages to identify the cell types and their development. The results showed that some neuronal subtypes emerge or expand in number later in development. This research provides important insights into the transcriptional signatures and development of zebrafish telencephalon.
Article
Multidisciplinary Sciences
Enrico Rennella, Danny D. Sahtoe, David Baker, Lewis E. Kay
Summary: With recent advancements in calculating protein structures from amino acid sequences using AI algorithms, the next important step is to understand how dynamics is encoded in the primary protein sequence to improve function prediction. This study emphasizes the significance of dynamics in modulating the function of a designed protein called C34, which binds β-strands. By investigating the structural dynamics of C34 using NMR spectroscopy, the researchers show that manipulating conformations can enhance functionality in protein design.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Amir Motmaen, Justas Dauparas, Minkyung Baek, Mohamad H. Abedi, David Baker, Philip Bradley
Summary: This study develops a model for predicting peptide-binding proteins and peptide-MHC interactions by adding a classifier on top of the AlphaFold network. The model shows strong generalization and excellent performance.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Sanaa Mansoor, Minkyung Baek, David Juergens, Joseph L. Watson, David Baker
Summary: The study evaluates the performance of the RFjoint model for mutation effect prediction and finds that it achieves comparable accuracy to other models without specific training. RFjoint demonstrates a broad understanding of protein sequence-structure landscapes, making it a useful tool for protein modeling.
Article
Biochemical Research Methods
Minkyung Baek, Ryan Mchugh, Ivan Anishchenko, Hanlun Jiang, David Baker, Frank DiMaio
Summary: Protein-nucleic acid complexes have been a challenge in structure prediction, and this study introduces RoseTTAFoldNA as a method to predict their structures with high accuracy and practical value.