Eric Nguyen, Michael Poli, Matthew G. Durrant, Brian Kang, Dhruva Katrekar, David B. Li, Liam J. Bartie, Armin W. Thomas, Samuel H. King, Garyk Brixi, Jeremy Sullivan, Madelena Y. Ng, Ashley Lewis, Aaron Lou, Stefano Ermon, Stephen A. Baccus, Tina Hernandez-Boussard, Christopher Ré, Patrick D. Hsu, Brian L. Hie
The genome is a sequence that encodes the DNA, RNA, and proteins that orchestrate an organism’s function. We present Evo, a long-context genomic foundation model with a frontier architecture trained on millions of prokaryotic and phage genomes, and report scaling laws on DNA to complement observations in language and vision. Evo generalizes across DNA, RNA, and proteins, enabling zero-shot function prediction competitive with domain-specific language models and the generation of functional CRISPR-Cas and transposon systems, representing the first examples of protein-RNA and protein-DNA codesign with a language model. Evo also learns how small mutations affect whole-organism fitness and generates megabase-scale sequences with plausible genomic architecture. These prediction and generation capabilities span molecular to genomic scales of complexity, advancing our understanding and control of biology.
基因组是编码 DNA、RNA 和蛋白质的序列，它们协调着生物体的功能。我们介绍的 Evo 是一种长语境基因组基础模型，其前沿架构是在数百万个原核生物和噬菌体基因组上训练出来的，并报告了 DNA 的缩放规律，以补充语言和视觉方面的观察结果。Evo 可在 DNA、RNA 和蛋白质之间进行泛化，实现了与特定领域语言模型竞争的零射频功能预测，并生成了功能性 CRISPR-Cas 和转座子系统，这是利用语言模型进行蛋白质-RNA 和蛋白质-DNA 编码设计的首个实例。Evo 还能了解微小突变如何影响整个生物体的适应性，并生成具有可信基因组结构的巨碱基序列。这些预测和生成能力跨越了从分子到基因组的复杂尺度，促进了我们对生物学的理解和控制。
{"title":"Sequence modeling and design from molecular to genome scale with Evo","authors":"Eric Nguyen, Michael Poli, Matthew G. Durrant, Brian Kang, Dhruva Katrekar, David B. Li, Liam J. Bartie, Armin W. Thomas, Samuel H. King, Garyk Brixi, Jeremy Sullivan, Madelena Y. Ng, Ashley Lewis, Aaron Lou, Stefano Ermon, Stephen A. Baccus, Tina Hernandez-Boussard, Christopher Ré, Patrick D. Hsu, Brian L. Hie","doi":"10.1126/science.ado9336","DOIUrl":"10.1126/science.ado9336","url":null,"abstract":"<div >The genome is a sequence that encodes the DNA, RNA, and proteins that orchestrate an organism’s function. We present Evo, a long-context genomic foundation model with a frontier architecture trained on millions of prokaryotic and phage genomes, and report scaling laws on DNA to complement observations in language and vision. Evo generalizes across DNA, RNA, and proteins, enabling zero-shot function prediction competitive with domain-specific language models and the generation of functional CRISPR-Cas and transposon systems, representing the first examples of protein-RNA and protein-DNA codesign with a language model. Evo also learns how small mutations affect whole-organism fitness and generates megabase-scale sequences with plausible genomic architecture. These prediction and generation capabilities span molecular to genomic scales of complexity, advancing our understanding and control of biology.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"386 6723","pages":""},"PeriodicalIF":44.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Advances in genomics, proteomics, and metabolomics have revealed associations between specific microbiota species in health and disease. However, the precise mechanism(s) of action for many microbiota species and molecules have not been fully elucidated, limiting the development of microbiota-based diagnostics and therapeutics. In this Review, we highlight innovative chemical and genetic approaches that are enabling the dissection of microbiota mechanisms and providing causation in health and disease. Although specific microbiota molecules and mechanisms have begun to emerge, new approaches are still needed to go beyond phenotypic associations and translate microbiota discoveries into actionable targets and therapeutic leads to prevent and treat diseases.
