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arXiv 2019年

作者： Jia, Dongya Li, Xuefei Bocci, Federico Tripathi, Shubham Deng, Youyuan Jolly, Mohit Kumar Onuchic, José N. Levine, Herbert Center for Theoretical Biological Physics Rice University HoustonTX77005 United States Department of Chemistry Rice University HoustonTX77005 United States Program in Systems Synthetic and Physical Biology Rice University HoustonTX77005 United States Program in Applied Physics Rice University HoustonTX77005 United States Centre for BioSystems Science and Engineering Indian Institute of Science Bangalore560012 India Department of Biosciences Rice University HoustonTX77005 United States Department of Physics and Astronomy Rice University HoustonTX77005 United States Department of Bioengineering Northeastern University BostonMA02115 United States Department of Physics Northeastern University BostonMA02115 United States

Cancer cells can acquire a spectrum of stable hybrid epithelial/mesenchymal (E/M) states during epithelial-mesenchymal transition (EMT). Cells in these hybrid E/M phenotypes often combine epithelial and mesenchymal features and tend to migrate collectively commonly as small clusters. Such collectively migrating cancer cells play a pivotal role in seeding metastases and their presence in cancer patients indicates an adverse prognostic factor. Moreover, cancer cells in hybrid E/M phenotypes tend to be more associated with stemness which endows them with tumor-initiation ability and therapy resistance. Most recently, cells undergoing EMT have been shown to promote immune suppression for better survival. A systematic understanding of the emergence of hybrid E/M phenotypes and the connection of EMT with stemness and immune suppression would contribute to more effective therapeutic strategies. In this review, we first discuss recent efforts combining theoretical and experimental approaches to elucidate mechanisms underlying EMT multi-stability (i.e. the existence of multiple stable phenotypes during EMT) and the properties of hybrid E/M phenotypes. Following we discuss non-cell-autonomous regulation of EMT by cell cooperation and extracellular matrix. Afterwards, we discuss various metrics that can be used to quantify EMT spectrum. We further describe possible mechanisms underlying the formation of clusters of circulating tumor cells. Last but not least, we summarize recent systems biology analysis of the role of EMT in the acquisition of stemness and immune suppression. Copyright © 2019, The Authors. All rights reserved.

关键词： Cells

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Serotonin transporter inhibits antitumor immunity through regulating the intratumoral serotonin axis

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Cell 2025年

作者： Li, Bo Elsten-Brown, James Li, Miao Zhu, Enbo Li, Zhe Chen, Yuning Kang, Elliot Ma, Feiyang Chiang, Jennifer Li, Yan-Ruide Zhu, Yichen Huang, Jie Fung, Audrey Scarborough, Quentin Cadd, Robin Zhou, Jin J. Chin, Arnold I. Pellegrini, Matteo Yang, Lili Department of Microbiology Immunology and Molecular Genetics University of California Los Angeles Los Angeles 90095 CA United States Department of Materials Science and Engineering University of California Los Angeles Los Angeles 90095 CA United States Department of Molecular Cell and Developmental Biology University of California Los Angeles Los Angeles 90095 CA United States Department of Biostatistics Fielding School of Public Health University of California Los Angeles Los Angeles CA United States Department of Urology University of California Los Angeles Los Angeles 90095 CA United States Eli & Edythe Broad Center of Regenerative Medicine and Stem Cell Research University of California Los Angeles Los Angeles 90095 CA United States Jonsson Comprehensive Cancer Center David Geffen School of Medicine University of California Los Angeles Los Angeles 90095 CA United States Bioinformatics Interdepartmental Program University of California Los Angeles Los Angeles 90095 CA United States Institute for Quantitative and Computational Biosciences-The Collaboratory University of California Los Angeles Los Angeles 90095 CA United States Department of Bioengineering University of California Los Angeles Los Angeles 90095 CA United States Goodman-Luskin Microbiome Center University of California Los Angeles Los Angeles 90095 CA United States Molecular Biology Institute University of California Los Angeles Los Angeles 90095 CA United States Parker Institute for Cancer Immunotherapy University of California Los Angeles Los Angeles 90095 CA United States

