洞察前沿，连接科研新知

完整作者

Daniel J Baker、Leon M Frommer、Ugur Uslu、Kisha K Patel、Daniel Zhu、Nils W Engel、James M George、Wencao Zhao、Samuel I Kim、Lisa Sun、Christopher Roselle、Philipp C Rommel、Regina M Young、Jonathan A Epstein、Sikander Hayat、Zoltan Arany、Carl H June

作者机构

• Center for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Cardiovascular Institute, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: bakerdj@upenn.edu.
• Department of Medicine 2, RWTH Aachen University, Medical Faculty, Aachen, Germany.
• Center for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, 97080 Würzburg, Germany.
• Center for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
• Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
• Cardiovascular Institute, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
• Cardiovascular Institute, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Institute for Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Department of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
• Department of Medicine 2, RWTH Aachen University, Medical Faculty, Aachen, Germany; Cardiovascular Research Institute, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Windreich Department of Artificial Intelligence and Human Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: shayat@ukaachen.de.
• Cardiovascular Institute, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: zarany@upenn.edu.
• Center for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Parker Institute for Cancer Immunotherapy at University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: cjune@upenn.edu.

技术路线

单细胞RNA测序数据（人类皮肤癌与健康组织）整合→AI驱动候选靶点筛选，结合公共数据集优化肿瘤组成、组织特异性与临床可行性→大语言模型优先排序与提名→GPNMB跨血液与实体瘤表达验证→构建人源GPNMB CAR T细胞→单核细胞白血病、黑色素瘤和结直肠腺癌小鼠模型抗肿瘤活性验证

最近 5 个完整年度引用趋势

完整作者

Zahir Ali、Haroon Butt、Raghad Alghamdi、Jose Luis Moreno Ramirez、Magdy Mahfouz

作者机构

• Laboratory for Genome Engineering and Synthetic Biology, Division of Biomedical Sciences, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia.
• Laboratory for Genome Engineering and Synthetic Biology, Division of Biomedical Sciences, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia. magdy.mahfouz@kaust.edu.sa.

技术路线

样本：本氏烟草与水稻愈伤组织；分析：基于TMV游离型报告系统重建R2活性，检测28S rDNA阵列定点整合效率与保真度，并统计水稻rDNA抗性盒整合效率

最近 5 个完整年度引用趋势

完整作者

Javier M Hernández-Sancho、Daniel C Volke、Pablo I Nikel

作者机构

• BRIGHT, Technical University of Denmark, 2800 Kongens Lyngby, Denmark.

技术路线

数据/样本：以Pseudomonas putida为宿主，构建基于Bxb1丝氨酸整合酶的级联双稳态开关，由鼠李糖诱导模块驱动，连接绝缘倒位模块产生二元OFF/ON转录状态；开关控制正交T7 RNA聚合酶基因以激活可替换的PT7靶模块；对整合酶与T7 RNA聚合酶基因进行翻译水平调谐。分析：评估开关效率、OFF态紧密性、诱导强度及去除诱导剂后的表型稳定性（遗传记忆）。验证：通过调控超活跃二鸟苷酸环化酶触发生物膜形成，并在2-氟顺,顺-黏康酸生产菌株中实现连续模式下开关介导的催化生物膜稳定产化。

最近 5 个完整年度引用趋势

完整作者

Xiaotong Wang、Jianping Xu、Yipeng Wang、Qingsheng Qi、Zhiguo Wang、Qian Wang

作者机构

• National Glycoengineering Research Center, Shandong University, Qingdao 266237, P. R. China.
• State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, P. R. China.
• Zhejiang Key Laboratory of Medical Epigenetics, Institute of Aging Research, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou 311121, P. R. China.

技术路线

数据/样本：20种sup-tRNA变体；分析：比较变体读通效率，归纳设计规则（反密码子与CUA相似性）；应用：LacI生物传感器、pykA/pykF调控的N-乙酰神经氨酸合成；验证：原文未报告独立正交性或脱靶验证

最近 5 个完整年度引用趋势

完整作者

Shengkun Tong、Yuxi Qin、Yaqian Sun、Yaojie Gao、Muyi Song、Tao Fang、Yaojun Tong

作者机构

• State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
• State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China. yaojun.tong@sjtu.edu.cn.

技术路线

理性蛋白质工程（截短柔性区）构建减毒Cas13d变体 → 生长密度与转录本敲低评估

最近 5 个完整年度引用趋势

完整作者

Ralf Tambets、Mihkel Jesse、Jaanika Kronberg、Adriaan van der Graaf、Erik Abner、Urmo Võsa、Ida Rahu、Nele Taba、Anastassia Kolde、Dzvenymyra Yarish、Sariyya Abdullayeva、Anastasiia Alekseienko、Andres Veidenberg、Estonian Biobank Research Team、Krista Fischer、Zoltán Kutalik、Tõnu Esko、Kaur Alasoo、Priit Palta

作者机构

• Institute of Computer Science, University of Tartu, Tartu, Estonia.
• Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
• Institute of Mathematics and Statistics, University of Tartu, Tartu, Estonia.
• Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
• University Center for Primary Care and Public Health, Unisanté, University of Lausanne, Lausanne, Switzerland.
• Institute of Computer Science, University of Tartu, Tartu, Estonia. kaur.alasoo@ut.ee.
• Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia. priit.palta@ut.ee.