{"title":"Chemical genetic approaches to dissect microbiota mechanisms in health and disease","authors":"Xinglin Yang, Howard C. Hang","doi":"10.1126/science.ado8548","DOIUrl":"10.1126/science.ado8548","url":null,"abstract":"<div >Advances in genomics, proteomics, and metabolomics have revealed associations between specific microbiota species in health and disease. However, the precise mechanism(s) of action for many microbiota species and molecules have not been fully elucidated, limiting the development of microbiota-based diagnostics and therapeutics. In this Review, we highlight innovative chemical and genetic approaches that are enabling the dissection of microbiota mechanisms and providing causation in health and disease. Although specific microbiota molecules and mechanisms have begun to emerge, new approaches are still needed to go beyond phenotypic associations and translate microbiota discoveries into actionable targets and therapeutic leads to prevent and treat diseases.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"386 6723","pages":""},"PeriodicalIF":44.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zexian Cui, Qing Yang, Yan-Qiang Zhang, Chenyuan Wang, Haiyang Xian, Zhiming Chen, Zhiyong Xiao, Yuqi Qian, James W Head, Clive R Neal, Long Xiao, Fanglu Luo, Jinyou Chen, Pengli He, Yonghua Cao, Qin Zhou, Fangfang Huang, Linli Chen, Bo Wei, Jintuan Wang, Ya-Nan Yang, Shan Li, Yiping Yang, Xiaoju Lin, Jianxi Zhu, Le Zhang, Yi-Gang Xu
Remote sensing observations have shown that the far side of the Moon (lunar farside) has different geology and rock composition to the near side, including the abundances of potassium, rare earth elements, and phosphorus (collectively known as KREEP). The Chang'e-6 (CE-6) spacecraft collected samples from the South Pole-Aitken (SPA) basin on the farside and brought them to Earth. We use lead-lead and rubidium-strontium isotope systems to date low-titanium basalt in a CE-6 sample, finding a consistent age of 2830 ± 5 million years. We interpret this as the date of volcanism in SPA and incorporate it into lunar crater chronology. Strontium, neodymium and lead isotopes indicate the volcanic magma was from a lunar mantle source depleted in incompatible elements and containing almost no KREEP component.
{"title":"A sample of the Moon's far side retrieved by Chang'e-6 contains 2.83-billion-year-old basalt.","authors":"Zexian Cui, Qing Yang, Yan-Qiang Zhang, Chenyuan Wang, Haiyang Xian, Zhiming Chen, Zhiyong Xiao, Yuqi Qian, James W Head, Clive R Neal, Long Xiao, Fanglu Luo, Jinyou Chen, Pengli He, Yonghua Cao, Qin Zhou, Fangfang Huang, Linli Chen, Bo Wei, Jintuan Wang, Ya-Nan Yang, Shan Li, Yiping Yang, Xiaoju Lin, Jianxi Zhu, Le Zhang, Yi-Gang Xu","doi":"10.1126/science.adt1093","DOIUrl":"10.1126/science.adt1093","url":null,"abstract":"<p><p>Remote sensing observations have shown that the far side of the Moon (lunar farside) has different geology and rock composition to the near side, including the abundances of potassium, rare earth elements, and phosphorus (collectively known as KREEP). The Chang'e-6 (CE-6) spacecraft collected samples from the South Pole-Aitken (SPA) basin on the farside and brought them to Earth. We use lead-lead and rubidium-strontium isotope systems to date low-titanium basalt in a CE-6 sample, finding a consistent age of 2830 ± 5 million years. We interpret this as the date of volcanism in SPA and incorporate it into lunar crater chronology. Strontium, neodymium and lead isotopes indicate the volcanic magma was from a lunar mantle source depleted in incompatible elements and containing almost no KREEP component.</p>","PeriodicalId":21678,"journal":{"name":"Science","volume":" ","pages":"eadt1093"},"PeriodicalIF":44.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142627358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"How to build a human: Piecing together the body’s cellular puzzle","authors":"Jarrod Shilts","doi":"10.1126/science.adt9012","DOIUrl":"10.1126/science.adt9012","url":null,"abstract":"","PeriodicalId":21678,"journal":{"name":"Science","volume":"386 6723","pages":""},"PeriodicalIF":44.7,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/science.adt9012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142627498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. Muir, S. Lin, I. K. Aarrestad, H. R. Daniels, J. Ma, L. Tian, D. E. Olson, C. K. Kim
Psychedelics hold promise as alternate treatments for neuropsychiatric disorders. However, the neural mechanisms by which they drive adaptive behavioral effects remain unclear. We isolated the specific neurons modulated by a psychedelic to determine their role in driving behavior. Using a light- and calcium-dependent activity integrator, we genetically tagged psychedelic-responsive neurons in the medial prefrontal cortex (mPFC) of mice. Single-nucleus RNA sequencing revealed that the psychedelic drove network-level activation of multiple cell types beyond just those expressing 5-hydroxytryptamine 2A receptors. We labeled psychedelic-responsive mPFC neurons with an excitatory channelrhodopsin to enable their targeted manipulation. We found that reactivation of these cells recapitulated the anxiolytic effects of the psychedelic without driving its hallucinogenic-like effects. These findings reveal essential insight into the cell-type–specific mechanisms underlying psychedelic-induced behavioral states.
