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'Isotopo' a database application for facile analysis and management of mass isotopomer data

Database : the journal of biological databases and curation 2014年第2014期2014卷 1-8页

作者： Ahmed, Zeeshan Zeeshan, Saman Huber, Claudia Hensel, Michael Schomburg, Dietmar Münch, Richard Eylert, Eva Eisenreich, Wolfgang Dandekar, Thomas Department of Bioinformatics Biocenter University of Würzburg Am Hubland Department of Neurobiology and Genetics Biocenter University of Wuerzburg Am Hubland Institute of Molecular and Translational Therapeutic Strategies Hannover Medical School Lehrstuhl für Biochemie Center of Isotopologue Profiling Technische Universität München Division of Microbiology University of Osnabrück Department of Bioinformatics and Biochemistry Technical University Braunschweig Institute for Microbiology Biozentrum Technical University Braunschweig Germany and Computational biology and structures program European Molecular Biology Laboratory Germany Department of Bioinformatics Biocenter University of Würzburg Am Hubland Department of Neurobiology and Genetics Biocenter University of Wuerzburg Am Hubland Institute of Molecular and Translational Therapeutic Strategies Hannover Medical School Lehrstuhl für Biochemie Center of Isotopologue Profiling Technische Universität München Division of Microbiology University of Osnabrück Department of Bioinformatics and Biochemistry Technical University Braunschweig Institute for Microbiology Biozentrum Technical University Braunschweig Germany and Computational biology and structures program European Molecular Biology Laboratory 97074 Wuerzburg 97074 Wuerzburg Carl-Neuberg-Str. 1 Lichtenbergstraße 4 Barbarastraße 11 Gebäude 36 49076 Osnabrück Langer Kamp 19B 2. Obergeschoss Spielmannstraße 7 Meyerhofstr. 1 97074 Wuerzburg 97074 Wuerzburg Carl-Neuberg-Str. 1 Lichtenbergstraße 4 Barbarastraße 11 Gebäude 36 49076 Osnabrück Langer Kamp 19B 2. Obergeschoss Spielmannstraße 7 Braunschweig 38106 Hanover Germany Department of Bioinformatics Biocenter University of Würzburg Am Hubland Department of Neurobiology and Genetics Biocenter University of Wuerzburg Am Hubland Institute of Molecular and Translational Therapeutic Strategies Hannover Medical School Lehrstuhl für Biochemie Center of Isotopologue Profiling Technische Univer

UNLAbELLED: The composition of stable-isotope labelled isotopologues/isotopomers in metabolic products can be measured by mass spectrometry and supports the analysis of pathways and fluxes. As a prerequisite, the original mass spectra have to be processed, managed and stored to rapidly calculate, analyse and compare isotopomer enrichments to study, for instance, bacterial metabolism in infection. For such applications, we provide here the database application 'Isotopo'. This software package includes (i) a database to store and process isotopomer data, (ii) a parser to upload and translate different data formats for such data and (iii) an improved application to process and convert signal intensities from mass spectra of (13)C-labelled metabolites such as tertbutyldimethylsilyl-derivatives of amino acids. Relative mass intensities and isotopomer distributions are calculated applying a partial least square method with iterative refinement for high precision data. The data output includes formats such as graphs for overall enrichments in amino acids. The package is user-friendly for easy and robust data management of multiple experiments.;AVAILAbILITY: The 'Isotopo' software is available at the following web link (section Download): http://***/bioinformatics/isotopo/. The package contains three additional files: software executable setup (installer), one data set file (discussed in this article) and one excel file (which can be used to convert data from excel to '.iso' format). The 'Isotopo' software is compatible only with the Microsoft Windows operating system.;DATAbASE URL: http://***/bioinformatics/isotopo/. © The Author(s) 2014. Published by Oxford University Press.

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28 Gbshape: a genome browser database for DNA shape annotations

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Journal of biomolecular Structure and Dynamics 2015年第SUPP 1期33卷 16页

作者： Tsu-Pei Chiu[a][*] Lin Yang[a] Tianyin Zhou[a] bradley J. Main[a] Stephen C.J. Parker[b] Sergey V. Nuzhdin[a] Thomas D. Tullius[c] Remo Rohs[a] [a] Molecular and Computational Biology Program Department of Biological Sciences University of Southern California Los Angeles CA 90089 USA[b] Departments of Computational Medicine and Bioinformatics and Human Genetics University of Michigan Ann Arbor MI 48109 USA[c] Department of Chemistry and Program in Bioinformatics Boston University Boston MA 02215 USA

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71 Genomic regions flanking E-box binding sites influence DNA binding specificity of bHLH transcription factors through DNA shape

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Journal of biomolecular Structure and Dynamics 2013年第SUPP 1期31卷 45-46页