技术路线

Estonian Biobank与UK Biobank共619,372名个体的249项循环代谢特征 → GWAS荟萃分析

最近 5 个完整年度引用趋势

完整作者

Juraj Gottweis、Wei-Hung Weng、Alexander Daryin、Tao Tu、Petar Sirkovic、Artiom Myaskovsky、Grzegorz Glowaty、Felix Weissenberger、Alessio Orlandi、Dan Popovici、Anil Palepu、Keran Rong、Ryutaro Tanno、Khaled Saab、Fan Zhang、Jacob Blum、Andrew Carroll、Kavita Kulkarni、Nenad Tomašev、Dina Zverinski、Ivor Rendulic、Elahe Vedadi、Florian Hasler、Luka Rimanic、Marina Boia、Ivan Budiselic、Ben Feinstein、Mathias Bellaiche、Tom Sheffer、Jan Freyberg、Jeremy Ratcliff、Ottavia Bertolli、Katherine Chou、Avinatan Hassidim、Burak Gokturk、Amin Vahdat、Yuan Guan、Vikram Dhillon、Eeshit Dhaval Vaishnav、Byron Lee、Tiago R D Costa、José R Penadés、Gary Peltz、Yossi Matias、James Manyika、Demis Hassabis、Yunhan Xu、Pushmeet Kohli、Annalisa Pawlosky、Alan Karthikesalingam、Vivek Natarajan

作者机构

• Google Cloud AI Research, Zurich, Switzerland. juro@google.com.
• Google DeepMind, Mountain View, CA, USA. ckbjimmy@google.com.
• Google Cloud AI Research, Zurich, Switzerland.
• Google DeepMind, Mountain View, CA, USA.
• Google Research, Mountain View, CA, USA.
• Stanford University School of Medicine, Palo Alto, CA, USA.
• Houston Methodist Hospital, Houston, TX, USA.
• Sequome, San Francisco, CA, USA.
• Fleming Initiative and Imperial College London, London, UK.
• Google DeepMind, Mountain View, CA, USA. pushmeet@google.com.
• Google Research, Mountain View, CA, USA. apawlosky@google.com.
• Google DeepMind, Mountain View, CA, USA. alankarthi@google.com.
• Google DeepMind, Mountain View, CA, USA. natviv@google.com.

技术路线

研究目标与科学证据输入→多智能体（基于Gemini）异步任务执行与锦标赛演化生成/批判/优化假设→自动化评估（测试时算力扩展）→三个生物医学应用（药物重定位、新靶点发现、抗菌素耐药机制解释）→急性髓系白血病候选药物与协同组合的体外实验验证

最近 5 个完整年度引用趋势

完整作者

Simran Gambhir、Shweta Pandey、Harsh Bajetha、Jasleen Kaur、Ankita Das、Gnanasekar Pranavathiyani、Rupali Aggarwal、Upasana Maity、Suhani Dange、Vipin Singh、Mayur Zarkar、Raghav Sankhdher、Bhupender Singh、Shivani Seth、Anshu Bhardwaj

作者机构

• Bioinformatics Centre, CSIR-Institute of Microbial Technology, Chandigarh 160036, India.
• Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
• UM-DAE Centre for Excellence in Basic Sciences, School of Biological Sciences, University of Mumbai Kalina Campus, Mumbai 400098, India.
• Life Sciences Department, J.C. Bose University of Science and Technology, YMCA, Sector 6, Mathura road, Faridabad Haryana 121006, India.
• Independent Researcher, IMTECH Housing, Sector 39A, Chandigarh 160036, India.

技术路线

数据/样本：聚焦WHO细菌优先病原体的参考基因组、泛基因组、AST谱、转录组数据集及多类注释资源（ARG、毒力因子、结构、宿主-病原互作、BGC、药物靶点等） → 分析：使用自建流程进行数据分析和注释，并按CLSI AST标准、EUCAST基因组序列指南及FAIR原则进行质量检查与人工整理

最近 5 个完整年度引用趋势

完整作者

Khoa Ngo、Pei-Chi Yang、Vladimir Yarov-Yarovoy、Colleen E Clancy、Igor Vorobyov

作者机构

• Center for Precision Medicine and Data Science, University of California, Davis, Davis, United States.
• Department of Physiology and Membrane Biology, University of California, Davis, Davis, United States.
• Department of Anesthesiology and Pain Medicine, University of California, Davis, Davis, United States.
• Department of Pharmacology, University of California, Davis, Davis, United States.

技术路线

结构模板引导AlphaFold预测hERG通道不同构象状态→与实验数据（状态依赖性结构特征、分子对接药物相互作用、分子动力学离子传导特性）比较验证→利用预测状态进行计算筛选并与实验药物亲和力比较→映射闭合/开放/失活态的残基相互作用网络，关键残基由既往突变研究验证

最近 5 个完整年度引用趋势

完整作者

Josephine Yates、Eliezer M Van Allen

作者机构

• Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Institute for Machine Learning, Department of Computer Science, ETH Zürich, Zurich, Switzerland; ETH AI Center, ETH Zurich, Zurich, Switzerland; Swiss Institute for Bioinformatics (SIB), Lausanne, Switzerland.
• Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Division of Medical Sciences, Harvard University, Boston, MA, USA; Parker Institute for Cancer Immunotherapy, Dana-Farber Cancer Institute, Boston, MA, USA. Electronic address: eliezerm_vanallen@dfci.harvard.edu.

技术路线

多组学数据集（单细胞与空间 profiling 数据） → AI 计算分析（细胞异质性、肿瘤微环境互作、靶点发现、生物标志物识别、患者分层、治疗反应预测、AI 辅助诊断）

最近 5 个完整年度引用趋势