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The 3.5-Å CryoEM Structure of Nanodisc-Reconstituted Yeast Vacuolar ATPase V_o Proton Channel

Molecular Cell 2018年第6期69卷 993-1004.e3页

作者： Roh, Soung-Hun Stam, Nicholas J. Hryc, Corey F. Couoh-Cardel, Sergio Pintilie, Grigore Chiu, Wah Wilkens, Stephan Department of Bioengineering and James H. Clark Center Stanford University Stanford 94305 CA United States Biosciences Division SLAC National Accelerator Laboratory Menlo Park 94025 CA United States Department of Biochemistry and Molecular Biology SUNY Upstate Medical University Syracuse 13210 NY United States Graduate Program in Quantitative and Computational Biosciences Baylor College of Medicine Houston 77030 TX United States Verna and Marrs McLean Department of Biochemistry and Molecular Biology Baylor College of Medicine Houston 77030 TX United States

The molecular mechanism of transmembrane proton translocation in rotary motor ATPases is not fully understood. Here, we report the 3.5-Å resolution cryoEM structure of the lipid nanodisc-reconstituted V_o proton channel of the yeast vacuolar H⁺-ATPase, captured in a physiologically relevant, autoinhibited state. The resulting atomic model provides structural detail for the amino acids that constitute the proton pathway at the interface of the proteolipid ring and subunit a. Based on the structure and previous mutagenesis studies, we propose the chemical basis of transmembrane proton transport. Moreover, we discovered that the C terminus of the assembly factor Voa1 is an integral component of mature V_o. Voa1’s C-terminal transmembrane α helix is bound inside the proteolipid ring, where it contributes to the stability of the complex. Our structure rationalizes possible mechanisms by which mutations in human V_o can result in disease phenotypes and may thus provide new avenues for therapeutic interventions. Here, we report the 3.5-Å resolution cryoEM structure of lipid nanodisc-reconstituted yeast vacuolar H⁺-ATPase V_o proton channel. The resulting atomic model provides insight into the chemical basis of transmembrane proton transport. Moreover, we discovered that the C terminus of the assembly factor Voa1 is an integral component of mature V_o. © 2018 Elsevier Inc.

关键词： cryoEM lipid nanodisc membrane protein structure proton pumping reversible disassembly V-ATPase assembly Vo proton channel vacuolar H+-ATPase Voa1

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An oncogenic enhancer encodes selective selenium dependency (vol 29, 386.e1, 2022)

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CELL STEM CELL 2022年第4期29卷 650-650页

作者： Eagle, Kenneth Jiang, Yajian Shi, Xiangguo Li, Minhua Obholzer, Nikolaus P. Hu, Tianyuan Perez, Monika W. Koren, Jost Vrabic Kitano, Ayumi Yi, Joanna S. Lin, Charles Y. Nakada, Daisuke Department of Molecular and Human Genetics Baylor College of Medicine 1 Baylor Plaza Houston TX 77030 USA Program in Quantitative and Computational Biosciences Baylor College of Medicine 1 Baylor Plaza Houston TX 77030 USA Program in Developmental Biology Baylor College of Medicine 1 Baylor Plaza Houston TX 77030 USA Development Disease Models & Therapeutics Graduate Program Baylor College of Medicine 1 Baylor Plaza Houston TX 77030 USA Department of Pediatrics Baylor College of Medicine 1 Baylor Plaza Houston TX 77030 USA Texas Children's Cancer and Hematology Centers 1102 Bates Avenue Houston TX 77030 USA Therapeutic Innovation Center Verna and Marrs McLean Department of Biochemistry and Molecular Biology Baylor College of Medicine 1 Baylor Plaza Houston TX 77030 USA Dan L. Duncan Comprehensive Cancer Center Baylor College of Medicine 1 Baylor Plaza Houston TX 77030 USA Kronos Bio 301 Binney St. 2nd Floor East Cambridge MA 02139 USA

Deregulation of transcription is a hallmark of acute myeloid leukemia (AML) that drives oncogenic expression programs and presents opportunities for therapeutic targeting. By integrating comprehensive pan-cancer enhancer landscapes with genetic dependency mapping, we find that AML-enriched enhancers encode for more selective tumor dependencies. We hypothesized that this approach could identify actionable dependencies downstream of oncogenic driver events and discovered a MYB-regulated AML-enriched enhancer regulating SEPHS2 , a key component of the selenoprotein production pathway. Using a combination of patient samples and mouse models, we show that this enhancer upregulates SEPHS2 , promoting selenoprotein production and antioxidant function required for AML survival. SEPHS2 and other selenoprotein pathway genes are required for AML growth in vitro . SEPHS2 knockout and selenium dietary restriction significantly delay leukemogenesis in vivo with little effect on normal hematopoiesis. These data validate the utility of enhancer mapping in target identification and suggest that selenoprotein production is an actionable target in AML.

