{"title":"Anatomy of the 23andMe fall and implications for consumer genomics","authors":"Yaniv Erlich, Dina Zielinski","doi":"10.1038/s41587-025-02683-z","DOIUrl":"https://doi.org/10.1038/s41587-025-02683-z","url":null,"abstract":"23andMe’s bankruptcy serves as a moment of reflection for the direct-to-consumer (DTC) genomics industry. We analyzed 23andMe financial data and business practices to reveal the factors behind the fall of the company, once valued at US $6 billion and now being considered for acquisition by Regeneron for merely $250 million. Key challenges faced by 23andMe in monetizing its genomic data reveal that this information, at least in a typical DTC setting, is simply not worth that much.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"1 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144165316","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}
{"title":"Self-supervised learning from small-molecule mass spectrometry data","authors":"Wout Bittremieux, William Stafford Noble","doi":"10.1038/s41587-025-02677-x","DOIUrl":"https://doi.org/10.1038/s41587-025-02677-x","url":null,"abstract":"A self-supervised approach to learning from 24 million spectra generates a foundation model for detecting and characterizing small molecules by tandem mass spectrometry.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"56 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122708","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}
Roman Bushuiev, Anton Bushuiev, Raman Samusevich, Corinna Brungs, Josef Sivic, Tomáš Pluskal
{"title":"Self-supervised learning of molecular representations from millions of tandem mass spectra using DreaMS","authors":"Roman Bushuiev, Anton Bushuiev, Raman Samusevich, Corinna Brungs, Josef Sivic, Tomáš Pluskal","doi":"10.1038/s41587-025-02663-3","DOIUrl":"https://doi.org/10.1038/s41587-025-02663-3","url":null,"abstract":"<p>Characterizing biological and environmental samples at a molecular level primarily uses tandem mass spectroscopy (MS/MS), yet the interpretation of tandem mass spectra from untargeted metabolomics experiments remains a challenge. Existing computational methods for predictions from mass spectra rely on limited spectral libraries and on hard-coded human expertise. Here we introduce a transformer-based neural network pre-trained in a self-supervised way on millions of unannotated tandem mass spectra from our GNPS Experimental Mass Spectra (GeMS) dataset mined from the MassIVE GNPS repository. We show that pre-training our model to predict masked spectral peaks and chromatographic retention orders leads to the emergence of rich representations of molecular structures, which we named Deep Representations Empowering the Annotation of Mass Spectra (DreaMS). Further fine-tuning the neural network yields state-of-the-art performance across a variety of tasks. We make our new dataset and model available to the community and release the DreaMS Atlas—a molecular network of 201 million MS/MS spectra constructed using DreaMS annotations.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"56 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122573","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}
Wei Zheng, Qiqige Wuyun, Yang Li, Quancheng Liu, Xiaogen Zhou, Chunxiang Peng, Yiheng Zhu, Lydia Freddolino, Yang Zhang
{"title":"Deep-learning-based single-domain and multidomain protein structure prediction with D-I-TASSER","authors":"Wei Zheng, Qiqige Wuyun, Yang Li, Quancheng Liu, Xiaogen Zhou, Chunxiang Peng, Yiheng Zhu, Lydia Freddolino, Yang Zhang","doi":"10.1038/s41587-025-02654-4","DOIUrl":"https://doi.org/10.1038/s41587-025-02654-4","url":null,"abstract":"<p>The dominant success of deep learning techniques on protein structure prediction has challenged the necessity and usefulness of traditional force field-based folding simulations. We proposed a hybrid approach, deep-learning-based iterative threading assembly refinement (D-I-TASSER), which constructs atomic-level protein structural models by integrating multisource deep learning potentials with iterative threading fragment assembly simulations. D-I-TASSER introduces a domain splitting and assembly protocol for the automated modeling of large multidomain protein structures. Benchmark tests and the most recent critical assessment of protein structure prediction, 15 experiments demonstrate that D-I-TASSER outperforms AlphaFold2 and AlphaFold3 on both single-domain and multidomain proteins. Large-scale folding experiments further show that D-I-TASSER could fold 81% of protein domains and 73% of full-chain sequences in the human proteome with results highly complementary to recently released models by AlphaFold2. These results highlight a new avenue to integrate deep learning with classical physics-based folding simulations for high-accuracy protein structure and function predictions that are usable in genome-wide applications.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"1 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122574","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}
Soh Ishiguro, Kana Ishida, Rina C. Sakata, Minori Ichiraku, Ren Takimoto, Rina Yogo, Yusuke Kijima, Hideto Mori, Mamoru Tanaka, Samuel King, Shoko Tarumoto, Taro Tsujimura, Omar Bashth, Nanami Masuyama, Arman Adel, Hiromi Toyoshima, Motoaki Seki, Ju Hee Oh, Anne-Sophie Archambault, Keiji Nishida, Akihiko Kondo, Satoru Kuhara, Hiroyuki Aburatani, Ramon I. Klein Geltink, Takuya Yamamoto, Nika Shakiba, Yasuhiro Takashima, Nozomu Yachie