Identifying additional immune checkpoints hindering antitumor T cell responses is key to the development of next-generation cancer immunotherapies. Here, we report the induction of serotonin transporter (SERT), a regulator of serotonin levels and physiological functions in the brain and peripheral tissues, in tumor-infiltrating CD8 T cells. Inhibition of SERT using selective serotonin reuptake inhibitors (SSRIs), the most widely prescribed antidepressants, significantly suppressed tumor growth and enhanced T cell antitumor immunity in various mouse syngeneic and human xenograft tumor models. Importantly, SSRI treatment exhibited significant therapeutic synergy with programmed cell death protein 1 (PD-1) blockade, and clinical data correlation studies negatively associated intratumoral SERT expression with patient survival in a range of cancers. Mechanistically, SERT functions as a negative-feedback regulator inhibiting CD8 T cell reactivities by depleting intratumoral T cell-autocrine serotonin. These findings highlight the significance of the intratumoral serotonin axis and identify SERT as an immune checkpoint, positioning SSRIs as promising candidates for cancer immunotherapy. © 2025 The Authors

关键词： antidepressants cancer immunotherapy immune checkpoint intratumoral serotonin axis PD-1 blockade serotonin serotonin transporter SSRIs T cell antitumor immunity tumor microenvironment

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

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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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Large-scale production of extracellular vesicles: Report on the “massivEVs” ISEV workshop

Journal of Extracellular Biology

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Journal of Extracellular Biology 2022年第10期1卷 e63页

作者： Paolini, Lucia Monguió-Tortajada, Marta Costa, Marta Antenucci, Fabio Barilani, Mario Clos-Sansalvador, Marta Andrade, André Cronemberger Driedonks, Tom A. P. Giancaterino, Sara Kronstadt, Stephanie M. Mizenko, Rachel R. Nawaz, Muhammad Osteikoetxea, Xabier Pereira, Carla Shrivastava, Surya Boysen, Anders Toftegaard van de Wakker, Simonides Immanuel van Herwijnen, Martijn J. C. Wang, Xiaoqin Watson, Dionysios C. Gimona, Mario Kaparakis-Liaskos, Maria Konstantinov, Konstantin Lim, Sai Kiang Meisner-Kober, Nicole Stork, Michiel Nejsum, Peter Radeghieri, Annalisa Rohde, Eva Touzet, Nicolas Wauben, Marca H. M. Witwer, Kenneth W. Bongiovanni, Antonella Bergese, Paolo Department of Molecular and Translational Medicine University of Brescia Brescia Italy Center for Colloid and Surface Science (CSGI) Department of Chemistry University of Florence Sesto Fiorentino (FI) Italy Department of Medical and Surgical Specialties Radiological Sciences and Public Health University of Brescia Brescia Italy CREC Research Program Health Science Research Institute Germans Trias i Pujol (IGTP) Badalona Spain Heart Institute (iCor) Cardiology Department Germans Trias i Pujol University Hospital Badalona Spain iBET Instituto de Biologia Experimental e Tecnológica Oeiras Portugal Instituto de Tecnologia Química e Biológica António Xavier Universidade Nova de Lisboa Oeiras Portugal Department of Veterinary and Animal Sciences University of Copenhagen Copenhagen Denmark Laboratory of Regenerative Medicine ‒ Cell Factory Department of Transfusion Medicine and Hematology Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano Italy REMAR-IGTP Group Germans Trias i Pujol Research Institute (IGTP) & Nephrology Department University Hospital Germans Trias i Pujol (HUGTiP) Catalonia Badalona (Barcelona) Spain Department of Cell Biology Physiology and Immunology Universitat Autònoma de Barcelona (UAB) Bellaterra Spain Experimental and Clinical Cell Therapy Institute (ExCT) Spinal Cord Injury and Tissue Regeneration Center Paracelsus Medical University Salzburg Austria CDL Research University Medical Center Utrecht Utrecht University Utrecht Netherlands Department of Molecular and Comparative Pathology Johns Hopkins School of Medicine Baltimore MD United States Department of Civil Chemical Environmental and Materials Engineering Alma Mater Studiorum University of Bologna Bologna Italy Fischell Department of Bioengineering University of Maryland College Park MD United States Department of Biomedical Engineering University of California Davis CA United States Department of Rheumatology and Inflammation Research Institute of Medicine