关键词： AML selenium enhancer MYB SEPHS2 hematopoiesis hematopoietic stem cell leukemia stem cell selenocysteine

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Correction: Single-cell multi-omics integration for unpaired data by a siamese network with graph-based contrastive loss

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BMC bioinformatics 2023年第1期24卷 123页

作者： Chaozhong Liu Linhua Wang Zhandong Liu Graduate Program in Quantitative and Computational Biosciences Baylor College of Medicine Houston USA. Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital Houston USA. zhandong.liu@bcm.edu. Department of Pediatrics Baylor College of Medicine Houston USA. zhandong.liu@bcm.edu.

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Publisher Correction: Paternal restraint stress affects offspring metabolism via ATF-2 dependent mechanisms in Drosophila melanogaster germ cells

Communications biology

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Communications biology 2020年第1期3卷 251页

作者： Ki-Hyeon Seong Nhung Hong Ly Yuki Katou Naoko Yokota Ryuichiro Nakato Shinnosuke Murakami Akiyoshi Hirayama Shinji Fukuda Siu Kang Tomoyoshi Soga Katsuhiko Shirahige Shunsuke Ishii RIKEN Cluster for Pioneering Research Tsukuba Ibaraki Japan. ki-hyeon.seong@riken.jp. PRESTO Japan Science and Technology Agency Kawaguchi Japan. ki-hyeon.seong@riken.jp. RIKEN Cluster for Pioneering Research Tsukuba Ibaraki Japan. Laboratory of Genome Structure and Function Institute for Quantitative Biosciences University of Tokyo Tokyo Japan. Laboratory of Computational Genomics Institute for Quantitative Biosciences University of Tokyo Tokyo Japan. Institute for Advanced Biosciences Keio University Tsuruoka Yamagata Japan. Systems Biology Program Graduate School of Media and Governance Keio University Fujisawa Kanagawa Japan. PRESTO Japan Science and Technology Agency Kawaguchi Japan. Transborder Medical Research Center University of Tsukuba Tsukuba Ibaraki Japan. Department of Bio-Systems Engineering Graduate School of Science and Engineering Yamagata University Yonezawa Yamagata Japan. RIKEN Cluster for Pioneering Research Tsukuba Ibaraki Japan. sishii@riken.jp.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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Author Correction: cfSNV: a software tool for the sensitive detection of somatic mutations from cell-free DNA

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Nature protocols 2024年第4期19卷 1289页

作者： Shuo Li Ran Hu Colin Small Ting-Yu Kang Chun-Chi Liu Xianghong Jasmine Zhou Wenyuan Li Department of Pathology and Laboratory Medicine David Geffen School of Medicine University of California at Los Angeles Los Angeles CA USA. Bioinformatics Interdepartmental Graduate Program University of California at Los Angeles Los Angeles CA USA. Institute for Quantitative & Computational Biosciences University of California at Los Angeles Los Angeles CA USA. EarlyDiagnostics Inc. Los Angeles CA USA. Department of Pathology and Laboratory Medicine David Geffen School of Medicine University of California at Los Angeles Los Angeles CA USA. XJZhou@mednet.ucla.edu. Institute for Quantitative & Computational Biosciences University of California at Los Angeles Los Angeles CA USA. XJZhou@mednet.ucla.edu. EarlyDiagnostics Inc. Los Angeles CA USA. XJZhou@mednet.ucla.edu. Department of Pathology and Laboratory Medicine David Geffen School of Medicine University of California at Los Angeles Los Angeles CA USA. WenyuanLi@mednet.ucla.edu. EarlyDiagnostics Inc. Los Angeles CA USA. WenyuanLi@mednet.ucla.edu.

