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AI-enhanced protein design makes proteins that have never existed
Michael EisensteinÂÂ
Rapid-response manufacturing of adenovirus-vectored vaccines
Carina C. D. Joe, Nitin Chopra, Piergiuseppe Nestola, Julia Niemann & Alexander D. DouglasÂ
Distinguishing and predicting drug patents
Colleen V. Chien, Nicholas Halkowski & Jeffrey KuhnÂ
Plant-inspired design of self-burying seed carrier
Jared B. FudgeÂÂ
Metatranscriptomes reveal increased diversity of viroid-like circular RNAs
Jared B. FudgeÂ
Mapping mRNA modifications for functional studies
Joshua D. Jones, Daniel E. Eyler & Kristin S. KoutmouÂ
Combining a deep neural network with physical properties for super-resolution live imaging
Mathematical modeling of epigenetic gene regulation during cell differentiation
Modeling intercellular communication in tissues using spatial graphs of cells
David S. Fischer, Anna C. Schaar & Fabian J. TheisÂ
doi : 10.1038/s41587-022-01467-z
Models of intercellular communication in tissues are based on molecular profiles of dissociated cells, are limited to receptor–ligand signaling and ignore spatial proximity in situ.
Engineered CRISPR prime editors with compact, untethered reverse transcriptases
Julian Grünewald, Bret R. Miller, Regan N. Szalay, Peter K. Cabeceiras, Christopher J. Woodilla, Eliza Jane B. Holtz, Karl Petri & J. Keith JoungÂ
doi : 10.1038/s41587-022-01473-1
The CRISPR prime editor PE2 consists of a Streptococcus pyogenes Cas9 nickase (nSpCas9) fused at its C-terminus to a Moloney murine leukemia virus reverse transcriptase (MMLV-RT). Here we show that separated nSpCas9 and MMLV-RT proteins function as efficiently as intact PE2 in human cells.
Quantitative sequencing using BID-seq uncovers abundant pseudouridines in mammalian mRNA at base resolution
Qing Dai, Li-Sheng Zhang, Hui-Lung Sun, Kinga Pajdzik, Lei Yang, Chang Ye, Cheng-Wei Ju, Shun Liu, Yuru Wang, Zhong Zheng, Linda Zhang, Bryan T. Harada, Xiaoyang Dou, Iryna Irkliyenko, Xinran Feng, Wen Zhang, Tao Pan & Chuan HeÂ
doi : 10.1038/s41587-022-01505-w
Functional characterization of pseudouridine (Ψ) in mammalian mRNA has been hampered by the lack of a quantitative method that maps Ψ in the whole transcriptome.
Absolute quantification of single-base m6A methylation in the mammalian transcriptome using GLORI
Cong Liu, Hanxiao Sun, Yunpeng Yi, Weiguo Shen, Kai Li, Ye Xiao, Fei Li, Yuchen Li, Yongkang Hou, Bo Lu, Wenqing Liu, Haowei Meng, Jinying Peng, Chengqi Yi & Jing WangÂ
doi : 10.1038/s41587-022-01487-9
N6-methyladenosine (m6A) is the most abundant RNA modification in mammalian cells and the best-studied epitranscriptomic mark. Despite the development of various tools to map m6A, a transcriptome-wide method that enables absolute quantification of m6A at single-base resolution is lacking.
Rationalized deep learning super-resolution microscopy for sustained live imaging of rapid subcellular processes
Chang Qiao, Di Li, Yong Liu, Siwei Zhang, Kan Liu, Chong Liu, Yuting Guo, Tao Jiang, Chuyu Fang, Nan Li, Yunmin Zeng, Kangmin He, Xueliang Zhu, Jennifer Lippincott-Schwartz, Qionghai Dai & Dong LiÂ
doi : 10.1038/s41587-022-01471-3
The goal when imaging bioprocesses with optical microscopy is to acquire the most spatiotemporal information with the least invasiveness. Deep neural networks have substantially improved optical microscopy, including image super-resolution and restoration, but still have substantial potential for artifacts.
