Nature MethodsPub Date : 2024-11-22DOI: 10.1038/s41592-024-02513-1
Minxing Pang, Tarun Kanti Roy, Xiaodong Wu, Kai Tan
{"title":"CelloType: a unified model for segmentation and classification of tissue images.","authors":"Minxing Pang, Tarun Kanti Roy, Xiaodong Wu, Kai Tan","doi":"10.1038/s41592-024-02513-1","DOIUrl":"10.1038/s41592-024-02513-1","url":null,"abstract":"<p><p>Cell segmentation and classification are critical tasks in spatial omics data analysis. Here we introduce CelloType, an end-to-end model designed for cell segmentation and classification for image-based spatial omics data. Unlike the traditional two-stage approach of segmentation followed by classification, CelloType adopts a multitask learning strategy that integrates these tasks, simultaneously enhancing the performance of both. CelloType leverages transformer-based deep learning techniques for improved accuracy in object detection, segmentation and classification. It outperforms existing segmentation methods on a variety of multiplexed fluorescence and spatial transcriptomic images. In terms of cell type classification, CelloType surpasses a model composed of state-of-the-art methods for individual tasks and a high-performance instance segmentation model. Using multiplexed tissue images, we further demonstrate the utility of CelloType for multiscale segmentation and classification of both cellular and noncellular elements in a tissue. The enhanced accuracy and multitask learning ability of CelloType facilitate automated annotation of rapidly growing spatial omics data.</p>","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":" ","pages":""},"PeriodicalIF":36.1,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nature MethodsPub Date : 2024-11-21DOI: 10.1038/s41592-024-02487-0
Tao Shen, Zhihang Hu, Siqi Sun, Di Liu, Felix Wong, Jiuming Wang, Jiayang Chen, Yixuan Wang, Liang Hong, Jin Xiao, Liangzhen Zheng, Tejas Krishnamoorthi, Irwin King, Sheng Wang, Peng Yin, James J. Collins, Yu Li
{"title":"Accurate RNA 3D structure prediction using a language model-based deep learning approach","authors":"Tao Shen, Zhihang Hu, Siqi Sun, Di Liu, Felix Wong, Jiuming Wang, Jiayang Chen, Yixuan Wang, Liang Hong, Jin Xiao, Liangzhen Zheng, Tejas Krishnamoorthi, Irwin King, Sheng Wang, Peng Yin, James J. Collins, Yu Li","doi":"10.1038/s41592-024-02487-0","DOIUrl":"10.1038/s41592-024-02487-0","url":null,"abstract":"Accurate prediction of RNA three-dimensional (3D) structures remains an unsolved challenge. Determining RNA 3D structures is crucial for understanding their functions and informing RNA-targeting drug development and synthetic biology design. The structural flexibility of RNA, which leads to the scarcity of experimentally determined data, complicates computational prediction efforts. Here we present RhoFold+, an RNA language model-based deep learning method that accurately predicts 3D structures of single-chain RNAs from sequences. By integrating an RNA language model pretrained on ~23.7 million RNA sequences and leveraging techniques to address data scarcity, RhoFold+ offers a fully automated end-to-end pipeline for RNA 3D structure prediction. Retrospective evaluations on RNA-Puzzles and CASP15 natural RNA targets demonstrate the superiority of RhoFold+ over existing methods, including human expert groups. Its efficacy and generalizability are further validated through cross-family and cross-type assessments, as well as time-censored benchmarks. Additionally, RhoFold+ predicts RNA secondary structures and interhelical angles, providing empirically verifiable features that broaden its applicability to RNA structure and function studies. RhoFold+ is an end-to-end language model-based deep learning method to predict RNA three-dimensional structures of single-chain RNAs from sequences.","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"21 12","pages":"2287-2298"},"PeriodicalIF":36.1,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41592-024-02487-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nature MethodsPub Date : 2024-11-21DOI: 10.1038/s41592-024-02488-z
{"title":"Large language modeling and deep learning shed light on RNA structure prediction","authors":"","doi":"10.1038/s41592-024-02488-z","DOIUrl":"10.1038/s41592-024-02488-z","url":null,"abstract":"We present an RNA language model-based deep learning pipeline for accurate and rapid de novo RNA 3D structure prediction, demonstrating strong accuracy in modeling single-stranded RNAs and excellent generalization across RNA families and types while also being capable of capturing local features such as interhelical angles and secondary structures.","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"21 12","pages":"2237-2238"},"PeriodicalIF":36.1,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nature MethodsPub Date : 2024-11-19DOI: 10.1038/s41592-024-02527-9
Vivien Marx
{"title":"First-timers at a huge meeting","authors":"Vivien Marx","doi":"10.1038/s41592-024-02527-9","DOIUrl":"10.1038/s41592-024-02527-9","url":null,"abstract":"At some meetings, one gets to know all attendees. But at large conferences, that’s rather impossible. Some first-time attendees share how they navigated the sizable Society for Neuroscience annual meeting.","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"21 12","pages":"2197-2197"},"PeriodicalIF":36.1,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nature MethodsPub Date : 2024-11-19DOI: 10.1038/s41592-024-02502-4
Ann Cirincione, Danny Simpson, Weihao Yan, Ryan McNulty, Purnima Ravisankar, Sabrina C Solley, Jun Yan, Fabian Lim, Emma K Farley, Mona Singh, Britt Adamson