{"title":"Isolation of psychedelic-responsive neurons underlying anxiolytic behavioral states","authors":"J. Muir, S. Lin, I. K. Aarrestad, H. R. Daniels, J. Ma, L. Tian, D. E. Olson, C. K. Kim","doi":"10.1126/science.adl0666","DOIUrl":"10.1126/science.adl0666","url":null,"abstract":"<div >Psychedelics hold promise as alternate treatments for neuropsychiatric disorders. However, the neural mechanisms by which they drive adaptive behavioral effects remain unclear. We isolated the specific neurons modulated by a psychedelic to determine their role in driving behavior. Using a light- and calcium-dependent activity integrator, we genetically tagged psychedelic-responsive neurons in the medial prefrontal cortex (mPFC) of mice. Single-nucleus RNA sequencing revealed that the psychedelic drove network-level activation of multiple cell types beyond just those expressing 5-hydroxytryptamine 2A receptors. We labeled psychedelic-responsive mPFC neurons with an excitatory channelrhodopsin to enable their targeted manipulation. We found that reactivation of these cells recapitulated the anxiolytic effects of the psychedelic without driving its hallucinogenic-like effects. These findings reveal essential insight into the cell-type–specific mechanisms underlying psychedelic-induced behavioral states.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"386 6723","pages":""},"PeriodicalIF":44.7,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bianca Lopez, Keith T. Smith, Brent Grocholski, Mattia Maroso, Jake S. Yeston, Jesse Smith, Stella M. Hurtley, Courtney Malo, Michael A. Funk, Di Jiang, L. Bryan Ray, Ankit Walia, Phil Szuromi, Ian S. Osborne, Hannah M. Isles, Leslie K. Ferrarelli
{"title":"In Science Journals","authors":"Bianca Lopez, Keith T. Smith, Brent Grocholski, Mattia Maroso, Jake S. Yeston, Jesse Smith, Stella M. Hurtley, Courtney Malo, Michael A. Funk, Di Jiang, L. Bryan Ray, Ankit Walia, Phil Szuromi, Ian S. Osborne, Hannah M. Isles, Leslie K. Ferrarelli","doi":"10.1126/science.adu5505","DOIUrl":"10.1126/science.adu5505","url":null,"abstract":"","PeriodicalId":21678,"journal":{"name":"Science","volume":"386 6723","pages":""},"PeriodicalIF":44.7,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/science.adu5505","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142627541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rachel C. Rohde, Kurtis M. Carsch, Matthew N. Dods, Henry Z. H. Jiang, Alexandra R. McIsaac, Ryan A. Klein, Hyunchul Kwon, Sarah L. Karstens, Yang Wang, Adrian J. Huang, Jordan W. Taylor, Yuto Yabuuchi, Nikolay V. Tkachenko, Katie R. Meihaus, Hiroyasu Furukawa, Danielle R. Yahne, Kaitlyn E. Engler, Karen C. Bustillo, Andrew M. Minor, Jeffrey A. Reimer, Martin Head-Gordon, Craig M. Brown, Jeffrey R. Long
Carbon capture can mitigate point-source carbon dioxide (CO2) emissions, but hurdles remain that impede the widespread adoption of amine-based technologies. Capturing CO2 at temperatures closer to those of many industrial exhaust streams (>200°C) is of interest, although metal oxide absorbents that operate at these temperatures typically exhibit sluggish CO2 absorption kinetics and instability to cycling. Here, we report a porous metal–organic framework featuring terminal zinc hydride sites that reversibly bind CO2 at temperatures above 200°C—conditions that are unprecedented for intrinsically porous materials. Gas adsorption, structural, spectroscopic, and computational analyses elucidate the rapid, reversible nature of this transformation. Extended cycling and breakthrough analyses reveal that the material is capable of deep carbon capture at low CO2 concentrations and high temperatures relevant to postcombustion capture.