Extracellular vesicles (EVs) large-scale production is a crucial point for the translation of EVs from discovery to application of EV-based products. In October 2021, the International Society for Extracellular Vesicles (ISEV), along with support by the FET-OPEN projects, “The Extracellular Vesicle Foundry” (evFOUNDRY) and “Extracellular vesicles from a natural source for tailor-made nanomaterials” (VES4US), organized a workshop entitled “massivEVs” to discuss the potential challenges for translation of EV-based products. This report gives an overview of the topics discussed during “massivEVs”, the most important points raised, and the points of consensus reached after discussion among academia and industry representatives. Overall, the review of the existing EV manufacturing, upscaling challenges and directions for their resolution highlighted in the workshop painted an optimistic future for the expanding EV field. © 2022 The Authors. Journal of Extracellular Biology published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.

关键词： EV-based products extracellular vesicles ISEV workshop large-scale production manufacturing processing regulatory issues

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Author Correction: Greengenes2 unifies microbial data in a single reference tree

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Nature biotechnology 2024年第5期42卷 813页

作者： Daniel McDonald Yueyu Jiang Metin Balaban Kalen Cantrell Qiyun Zhu Antonio Gonzalez James T Morton Giorgia Nicolaou Donovan H Parks Søren M Karst Mads Albertsen Philip Hugenholtz Todd DeSantis Se Jin Song Andrew Bartko Aki S Havulinna Pekka Jousilahti Susan Cheng Michael Inouye Teemu Niiranen Mohit Jain Veikko Salomaa Leo Lahti Siavash Mirarab Rob Knight Department of Pediatrics University of California San Diego School of Medicine La Jolla CA USA. Department of Electrical and Computer Engineering University of California San Diego La Jolla CA USA. Bioinformatics and Systems Biology Program University of California San Diego La Jolla CA USA. Department of Computer Science and Engineering University of California San Diego La Jolla CA USA. School of Life Sciences Arizona State University Tempe AZ USA. Biodesign Center for Fundamental and Applied Microbiomics Arizona State University Tempe AZ USA. Biostatistics & Bioinformatics Branch Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health Bethesda MD USA. Halicioglu Data Science Institute University of California San Diego La Jolla CA USA. Australian Centre for Ecogenomics School of Chemistry and Molecular Biosciences The University of Queensland St Lucia Queensland Australia. Department of Obstetrics and Gynecology Columbia University New York NY USA. Department of Chemistry and Bioscience Aalborg University Aalborg Denmark. Department of Informatics Second Genome Brisbane CA USA. Center for Microbiome Innovation Jacobs School of Engineering University of California San Diego La Jolla CA USA. Finnish Institute for Health and Welfare Helsinki Finland. Institute for Molecular Medicine Finland FIMM-HiLIFE Helsinki Finland. Division of Cardiology Brigham and Women's Hospital Boston MA USA. Cedars-Sinai Medical Center Los Angeles CA USA. Cambridge Baker Systems Genomics Initiative Baker Heart and Diabetes Institute Melbourne Victoria Australia. Cambridge Baker Systems Genomics Initiative Department of Public Health and Primary Care University of Cambridge Cambridge UK. Division of Medicine Turku University Hospital and University of Turku Turku Finland. Sapient Bioanalytics LLC San Diego CA USA. Department of Computing University of Turku Turku Finland. Department of Pediatrics Uni

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The repertoire of mutational signatures in human cancer (vol 578, pg 94, 2020)

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NATURE 2023年第7948期614卷 E41-E41页