Precision mitochondrial DNA editing with high-fidelity DddA-derived base editors
Seonghyun Lee, Hyunji Lee, Gayoung Baek & Jin-Soo KimÂ
doi : 10.1038/s41587-022-01486-w
Bacterial toxin DddA-derived cytosine base editors (DdCBEs)�composed of split DddAtox (a cytosine deaminase specific to double-stranded DNA), custom-designed TALE (transcription activator-like effector) DNA-binding proteins, and a uracil glycosylase inhibitor�enable mitochondrial DNA (mtDNA) editing in human cells, which may pave the way for therapeutic correction of pathogenic mtDNA mutations in patients.
Multi-omic single-cell velocity models epigenome–transcriptome interactions and improves cell fate prediction
Chen Li, Maria C. Virgilio, Kathleen L. Collins & Joshua D. WelchÂ
doi : 10.1038/s41587-022-01476-y
Multi-omic single-cell datasets, in which multiple molecular modalities are profiled within the same cell, offer an opportunity to understand the temporal relationship between epigenome and transcriptome. To realize this potential, we developed MultiVelo, a differential equation model of gene expression that extends the RNA velocity framework to incorporate epigenomic data.
Discovery of drug–omics associations in type 2 diabetes with generative deep-learning models
Rosa Lundbye Allesøe, Agnete Troen Lundgaard, Ricardo Hernández Medina, Alejandro Aguayo-Orozco, Joachim Johansen, Jakob Nybo Nissen, Caroline Brorsson, Gianluca Mazzoni, Lili Niu, Jorge Hernansanz Biel, Valentas Brasas, Henry Webel, Michael Eriksen Benros, Anders Gorm Pedersen, Piotr Jaroslaw Chmura, Ulrik Plesner Jacobsen, Andrea Mari, Robert Koivula, Anubha Mahajan, Ana Vinuela, Juan Fernandez Tajes, Sapna Sharma, Mark Haid, Mun-Gwan Hong, IMI DIRECT Consortium
doi : 10.1038/s41587-022-01520-x
The application of multiple omics technologies in biomedical cohorts has the potential to reveal patient-level disease characteristics and individualized response to treatment. However, the scale and heterogeneous nature of multi-modal data makes integration and inference a non-trivial task.
Precise DNA cleavage using CRISPR-SpRYgests
Kathleen A. Christie, Jimmy A. Guo, Rachel A. Silverstein, Roman M. Doll, Megumu Mabuchi, Hannah E. Stutzman, Jiecong Lin, Linyuan Ma, Russell T. Walton, Luca Pinello, G. Brett Robb & Benjamin P. KleinstiverÂ
doi : 10.1038/s41587-022-01492-y
Methods for in vitro DNA cleavage and molecular cloning remain unable to precisely cleave DNA directly adjacent to bases of interest. Restriction enzymes (REs) must bind specific motifs, whereas wild-type CRISPR–Cas9 or CRISPR–Cas12 nucleases require protospacer adjacent motifs (PAMs).
Haplotype-aware analysis of somatic copy number variations from single-cell transcriptomes
Teng Gao, Ruslan Soldatov, Hirak Sarkar, Adam Kurkiewicz, Evan Biederstedt, Po-Ru Loh & Peter V. KharchenkoÂ
doi : 10.1038/s41587-022-01468-y
Genome instability and aberrant alterations of transcriptional programs both play important roles in cancer. Single-cell RNA sequencing (scRNA-seq) has the potential to investigate both genetic and nongenetic sources of tumor heterogeneity in a single assay.
Longitudinal data support university-based biomedical entrepreneurship education programs
Gabriel Vizgan, Zachary Hill-Whilton, Joy Achuonjei, Tucker Schweickart, Sadhana Chitale, Colleen Gillespie & Gabrielle Gold-von SimsonÂ