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Publisher Correction: Comprehensive molecular characterization of mitochondrial genomes in human cancers

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Nature genetics 2023年第5期55卷 893页

作者： Yuan Yuan Young Seok Ju Youngwook Kim Jun Li Yumeng Wang Christopher J Yoon Yang Yang Inigo Martincorena Chad J Creighton John N Weinstein Yanxun Xu Leng Han Hyung-Lae Kim Hidewaki Nakagawa Keunchil Park Peter J Campbell Han Liang Department of Bioinformatics and Computational Biology The University of Texas MD Anderson Cancer Center Houston TX USA. Cancer Genome Project Wellcome Trust Sanger Institute Hinxton UK. Graduate School of Medical Science and Engineering Korea Advanced Institute of Science and Technology Daejeon Korea. Department of Health Science and Technology Samsung Advanced Institute for Health Science and Technology Sungkyunkwan University School of Medicine Seoul Korea. Quantitative and Computational Biosciences Graduate Program Baylor College of Medicine Houston TX USA. Division of Biostatistics The University of Texas Health Science Center at Houston School of Public Health Houston TX USA. Department of Medicine and Dan L. Duncan Cancer Center Division of Biostatistics Baylor College of Medicine Houston TX USA. Department of Systems Biology The University of Texas MD Anderson Cancer Center Houston TX USA. Department of Applied Mathematics and Statistics Johns Hopkins University Baltimore MD USA. Department of Biochemistry and Molecular Biology The University of Texas Health Science Center at Houston McGovern Medical School Houston TX USA. Department of Biochemistry Ewha Womans University School of Medicine Seoul Korea. Laboratory for Cancer Genomics RIKEN Center for Integrative Medical Sciences Yokohama Japan. Division of Hematology/Oncology Samsung Medical Center Sungkyunkwan University School of Medicine Seoul Korea. kpark@skku.edu. Cancer Genome Project Wellcome Trust Sanger Institute Hinxton UK. pc8@sanger.ac.uk. Cambridge University Hospitals NHS Foundation Trust Cambridge UK. pc8@sanger.ac.uk. Department of Bioinformatics and Computational Biology The University of Texas MD Anderson Cancer Center Houston TX USA. hliang1@***. Quantitative and Computational Biosciences Graduate Program Baylor College of Medicine Houston TX USA. hliang1@***. Department of Systems Biology The University of Texas MD Anderson Cancer Center Houston TX USA. hliang1@mdanderson

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International Society for Extracellular Vesicles workshop. QuantitatEVs: Multiscale analyses, from bulk to single extracellular vesicle

Journal of Extracellular Biology

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Journal of Extracellular Biology 2024年第1期3卷 e137页

作者： Basso, Manuela Gori, Alessandro Nardella, Caterina Palviainen, Mari Holcar, Marija Sotiropoulos, Ioannis Bobis-Wozowicz, Sylwia Casarotto, Elena Ciani, Yari Suetsugu, Shiro Gualerzi, Alice Martin-Jaular, Lorena Boselli, Daniela Kashkanova, Anna Parisse, Pietro Lippens, Lien Pagliuca, Martina Blessing, Martin Frigerio, Roberto Fourniols, Thibaut Meliciano, Ana Fietta, Anna Fioretti, Paolo Vincenzo Soroczyńska, Karolina Picciolini, Silvia Salviano-Silva, Amanda Bergese, Paolo Zocco, Davide Chiari, Marcella Jenster, Guido Waldron, Levi Milosavljevic, Aleksandar Nolan, John Monopoli, Marco P. Witwer, Kenneth W. Bussolati, Benedetta Di Vizio, Dolores Falcon Perez, Juan Lenassi, Metka Cretich, Marina Demichelis, Francesca Department of Cellular Computational and Integrative Biology (CIBIO) University of Trento Trento Italy National Research Council of Italy Istituto di Scienze e Tecnologie Chimiche (SCITEC-CNR) Milan Italy EV group Molecular and Integrative Biosciences Research Program Faculty of Biological and Environmental Sciences University of Helsinki Helsinki Finland Institute of Biochemistry and Molecular Genetics Faculty of Medicine University of Ljubljana Ljubljana Slovenia Institute of Biosciences & Applications National Center for Scientific Research (NCSR) Demokritos Paraskevi Greece Faculty of Biochemistry Biophysics and Biotechnology Department of Cell Biology Jagiellonian University Krakow Poland Dipartimento di Scienze Farmacologiche e Biomolecolari “Rodolfo Paoletti” (DiSFeB) Dipartimento di Eccellenza Università degli Studi di Milano Milan Italy Division of Biological Science Graduate School of Science and Technology Nara Institute of Science and Technology Ikoma Japan IRCCS Fondazione Don Carlo Gnocchi Milan Italy Institut Curie PSL University Inserm U932 Immunity and Cancer Paris France FRACTAL (Flow Cytometry Resource Advanced Cytometry Technical Applications Laboratory) San Raffaele Scientific Institute Milan Italy Max Planck Institute for the Science of Light Erlangen Germany National Research Council of Italy Istituto Officina dei Materiali (IOM-CNR) Trieste Italy Department of Human Structure and Repair Laboratory of Experimental Cancer Research Ghent University Ghent Belgium Cancer Research Institute Ghent Ghent Belgium Molecular Predictors and New Targets in Oncology Gustave Roussy Villejuif France Clinical and Translational Oncology Scuola Superiore Meridionale Naples Italy EverZom Paris France iBET-Instituto de Biologia Experimental e Tecnológica Oeiras Portugal Department of Biomedical Sciences (DSB) University of Padua Padua Italy Fondazione Istituto di Ricerca Pediatrica Città della Speranza (IRP) Padua Italy Medical University of