作者： Alexandrov, Ludmil B. Kim, Jaegil Haradhvala, Nicholas J. Huang, Mi Ni Ng, Alvin Wei Tian Wu, Yang Boot, Arnoud Covington, Kyle R. Gordenin, Dmitry A. Bergstrom, Erik N. Islam, S. M. Ashiqul Lopez-Bigas, Nuria Klimczak, Leszek J. McPherson, John R. Morganella, Sandro Sabarinathan, Radhakrishnan Wheeler, David A. Mustonen, Ville Getz, Gad Rozen, Steven G. Stratton, Michael R. Department of Cellular and Molecular Medicine Department of Bioengineering Moores Cancer Center University of California San Diego CA USA Wellcome Sanger Institute Wellcome Genome Campus Hinxton UK Department of Cellular and Molecular Medicine and Department of Bioengineering University of California San Diego La Jolla CA USA UC San Diego Moores Cancer Center San Diego CA USA University of California San Diego San Diego CA USA Broad Institute of MIT and Harvard Cambridge MA USA Center for Cancer Research Massachusetts General Hospital Boston MA USA Massachusetts General Hospital Boston MA USA Department of Pathology Massachusetts General Hospital Boston MA USA Harvard Medical School Boston MA USA Laboratory for Medical Science Mathematics RIKEN Center for Integrative Medical Sciences Yokohama Japan Computational Biology Program Ontario Institute for Cancer Research Toronto ON Canada Programme in Cancer & Stem Cell Biology Duke-NUS Medical School Singapore Singapore Centre for Computational Biology Duke-NUS Medical School Singapore Singapore Programme in Cancer and Stem Cell Biology Duke-NUS Medical School Singapore Singapore Programme in Cancer and Stem Cell Biology Centre for Computational Biology Duke-NUS Medical School Singapore Singapore SingHealth Duke-NUS Institute of Precision Medicine National Heart Centre Singapore Singapore Singapore Cancer Science Institute of Singapore National University of Singapore Singapore Singapore Institute of Molecular and Cell Biology Singapore Singapore Laboratory of Cancer Epigenome Division of Medical Science National Cancer Centre Singapore Singapore Singapore Duke-NUS Medical School Singapore Singapore Human Genome Sequencing Center Baylor College of Medicine Houston TX USA Dan L. Duncan Cancer Center Baylor College of Medicine Houston TX USA Department of Molecular and Human Genetics Baylor College of Medicine Houston TX USA Genome Integrity and Structural Biology Laboratory National Ins

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Author Correction: On-chip recapitulation of clinical bone marrow toxicities and patient-specific pathophysiology

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Nature biomedical engineering 2020年第4期4卷 477页

作者： David B Chou Viktoras Frismantas Yuka Milton Rhiannon David Petar Pop-Damkov Douglas Ferguson Alexander MacDonald Özge Vargel Bölükbaşı Cailin E Joyce Liliana S Moreira Teixeira Arianna Rech Amanda Jiang Elizabeth Calamari Sasan Jalili-Firoozinezhad Brooke A Furlong Lucy R O'Sullivan Carlos F Ng Youngjae Choe Susan Marquez Kasiani C Myers Olga K Weinberg Robert P Hasserjian Richard Novak Oren Levy Rachelle Prantil-Baun Carl D Novina Akiko Shimamura Lorna Ewart Donald E Ingber Wyss Institute for Biologically Inspired Engineering Harvard University Boston MA USA. Department of Pathology Massachusetts General Hospital Boston MA USA. Clinical Pharmacology and Safety Sciences BioPharmaceuticals R&D AstraZeneca Cambridge UK. DMPK Oncology R&D AstraZeneca Boston MA USA. Clinical and Quantitative Pharmacology Clinical Pharmacology and Safety Sciences Pharmaceutical Sciences R&D AstraZeneca Cambridge UK. Dana Farber/Boston Children's Cancer and Blood Disorders Center Boston MA USA. Department of Cancer Immunology and Virology Dana-Farber Cancer Institute Boston MA USA. Department of Medicine Harvard Medical School Boston MA USA. Department of Chemical Engineering Loughborough University Loughborough UK. Vascular Biology Program and Department of Surgery Boston Children's Hospital and Harvard Medical School Boston MA USA. Department of Bioengineering and Institute for Bioengineering and Biosciences (iBB) Instituto Superior Técnico Universidade de Lisboa Lisbon Portugal. Department of Pediatrics University of Cincinnati College of Medicine Cincinnati OH USA. Division of Bone Marrow Transplantation and Immune Deficiency Cincinnati Children's Hospital Cincinnati OH USA. Department of Pathology Boston Children's Hospital Boston MA USA. Broad Institute of Harvard and MIT Cambridge MA USA. Wyss Institute for Biologically Inspired Engineering Harvard University Boston MA USA. don.ingber@wyss.harvard.edu. Vascular Biology Program and Department of Surgery Boston Children's Hospital and Harvard Medical School Boston MA USA. don.ingber@wyss.harvard.edu. Harvard John A. Paulson School of Engineering and Applied Sciences Cambridge MA USA. don.ingber@wyss.harvard.edu.