{"title":"A benchmarked, high-efficiency prime editing platform for multiplexed dropout screening.","authors":"Ann Cirincione, Danny Simpson, Weihao Yan, Ryan McNulty, Purnima Ravisankar, Sabrina C Solley, Jun Yan, Fabian Lim, Emma K Farley, Mona Singh, Britt Adamson","doi":"10.1038/s41592-024-02502-4","DOIUrl":"10.1038/s41592-024-02502-4","url":null,"abstract":"<p><p>Prime editing installs precise edits into the genome with minimal unwanted byproducts, but low and variable editing efficiencies have complicated application of the approach to high-throughput functional genomics. Here we assembled a prime editing platform capable of high-efficiency substitution editing suitable for functional interrogation of small genetic variants. We benchmarked this platform for pooled, loss-of-function screening using a library of ~240,000 engineered prime editing guide RNAs (epegRNAs) targeting ~17,000 codons with 1-3 bp substitutions. Comparing the abundance of these epegRNAs across screen samples identified negative selection phenotypes for 7,996 nonsense mutations targeted to 1,149 essential genes and for synonymous mutations that disrupted splice site motifs at 3' exon boundaries. Rigorous evaluation of codon-matched controls demonstrated that these phenotypes were highly specific to the intended edit. Altogether, we established a prime editing approach for multiplexed, functional characterization of genetic variants with simple readouts.</p>","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":" ","pages":""},"PeriodicalIF":36.1,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nature MethodsPub Date : 2024-11-19DOI: 10.1038/s41592-024-02522-0
Jonathan F Roth, Francisco J Sánchez-Rivera
{"title":"Precision mutational scanning: your multipass to the future of genetics.","authors":"Jonathan F Roth, Francisco J Sánchez-Rivera","doi":"10.1038/s41592-024-02522-0","DOIUrl":"https://doi.org/10.1038/s41592-024-02522-0","url":null,"abstract":"","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":" ","pages":""},"PeriodicalIF":36.1,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nature MethodsPub Date : 2024-11-19DOI: 10.1038/s41592-024-02501-5
Denis Cipurko, Tatsuki Ueda, Linghan Mei, Nicolas Chevrier
{"title":"Repurposing large-format microarrays for scalable spatial transcriptomics.","authors":"Denis Cipurko, Tatsuki Ueda, Linghan Mei, Nicolas Chevrier","doi":"10.1038/s41592-024-02501-5","DOIUrl":"https://doi.org/10.1038/s41592-024-02501-5","url":null,"abstract":"<p><p>Spatiomolecular analyses are key to study tissue functions and malfunctions. However, we lack profiling tools for spatial transcriptomics that are easy to adopt, low cost and scalable in terms of sample size and number. Here, we describe a method, Array-seq, to repurpose classical oligonucleotide microarrays for spatial transcriptomics profiling. We generate Array-seq slides from microarrays carrying custom-design probes that contain common sequences flanking unique barcodes at known coordinates. Then we perform a simple, two-step reaction that produces mRNA capture probes across all spots on the microarray. We demonstrate that Array-seq yields spatial transcriptomes with high detection sensitivity and localization specificity using histological sections from mouse tissues as test systems. Moreover, we show that the large surface area of Array-seq slides yields spatial transcriptomes (i) at high throughput by profiling multi-organ sections, (ii) in three dimensions by processing serial sections from one sample, and (iii) across whole human organs. Thus, by combining classical DNA microarrays and next-generation sequencing, we have created a simple and flexible platform for spatiomolecular studies of small-to-large specimens at scale.</p>","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":" ","pages":""},"PeriodicalIF":36.1,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nature MethodsPub Date : 2024-11-18DOI: 10.1038/s41592-024-02505-1
Yun-Tao Liu, Hongcheng Fan, Jason J Hu, Z Hong Zhou
{"title":"Overcoming the preferred-orientation problem in cryo-EM with self-supervised deep learning.","authors":"Yun-Tao Liu, Hongcheng Fan, Jason J Hu, Z Hong Zhou","doi":"10.1038/s41592-024-02505-1","DOIUrl":"10.1038/s41592-024-02505-1","url":null,"abstract":"<p><p>While advances in single-particle cryo-EM have enabled the structural determination of macromolecular complexes at atomic resolution, particle orientation bias (the 'preferred' orientation problem) remains a complication for most specimens. Existing solutions have relied on biochemical and physical strategies applied to the specimen and are often complex and challenging. Here, we develop spIsoNet, an end-to-end self-supervised deep learning-based software to address map anisotropy and particle misalignment caused by the preferred-orientation problem. Using preferred-orientation views to recover molecular information in under-sampled views, spIsoNet improves both angular isotropy and particle alignment accuracy during 3D reconstruction. We demonstrate spIsoNet's ability to generate near-isotropic reconstructions from representative biological systems with limited views, including ribosomes, β-galactosidases and a previously intractable hemagglutinin trimer dataset. spIsoNet can also be generalized to improve map isotropy and particle alignment of preferentially oriented molecules in subtomogram averaging. Therefore, without additional specimen-preparation procedures, spIsoNet provides a general computational solution to the preferred-orientation problem.</p>","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":" ","pages":""},"PeriodicalIF":36.1,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nature MethodsPub Date : 2024-11-18DOI: 10.1038/s41592-024-02520-2
Romain F. Laine
{"title":"Content-aware motion correction for multi-shot imaging","authors":"Romain F. Laine","doi":"10.1038/s41592-024-02520-2","DOIUrl":"10.1038/s41592-024-02520-2","url":null,"abstract":"A new deep learning approach enables motion correction across sequential acquisitions, even if each image in the sequence was acquired differently.","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"21 12","pages":"2235-2236"},"PeriodicalIF":36.1,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}