作者： Raluca Gordan[a][b][*] Ning Shen[c] Iris Dror[d] Tianyin Zhou[d] John Horton[b] Remo Rohs[d] & Martha L. bulyk[e][f] [a] Departments of Biostatistics and Bioinformatics Computer Science and Molecular Genetics and Microbiology Duke University Durham NC USA [b] Institute for Genome Sciences and Policy Duke University Durham NC 27708 USA Phone: Phone: +1 (919) 667-8673 Fax: Phone: +1 (919) 667-8673 [c] Department of Pharmacology and Cancer Biology Duke University Durham NC 27708 USA [d] Molecular and Computational Biology Program Departments of Biological Sciences Chemistry and Physics and Astronomy University of Southern California 1050 Childs Way Los Angeles CA 90089 USA [e] Division of Genetics Departments of Medicine and Pathology Brigham and Women’s Hospital and Harvard Medical School Boston MA 02115 USA [f] Harvard-MIT Division of Health Sciences and Technology (HST) Harvard Medical School Boston MA 02115 USA

Transcriptional regulation of gene expression is enacted mainly through binding of transcription factors (TFs) to specific, short DNA sites in cis-regulatory regions of genes. Most TFs are members of protein families that share a common DNA-binding domain and thus recognize similar DNA-binding sequences. It is not well understood why paralogous TFs often bind different genomic target sitesin vivoto effect different regulatory programs, despite apparently recognizing the same sequence motifs. Here, we designed custom protein-binding microarrays (PbMs) to analyze the DNA-binding specificities of twoSaccharomyces cerevisiaebasic helix-loop-helix (bHLH) proteins, Tye7 and Cbf1, as a model system. Our data reveal that E-box DNA-binding sequences (CAnnTG), when tested in the context of their native genomic flanking sequences, are bound differently by Cbf1 and Tye7. computational models of the PbM data indicate that DNA sequence features located in the genomic sequences outside the E-box contribute to DNA-binding specificityin vitro. Our analyses suggest that these flanking regions affect DNA-binding specificity indirectly by influencing the three-dimensional structure of the E-box binding sites. Finally, we show that these subtle differences in intrinsic sequence preferences of Cbf1 and Tye7in vitrohelp to explain their differential DNA-binding preferencesin vivo. Our results provide further evidence that the local shape of DNA-binding sites may be an important feature in distinguishing the DNA-binding preferences among paralogous TFs and thus may play a widespread role in determining how transcriptional regulatory specificity within TF families is achieved.

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103 Probing DNA shape and methylation state on a genomic scale with DNase I

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Journal of biomolecular Structure and Dynamics 2013年第SUPP 1期31卷 65页

作者： Allan Lazarovici[a][b] Tianyin Zhou[c] Anthony Shafer[d] Ana Carolina Dantas Machado[c] Richard Sandstrom[d] Peter J. Sabo[d] Yan Lu[c] Remo Rohs[c] John A. Stamatoyannopoulos[d] & Harmen J. bussemaker[b][e][*] [a] Department of Electrical Engineering Columbia University New York NY 10027 USA [b] Department of Biological Sciences Columbia University New York NY 10027 USA [c] Molecular and Computational Biology Program Departments of Biological Sciences Chemistry and Physics and Astronomy University of Southern California Los Angeles CA 90089 USA [d] Departments of Genome Sciences and Medicine University of Washington Seattle WA 98195 USA [e] Center for Computational Biology and Bioinformatics Columbia University New York NY 10032 USA Phone: Phone: (212) 854-9932 Fax: Phone: (212) 854-9932

DNA binding proteins find their cognate sequences within genomic DNA through recognition of specific chemical and structural features. Here, we demonstrate that high-resolution DNase I cleavage profiles can provide detailed information about the shape and chemical modification status of genomic DNA. Analyzing millions of DNA-backbone hydrolysis events on naked genomic DNA, we show that the intrinsic rate of cleavage by DNase I closely tracks the width of the minor groove. Integration of these DNase I cleavage data with bisulfite sequencing data for the same cell type genome reveals that the cleavage directly adjacent to CpG dinucleotides is enhanced at least eight-fold by cytosine methylation. This phenomenon we show is attributable to methylation-induced narrowing of the minor groove. Furthermore, we demonstrate that it enables simultaneous mapping of DNase I hypersensitivity and regional DNA methylation levels using densein vivocleavage data. Taken together, our results suggest a general mechanism through which CpG methylation can modulate protein–DNA interaction strength via the remodeling of DNA shape.