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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Patterns of somatic structural variation in human cancer genomes (vol 578, pg 112, 2020)

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NATURE 2023年第7948期614卷 E38-E38页

作者： Li, Yilong Roberts, Nicola D. Wala, Jeremiah A. Shapira, Ofer Schumacher, Steven E. Kumar, Kiran Khurana, Ekta Waszak, Sebastian Korbel, Jan O. Haber, James E. Imielinski, Marcin Weischenfeldt, Joachim Beroukhim, Rameen Campbell, Peter J. Cancer Genome Project Wellcome Trust Sanger Institute Hinxton UK Totient Inc Cambridge MA USA Wellcome Sanger Institute Wellcome Genome Campus Hinxton UK Department of Haematology University of Cambridge Cambridge UK Cambridge University Hospitals NHS Foundation Trust Cambridge UK Korea Advanced Institute of Science and Technology Daejeon South Korea Department of Zoology Genetics and Physical Anthropology University of Santiago de Compostela Santiago de Compostela Spain Centre for Research in Molecular Medicine and Chronic Diseases (CIMUS) University of Santiago de Compostela Santiago de Compostela Spain The Biomedical Research Centre (CINBIO) University of Vigo Vigo Spain Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS) Universidade de Santiago de Compostela Santiago de Compostela Spain Department of Zoology Genetics and Physical Anthropology (CiMUS) Universidade de Santiago de Compostela Santiago de Compostela Spain The Biomedical Research Centre (CINBIO) Universidade de Vigo Vigo Spain The Broad Institute of Harvard and MIT Cambridge MA USA Bioinformatics and Integrative Genomics Harvard University Cambridge MA USA Department of Cancer Biology Dana-Farber Cancer Institute Boston MA USA Broad Institute of MIT and Harvard Cambridge MA USA Department of Medical Oncology Dana-Farber Cancer Institute Boston MA USA Harvard Medical School Boston MA USA Massachusetts General Hospital Center for Cancer Research Charlestown MA USA Dana-Farber Cancer Institute Boston MA USA Department of Biostatistics and Computational Biology Dana-Farber Cancer Institute and Harvard Medical School Boston MA USA Weill Cornell Medical College New York NY USA Department of Physiology and Biophysics Weill Cornell Medicine New York NY USA Institute for Computational Biomedicine Weill Cornell Medicine New York NY USA Controlled Department and Institution New York NY USA Englander Institute for Precision Medicine Weill Cornell Medicine Ne

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Modularity of the metabolic gene network as a prognostic biomarker for hepatocellular carcinoma

arXiv

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arXiv 2017年

作者： Ye, Fengdan Jia, Dongya Lu, Mingyang Levine, Herbert Deem, Michael W. Department of Physics & Astronomy Rice University HoustonTX77005 United States Center for Theoretical Biological Physics Rice University HoustonTX77005 United States Program in Systems Synthetic and Physical Biology Rice University HoustonTX77005 United States The Jackson Laboratory Bar HarborME04609 United States Department of Bioengineering Rice University HoustonTX77005 United States Department of Biosciences Rice University HoustonTX77005 United States