{"title":"A multi-kingdom genetic barcoding system for precise clone isolation","authors":"Soh Ishiguro, Kana Ishida, Rina C. Sakata, Minori Ichiraku, Ren Takimoto, Rina Yogo, Yusuke Kijima, Hideto Mori, Mamoru Tanaka, Samuel King, Shoko Tarumoto, Taro Tsujimura, Omar Bashth, Nanami Masuyama, Arman Adel, Hiromi Toyoshima, Motoaki Seki, Ju Hee Oh, Anne-Sophie Archambault, Keiji Nishida, Akihiko Kondo, Satoru Kuhara, Hiroyuki Aburatani, Ramon I. Klein Geltink, Takuya Yamamoto, Nika Shakiba, Yasuhiro Takashima, Nozomu Yachie","doi":"10.1038/s41587-025-02649-1","DOIUrl":"https://doi.org/10.1038/s41587-025-02649-1","url":null,"abstract":"<p>Cell-tagging strategies with DNA barcodes have enabled the analysis of clone size dynamics and clone-restricted transcriptomic landscapes in heterogeneous populations. However, isolating a target clone that displays a specific phenotype from a complex population remains challenging. Here we present a multi-kingdom genetic barcoding system, CloneSelect, which enables a target cell clone to be triggered to express a reporter gene for isolation through barcode-specific CRISPR base editing. In CloneSelect, cells are first stably tagged with DNA barcodes and propagated so that their subpopulation can be subjected to a given experiment. A clone that shows a phenotype or genotype of interest at a given time can then be isolated from the initial or subsequent cell pools stored during the experiment using CRISPR base editing. CloneSelect is scalable and compatible with single-cell RNA sequencing. We demonstrate the versatility of CloneSelect in human embryonic kidney 293T cells, mouse embryonic stem cells, human pluripotent stem cells, yeast cells and bacterial cells.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"45 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103958","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}
{"title":"Beyond cell atlases: spatial biology reveals mechanisms behind disease","authors":"","doi":"10.1038/s41587-025-02699-5","DOIUrl":"https://doi.org/10.1038/s41587-025-02699-5","url":null,"abstract":"As the next generation of spatial transcriptomics tools hits the market, researchers are uncovering previously unknown interactions that could transform clinical research.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"11 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103957","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}
{"title":"Retargeted retrotransposons insert multi-kilobase cargo at new sites","authors":"Iris Marchal","doi":"10.1038/s41587-025-02682-0","DOIUrl":"https://doi.org/10.1038/s41587-025-02682-0","url":null,"abstract":"<p>Site-specific retroelements, such as R2 retrotransposons, have potential as programmable genome-editing systems, but so far have only been used for targeted insertion at genomic safe-harbor loci. In a paper now published in <i>Nature</i>, Fell et al. profile the evolution of site-specific retrotransposon families to gain insight into target site preferences, which they then used to engineer reprogramming.</p><p>By surveying 4,464 animal assemblies derived from Genbank, the authors discovered several new site-specific retrotransposon families, including families with multiple integration preferences and with differing 5′ and 3′ site predictions, which might indicate retargeting mechanisms. They zoned in on a retrotransposon from the zebra finch (<i>Taeniopygia guttata</i>), called R2<i>Tg</i>, for biochemical profiling and characterized its activity in mammalian cells, which showed that R2<i>Tg</i> can insert payloads by reverse transcription of RNA and nicking of genomic DNA. Notably, the authors found that R2<i>Tg</i> can be retargeted by engineering the payload, which allowed scarless insertion of the payload at new genomic sites. The activity of the reprogrammed R2<i>Tg</i> was enhanced by fusing it with CRISPR–Cas9 nickase.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"16 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144066955","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}
{"title":"Fruit waste for catwalk fashion","authors":"","doi":"10.1038/s41587-025-02679-9","DOIUrl":"https://doi.org/10.1038/s41587-025-02679-9","url":null,"abstract":"<p>Polybion creates this next-generation material by feeding a mango fruit waste slurry to <i>Acetobacter</i> bacteria genetically modified to speed up their metabolism. The bacteria feed on the sugar and turn it into cellulose to form a gel-like mat on the surface of the fermentation tank. Bacteria employ this strategy to survive in harsh environments. “It’s a shelter they create [against] the radiation of the sun or to inhibit the growth of other competitors,” says José Manuel Aguilar-Yáñez, CSO of Polybion.</p><p>Once the skin-like layer, or pellicle, grows to the required thickness, Polybion scoops up the creamy-colored biofabric and washes it to kill the bacteria, then dries it in their solar-powered factory for up to 24 hours, after which the material undergoes tanning and dyeing in a process similar to that used for leather. Since its creation in 2020, the Polybion team has created one million square feet of Celium.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"37 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144066956","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}
{"title":"FDA pushes to replace animal testing","authors":"","doi":"10.1038/s41587-025-02690-0","DOIUrl":"https://doi.org/10.1038/s41587-025-02690-0","url":null,"abstract":"<p>The US Food and Drug Administration plans to introduce computational modeling and other innovative methods to replace animal testing in preclinical drug safety studies, according to a roadmap released in April. By encouraging drug sponsors to embrace organ-on-a chip, in silico modeling, organoid and other in vitro assays, the FDA aims to reduce animal testing to the extent that it becomes “the exception rather than the norm” within 3–5 years. The FDA’s roadmap builds on the 2022 FDA Modernization Act 2.0, passed by Congress, which removed the requirement for animal testing in biosimilar biologics’ applications.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"218 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144066965","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}
{"title":"Biotech news from around the world","authors":"","doi":"10.1038/s41587-025-02680-2","DOIUrl":"https://doi.org/10.1038/s41587-025-02680-2","url":null,"abstract":"<p>As part of its Dare2eraD TB initiative to combat the challenge of drug-resistant tuberculosis, Indian researchers sequence the genomes of 10,000 <i>Mycobacterium tuberculosis</i> isolates. Sequencing will aid in personalizing antibiotic prescription, allowing faster, more effective treatment. India has set the goal of eliminating TB by 2025, five years ahead of the World Health Organization’s global target.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"6 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144066964","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}