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Weight, habitual fibre intake, and microbiome composition predict tolerance to fructan supplementation

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Journal of Plant Foods 2024年第6期75卷

作者： Jeffrey Letourneau benjamin C. Neubert Diana Dayal Verónica M. Carrion Heather K. Durand Eric P. Dallow Sharon Jiang Michelle Kirtley Geoffrey S. Ginsburg P. Murali Doraiswamy Lawrence A. David a Department of Molecular Genetics and Microbiology Duke University School of Medicine Durham NC USA b Program in Computational Biology and Bioinformatics Duke University School of Medicine Durham NC USA c School of Medicine University of North Carolina Chapel Hill NC USA d Duke Office of Clinical Research Duke University Durham NC USA e Duke Center for Applied Genomics and Precision Medicine Duke University Health System Durham NC USAf Department of Medicine Duke University School of Medicine Durham NC USA e Duke Center for Applied Genomics and Precision Medicine Duke University Health System Durham NC USAf Department of Medicine Duke University School of Medicine Durham NC USAg Department of Psychiatry Duke University School of Medicine Durham NC USAh Duke Microbiome Center Duke University School of Medicine Durham NC USA a Department of Molecular Genetics and Microbiology Duke University School of Medicine Durham NC USAb Program in Computational Biology and Bioinformatics Duke University School of Medicine Durham NC USAh Duke Microbiome Center Duke University School of Medicine Durham NC USA

Fructans are commonly used as dietary fibre supplements for their ability to promote the growth of beneficial gut microbes. However, fructan consumption has been associated with various dosage-dependent side effects. We characterised side effects in an exploratory analysis of a randomised trial in healthy adults (n= 40) who consumed 18 g/day inulin or placebo. We found that individuals weighing more or habitually consuming higher fibre exhibited the best tolerance. Furthermore, we identified associations between gut microbiome composition and host tolerance. Specifically, higher levels ofChristensenellaceae R-7 groupwere associated with gastrointestinal discomfort, and a machine-learning-based approach successfully predicted high levels of flatulence, with[Ruminococcus] torques groupand (Oscillospiraceae)UCG-002 *** as key predictive taxa. These data reveal trends that can help guide personalised recommendations for initial inulin dosage. Our results support prior ecological findings indicating that fibre supplementation has the greatest impact on individuals whose baseline fibre intake is lowest.

关键词： Microbiome inulin dietary fibre gastroenterology bioinformatics

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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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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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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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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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The evolutionary history of 2,658 cancers (vol 578, pg 122, 2020)

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NATURE 2023年第7948期614卷 E42-E42页

作者： Gerstung, Moritz Jolly, Clemency Leshchiner, Ignaty Dentro, Stefan C. Gonzalez, Santiago Rosebrock, Daniel Mitchell, Thomas J. Rubanova, Yulia Anur, Pavana Yu, Kaixian Tarabichi, Maxime Deshwar, Amit Wintersinger, Jeff Kleinheinz, Kortine Vazquez-Garcia, Ignacio Haase, Kerstin Jerman, Lara Sengupta, Subhajit Macintyre, Geoff Malikic, Salem Donmez, Nilgun Livitz, Dimitri G. Cmero, Marek Demeulemeester, Jonas Schumacher, Steven Fan, Yu Yao, Xiaotong Lee, Juhee Schlesner, Matthias boutros, Paul C. bowtell, David D. Zhu, Hongtu Getz, Gad Imielinski, Marcin beroukhim, Rameen Sahinalp, S. Cenk Ji, Yuan Peifer, Martin Markowetz, Florian Mustonen, Ville Yuan, Ke Wang, Wenyi Morris, Quaid D. Spellman, Paul T. Wedge, David C. Van Loo, Peter European Molecular Biology Laboratory European Bioinformatics Institute (EMBL-EBI) Cambridge UK European Molecular Biology Laboratory Genome Biology Unit Heidelberg Germany Wellcome Sanger Institute Cambridge UK Genome Biology Unit European Molecular Biology Laboratory (EMBL) Heidelberg Germany University of Ljubljana Ljubljana Slovenia The Francis Crick Institute London UK Big Data Institute University of Oxford Oxford UK Wellcome Sanger Institute Wellcome Genome Campus Hinxton UK Big Data Institute Li Ka Shing Centre University of Oxford Oxford UK University of Cambridge Cambridge UK Cambridge University Hospitals NHS Foundation Trust Cambridge UK Department of Applied Mathematics and Theoretical Physics Centre for Mathematical Sciences University of Cambridge Cambridge UK Department of Epidemiology and Biostatistics Memorial Sloan Kettering Cancer Center New York NY USA Department of Statistics Columbia University New York NY USA Department of Haematology University of Cambridge Cambridge UK University of Leuven Leuven Belgium Broad Institute of MIT and Harvard Cambridge MA USA Center for Cancer Research Massachusetts General Hospital Charlestown MA USA Department of Pathology Massachusetts General Hospital Boston MA USA Harvard Medical School Boston MA USA Center for Cancer Research Massachusetts General Hospital Boston MA USA Dana-Farber Cancer Institute Boston MA USA Department of Medical Oncology Dana-Farber Cancer Institute Boston MA USA Department of Cancer Biology Dana-Farber Cancer Institute Boston MA USA Oxford NIHR Biomedical Research Centre Oxford UK Oxford NIHR Biomedical Research Centre University of Oxford Oxford UK University of Toronto Toronto Ontario Canada Vector Institute Toronto Ontario Canada Vector Institute Toronto ON Canada Department of Computer Science University of Toronto Toronto ON Canada Ontario Institute for Cancer Research Toronto Ontario Canada University of California Los Angeles

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