Abnormal metabolism is an emerging hallmark of cancer. Cancer cells utilize both aerobic glycolysis and oxidative phosphorylation (OXPHOS) for energy production and biomass synthesis. Understanding the metabolic reprogramming in cancer can help design therapies to target metabolism and thereby to improve prognosis. We have previously argued that more malignant tumors are usually characterized by a more modular expression pattern of cancer-associated genes. In this work, we analyzed the expression patterns of metabolism genes in terms of modularity for 371 hepatocellular carcinoma (HCC) samples from the Cancer Genome Atlas (TCGA). We found that higher modularity significantly correlated with glycolytic phenotype, later tumor stages, higher metastatic potential, and cancer recurrence, all of which contributed to poorer overall prognosis. Among patients that recurred, we found the correlation of greater modularity with worse prognosis during early to mid-progression. Furthermore, we developed metrics to calculate individual modularity, which was shown to be predictive of cancer recurrence and patients' survival and therefore may serve as a prognostic biomarker. Our overall conclusion is that more aggressive HCC tumors, as judged by decreased host survival probability, had more modular expression patterns of metabolic genes. These results may be used to identify cancer driver genes and for drug design. Copyright © 2017, The Authors. All rights reserved.

关键词： Metabolism

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Genomic basis for RNA alterations in cancer (vol 578, pg 129, 2020)

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NATURE 2023年第7948期614卷 E37-E37页

作者： Calabrese, Claudia Davidson, Natalie R. Demircioglu, Deniz Fonseca, Nuno A. He, Yao Lehmann, Kjong-Van Liu, Fenglin Shiraishi, Yuichi Soulette, Cameron M. Urban, Lara Greger, Liliana Li, Siliang Liu, Dongbing Perry, Marc D. Xiang, Qian Zhang, Fan Zhang, Junjun Bailey, Peter Erkek, Serap Hoadley, Katherine A. Hou, Yong Huska, Matthew R. Kilpinen, Helena Korbel, Jan O. Marin, Maximillian G. Markowski, Julia Nandi, Tannistha Pan-Hammarstrom, Qiang Pedamallu, Chandra Sekhar Siebert, Reiner Stark, Stefan G. Su, Hong Tan, Patrick Waszak, Sebastian M. Yung, Christina Zhu, Shida Awadalla, Philip Creighton, Chad J. Meyerson, Matthew Ouellette, B. F. Francis Wu, Kui Yang, Huanming Brazma, Alvis Brooks, Angela N. Goke, Jonathan Ratsch, Gunnar Schwarz, Roland F. Stegle, Oliver Zhang, Zemin European Molecular Biology Laboratory European Bioinformatics Institute Hinxton UK European Molecular Biology Laboratory European Bioinformatics Institute (EMBL-EBI) Cambridge UK Genome Biology Unit European Molecular Biology Laboratory (EMBL) Heidelberg Germany CIBIO/InBIO - Research Center in Biodiversity and Genetic Resources Universidade do Porto Vairão Portugal Berlin Institute for Medical Systems Biology Max Delbruck Center for Molecular Medicine Berlin Germany German Cancer Consortium (DKTK) partner site Berlin Germany German Cancer Research Center (DKFZ) Heidelberg Germany Berlin Institute for Medical Systems Biology Max Delbrück Center for Molecular Medicine Berlin Germany German Cancer Consortium (DKTK) Partner site Berlin Berlin Germany European Molecular Biology Laboratory Genome Biology Unit Heidelberg Germany Division of Computational Genomics and Systems Genetics German Cancer Research Center (DKFZ) Heidelberg Germany ETH Zurich Zurich Switzerland Memorial Sloan Kettering Cancer Center New York NY USA Weill Cornell Medical College New York NY USA SIB Swiss Institute of Bioinformatics Lausanne Switzerland University Hospital Zurich Zurich Switzerland Computational Biology Center Memorial Sloan Kettering Cancer Center New York NY USA Department of Biology ETH Zurich Zürich Switzerland Department of Computer Science ETH Zurich Zurich Switzerland Korea University Seoul South Korea Computational and Systems Biology Program Memorial Sloan Kettering Cancer Center New York NY USA Department of Physiology and Biophysics Weill Cornell Medicine New York NY USA Institute for Computational Biomedicine Weill Cornell Medicine New York NY USA Controlled Department and Institution New York NY USA Englander Institute for Precision Medicine Weill Cornell Medicine New York NY USA National University of Singapore Singapore Singapore Genome Institute of Singapore Singapore Singapore Computational and Systems Biology Genome Institute of Singap

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