The “QuantitatEVs: multiscale analyses, from bulk to single vesicle” workshop aimed to discuss quantitative strategies and harmonized wet and computational approaches toward the comprehensive analysis of extracellular vesicles (EVs) from bulk to single vesicle analyses with a special focus on emerging technologies. The workshop covered the key issues in the quantitative analysis of different EV-associated molecular components and EV biophysical features, which are considered the core of EV-associated biomarker discovery and validation for their clinical translation. The in-person-only workshop was held in Trento, Italy, from January 31^st to February 2^nd, 2023, and continued in Milan on February 3^rd with “Next Generation EVs,” a satellite event dedicated to early career researchers (ECR). This report summarizes the main topics and outcomes of the workshop. © 2024 The Authors. Journal of Extracellular Biology published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.

关键词： multiomics analysis multiscale analysis quantitative biology single vesicle

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Author Correction: Comprehensive molecular characterization of mitochondrial genomes in human cancers

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Nature genetics 2023年第6期55卷 1078页

作者： Yuan Yuan Young Seok Ju Youngwook Kim Jun Li Yumeng Wang Christopher J Yoon Yang Yang Inigo Martincorena Chad J Creighton John N Weinstein Yanxun Xu Leng Han Hyung-Lae Kim Hidewaki Nakagawa Keunchil Park Peter J Campbell Han Liang Department of Bioinformatics and Computational Biology The University of Texas MD Anderson Cancer Center Houston TX USA. Cancer Genome Project Wellcome Trust Sanger Institute Hinxton UK. Graduate School of Medical Science and Engineering Korea Advanced Institute of Science and Technology Daejeon Korea. Department of Health Science and Technology Samsung Advanced Institute for Health Science and Technology Sungkyunkwan University School of Medicine Seoul Korea. Samsung Genome Institute Samsung Medical Center Seoul Korea. Quantitative and Computational Biosciences Graduate Program Baylor College of Medicine Houston TX USA. Division of Biostatistics The University of Texas Health Science Center at Houston School of Public Health Houston TX USA. Department of Medicine and Dan L. Duncan Cancer Center Division of Biostatistics Baylor College of Medicine Houston TX USA. Department of Systems Biology The University of Texas MD Anderson Cancer Center Houston TX USA. Department of Applied Mathematics and Statistics Johns Hopkins University Baltimore MD USA. Department of Biochemistry and Molecular Biology The University of Texas Health Science Center at Houston McGovern Medical School Houston TX USA. Department of Biochemistry Ewha Womans University School of Medicine Seoul Korea. Laboratory for Cancer Genomics RIKEN Center for Integrative Medical Sciences Yokohama Japan. Division of Hematology/Oncology Samsung Medical Center Sungkyunkwan University School of Medicine Seoul Korea. kpark@skku.edu. Samsung Advanced Institute for Health Sciences and Technology Sungkyunkwan University School of Medicine Seoul South Korea. kpark@skku.edu. Cancer Genome Project Wellcome Trust Sanger Institute Hinxton UK. pc8@sanger.ac.uk. Department of Haematology University of Cambridge Cambridge UK. pc8@sanger.ac.uk. Department of Bioinformatics and Computational Biology The University of Texas MD Anderson Cancer Center Houston TX USA. hliang1@mdanderson.org. Quantitative and Comp

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Author Correction: Profiling immunoglobulin repertoires across multiple human tissues using RNA sequencing

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Nature communications 2020年第1期11卷 4499页