{"title":"High-temperature carbon dioxide capture in a porous material with terminal zinc hydride sites","authors":"Rachel C. Rohde, Kurtis M. Carsch, Matthew N. Dods, Henry Z. H. Jiang, Alexandra R. McIsaac, Ryan A. Klein, Hyunchul Kwon, Sarah L. Karstens, Yang Wang, Adrian J. Huang, Jordan W. Taylor, Yuto Yabuuchi, Nikolay V. Tkachenko, Katie R. Meihaus, Hiroyasu Furukawa, Danielle R. Yahne, Kaitlyn E. Engler, Karen C. Bustillo, Andrew M. Minor, Jeffrey A. Reimer, Martin Head-Gordon, Craig M. Brown, Jeffrey R. Long","doi":"10.1126/science.adk5697","DOIUrl":"10.1126/science.adk5697","url":null,"abstract":"<div >Carbon capture can mitigate point-source carbon dioxide (CO<sub>2</sub>) emissions, but hurdles remain that impede the widespread adoption of amine-based technologies. Capturing CO<sub>2</sub> at temperatures closer to those of many industrial exhaust streams (>200°C) is of interest, although metal oxide absorbents that operate at these temperatures typically exhibit sluggish CO<sub>2</sub> absorption kinetics and instability to cycling. Here, we report a porous metal–organic framework featuring terminal zinc hydride sites that reversibly bind CO<sub>2</sub> at temperatures above 200°C—conditions that are unprecedented for intrinsically porous materials. Gas adsorption, structural, spectroscopic, and computational analyses elucidate the rapid, reversible nature of this transformation. Extended cycling and breakthrough analyses reveal that the material is capable of deep carbon capture at low CO<sub>2</sub> concentrations and high temperatures relevant to postcombustion capture.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"386 6723","pages":""},"PeriodicalIF":44.7,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carbon capture and sequestration can help limit carbon dioxide (CO2) emissions and maintain the annual global temperature increase to below 1.5? to 2°C above preindustrial levels, a goal set by the 2015 Paris Agreement (1). Sorbents—porous materials that capture a specific liquid or gas—play a role in achieving this. However, the existing technology only adsorbs CO2 at low temperatures and is not suitable for removing CO2 from hot gas streams emitted by industrial plants. Given that industrial processes produce more than 50% of the total global CO2 emissions (2), it is critical to develop sorbents that separate carbon at high temperatures. On page 814 of this issue, Rohde et al. (3) report a metal-organic framework (MOF)–based solid sorbent that reversibly captures CO2 at low concentrations and at temperatures up to 300°C. This could potentially be scaled for use in industrial exhaust systems.
激活金属有机框架可在高温下捕获二氧化碳。
{"title":"Heat up to catch carbon","authors":"He Li, Dan Zhao","doi":"10.1126/science.adt4825","DOIUrl":"10.1126/science.adt4825","url":null,"abstract":"<div >Carbon capture and sequestration can help limit carbon dioxide (CO<sub>2</sub>) emissions and maintain the annual global temperature increase to below 1.5? to 2°C above preindustrial levels, a goal set by the 2015 Paris Agreement (<i>1</i>). Sorbents—porous materials that capture a specific liquid or gas—play a role in achieving this. However, the existing technology only adsorbs CO<sub>2</sub> at low temperatures and is not suitable for removing CO<sub>2</sub> from hot gas streams emitted by industrial plants. Given that industrial processes produce more than 50% of the total global CO<sub>2</sub> emissions (<i>2</i>), it is critical to develop sorbents that separate carbon at high temperatures. On page 814 of this issue, Rohde <i>et al</i>. (<i>3</i>) report a metal-organic framework (MOF)–based solid sorbent that reversibly captures CO<sub>2</sub> at low concentrations and at temperatures up to 300°C. This could potentially be scaled for use in industrial exhaust systems.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"386 6723","pages":""},"PeriodicalIF":44.7,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142627495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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