作者： Igor Mandric Jeremy Rotman Harry Taegyun Yang Nicolas Strauli Dennis J Montoya William Van Der Wey Jiem R Ronas Benjamin Statz Douglas Yao Velislava Petrova Alex Zelikovsky Roberto Spreafico Sagiv Shifman Noah Zaitlen Maura Rossetti K Mark Ansel Eleazar Eskin Serghei Mangul Department of Computer Science University of California Los Angeles 404 Westwood Plaza Los Angeles CA 90095 USA. Department of Clinical Pharmacy School of Pharmacy University of Southern California 1540 Alcazar Street Los Angeles CA 90033 USA. Bioinformatics Interdepartmental Ph.D. Program University of California Los Angeles 611 Charles E. Young Drive East Los Angeles CA 90095-1570 USA. Biomedical Sciences Graduate Program University of California San Francisco 1675 Owens Street Suite 310 San Francisco CA 94143-0523 USA. Department of Molecular Cell and Developmental Biology University of California Los Angeles 610 Charles E. Young Drive South Los Angeles CA 90095 USA. Department of Microbiology Immunology and Molecular Genetics University of California Los Angeles 609 Charles E. Young Drive East Los Angeles CA 90095 USA. Program in Bioinformatics and Integrative Genomics Harvard Medical School 10 Shattuck Street Suite 514 Boston MA 02115 USA. Wellcome Trust Sanger Institute Wellcome Genome Campus Hinxton Cambridge CB10 1SA UK. Department of Computer Science Georgia State University 33 Gilmer Street SE Atlanta GA 30303 USA. The Laboratory of Bioinformatics I.M. Sechenov First Moscow State Medical University Moscow 119991 Russia. Institute for Quantitative and Computational Biosciences University of California Los Angeles 611 Charles E. Young Drive East Los Angeles CA 90095 USA. Department of Genetics The Institute of Life Sciences The Hebrew University of Jerusalem Jerusalem 9190401 Israel. Department of Medicine University of California San Francisco 533 Parnassus Avenue San Francisco CA 94143 USA. Immunogenetics Center Department of Pathology and Laboratory Medicine David Geffen School of Medicine University of California Los Angeles 1000 Veteran Avenue Los Angeles CA 90095-1652 USA. Sandler Asthma Basic Research Center Department of Microbiology and Immunology University of California San Francisco 513 Parnass

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

关键词： computational biology and bioinformatics Adaptive immunity Immunogenetics B cells

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Author Correction: Genomic footprints of activated telomere maintenance mechanisms in cancer (Dec, 10.1038/s41467-019-13824-9, 2022)

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NATURE COMMUNICATIONS 2022年第1期13卷 1-1页

作者： Sieverling, Lina Hong, Chen Koser, Sandra D. Ginsbach, Philip Kleinheinz, Kortine Hutter, Barbara Braun, Delia M. Cortes-Ciriano, Isidro Xi, Ruibin Kabbe, Rolf Park, Peter J. Eils, Roland Schlesner, Matthias Brors, Benedikt Rippe, Karsten Jones, David T. W. Feuerbach, Lars Division of Applied Bioinformatics German Cancer Research Center (DKFZ) 69120 Heidelberg Germany Faculty of Biosciences Heidelberg University 69120 Heidelberg Germany Division of Applied Bioinformatics German Cancer Research Center (DKFZ) Heidelberg Germany Faculty of Biosciences Heidelberg University Heidelberg Germany Division of Theoretical Bioinformatics German Cancer Research Center (DKFZ) 69120 Heidelberg Germany Department for Bioinformatics and Functional Genomics Institute for Pharmacy and Molecular Biotechnology (IPMB) and BioQuant 69120 Heidelberg Germany Division of Theoretical Bioinformatics German Cancer Research Center (DKFZ) Heidelberg Germany Institute of Pharmacy and Molecular Biotechnology and BioQuant Heidelberg University Heidelberg Germany German Cancer Consortium (DKTK) Heidelberg Germany National Center for Tumor Diseases (NCT) Heidelberg Heidelberg Germany Heidelberg Center for Personalized Oncology (DKFZ-HIPO) German Cancer Research Center (DKFZ) Heidelberg Germany German Cancer Consortium (DKTK) German Cancer Research Center (DKFZ) Heidelberg Germany Division of Chromatin Networks German Cancer Research Center (DKFZ) and BioQuant 69120 Heidelberg Germany Department of Biomedical Informatics Harvard Medical School Boston Massachusetts 02115 USA Department of Chemistry Centre for Molecular Science Informatics University of Cambridge Cambridge CB2 1EW UK Ludwig Center at Harvard Medical School Boston Massachusetts 02115 USA Department of Biomedical Informatics Harvard Medical School Boston MA USA Department of Chemistry Centre for Molecular Science Informatics University of Cambridge Cambridge UK Ludwig Center at Harvard Medical School Boston MA USA School of Mathematical Sciences and Center for Statistical Science Peking University Beijing 100871 China Heidelberg University Heidelberg Germany New BIH Digital Health Center Berlin Institute of Health (BIH) and Charité - Universitätsmedizin Berlin Berlin Germany Bioi

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