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Author Correction: The power of genetic diversity in genome-wide association studies of lipids

Nature 2023年第7965期618卷 E19-E20页

作者： Sarah E Graham Shoa L Clarke Kuan-Han H Wu Stavroula Kanoni Greg J M Zajac Shweta Ramdas Ida Surakka Ioanna Ntalla Sailaja Vedantam Thomas W Winkler Adam E Locke Eirini Marouli Mi Yeong Hwang Sohee Han Akira Narita Ananyo Choudhury Amy R Bentley Kenneth Ekoru Anurag Verma Bhavi Trivedi Hilary C Martin Karen A Hunt Qin Hui Derek Klarin Xiang Zhu Gudmar Thorleifsson Anna Helgadottir Daniel F Gudbjartsson Hilma Holm Isleifur Olafsson Masato Akiyama Saori Sakaue Chikashi Terao Masahiro Kanai Wei Zhou Ben M Brumpton Humaira Rasheed Sanni E Ruotsalainen Aki S Havulinna Yogasudha Veturi QiPing Feng Elisabeth A Rosenthal Todd Lingren Jennifer Allen Pacheco Sarah A Pendergrass Jeffrey Haessler Franco Giulianini Yuki Bradford Jason E Miller Archie Campbell Kuang Lin Iona Y Millwood George Hindy Asif Rasheed Jessica D Faul Wei Zhao David R Weir Constance Turman Hongyan Huang Mariaelisa Graff Anubha Mahajan Michael R Brown Weihua Zhang Ketian Yu Ellen M Schmidt Anita Pandit Stefan Gustafsson Xianyong Yin Jian'an Luan Jing-Hua Zhao Fumihiko Matsuda Hye-Mi Jang Kyungheon Yoon Carolina Medina-Gomez Achilleas Pitsillides Jouke Jan Hottenga Gonneke Willemsen Andrew R Wood Yingji Ji Zishan Gao Simon Haworth Ruth E Mitchell Jin Fang Chai Mette Aadahl Jie Yao Ani Manichaikul Helen R Warren Julia Ramirez Jette Bork-Jensen Line L Kårhus Anuj Goel Maria Sabater-Lleal Raymond Noordam Carlo Sidore Edoardo Fiorillo Aaron F McDaid Pedro Marques-Vidal Matthias Wielscher Stella Trompet Naveed Sattar Line T Møllehave Betina H Thuesen Matthias Munz Lingyao Zeng Jianfeng Huang Bin Yang Alaitz Poveda Azra Kurbasic Claudia Lamina Lukas Forer Markus Scholz Tessel E Galesloot Jonathan P Bradfield E Warwick Daw Joseph M Zmuda Jonathan S Mitchell Christian Fuchsberger Henry Christensen Jennifer A Brody Mary F Feitosa Mary K Wojczynski Michael Preuss Massimo Mangino Paraskevi Christofidou Niek Verweij Jan W Benjamins Jorgen Engmann Rachel L Kember Roderick C Slieker Ken Sin Lo Nuno R Zilhao Phuong Le Marcus E Kleber Graciela E Delgado Shaofeng Huo Dai Department of Internal Medicine Division of Cardiology University of Michigan Ann Arbor MI USA. VA Palo Alto Health Care System Palo Alto CA USA. Department of Medicine Division of Cardiovascular Medicine Stanford University School of Medicine Stanford CA USA. Department of Computational Medicine and Bioinformatics University of Michigan Ann Arbor MI USA. William Harvey Research Institute Barts and the London School of Medicine and Dentistry Queen Mary University of London London UK. Department of Biostatistics and Center for Statistics Genetics University of Michigan Ann Arbor MI USA. Department of Genetics Perelman School of Medicine University of Pennsylvania Philadelphia PA USA. Clinical Pharmacology William Harvey Research Institute Barts and The London School of Medicine and Dentistry Queen Mary University of London London UK. Endocrinology Boston Children's Hospital Boston MA USA. Medical and Population Genetics Broad Institute Cambridge MA USA. Department of Genetic Epidemiology University of Regensburg Regensburg Germany. McDonnell Genome Institute and Department of Medicine Washington University St Louis MO USA. Department of Precision Medicine Division of Genome Science National Institute of Health Cheongju-si South Korea. Tohoku Medical Megabank Organization Tohoku University Sendai Japan. Sydney Brenner Institute for Molecular Bioscience Faculty of Health Sciences University of the Witwatersrand Johannesburg South Africa. Center for Research on Genomics and Global Health National Human Genome Research Institute National Institutes of Health Bethesda MD USA. Blizard Institute Barts and the London School of Medicine and Dentistry Queen Mary University of London London UK. Wellcome Sanger Institute Hinxton UK. Department of Epidemiology Emory University Rollins School of Public Health Atlanta GA USA. Atlanta VA Health Care System Decatur GA USA. Malcolm Randall VA Medical Center Gainesville FL USA. Division of Vascular Sur

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Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population

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Nature communications 2023年第1期14卷 3043页

作者： Jianxin Shi Kouya Shiraishi Jiyeon Choi Keitaro Matsuo Tzu-Yu Chen Juncheng Dai Rayjean J Hung Kexin Chen Xiao-Ou Shu Young Tae Kim Maria Teresa Landi Dongxin Lin Wei Zheng Zhihua Yin Baosen Zhou Bao Song Jiucun Wang Wei Jie Seow Lei Song I-Shou Chang Wei Hu Li-Hsin Chien Qiuyin Cai Yun-Chul Hong Hee Nam Kim Yi-Long Wu Maria Pik Wong Brian Douglas Richardson Karen M Funderburk Shilan Li Tongwu Zhang Charles Breeze Zhaoming Wang Batel Blechter Bryan A Bassig Jin Hee Kim Demetrius Albanes Jason Y Y Wong Min-Ho Shin Lap Ping Chung Yang Yang She-Juan An Hong Zheng Yasushi Yatabe Xu-Chao Zhang Young-Chul Kim Neil E Caporaso Jiang Chang James Chung Man Ho Michiaki Kubo Yataro Daigo Minsun Song Yukihide Momozawa Yoichiro Kamatani Masashi Kobayashi Kenichi Okubo Takayuki Honda Dean H Hosgood Hideo Kunitoh Harsh Patel Shun-Ichi Watanabe Yohei Miyagi Haruhiko Nakayama Shingo Matsumoto Hidehito Horinouchi Masahiro Tsuboi Ryuji Hamamoto Koichi Goto Yuichiro Ohe Atsushi Takahashi Akiteru Goto Yoshihiro Minamiya Megumi Hara Yuichiro Nishida Kenji Takeuchi Kenji Wakai Koichi Matsuda Yoshinori Murakami Kimihiro Shimizu Hiroyuki Suzuki Motonobu Saito Yoichi Ohtaki Kazumi Tanaka Tangchun Wu Fusheng Wei Hongji Dai Mitchell J Machiela Jian Su Yeul Hong Kim In-Jae Oh Victor Ho Fun Lee Gee-Chen Chang Ying-Huang Tsai Kuan-Yu Chen Ming-Shyan Huang Wu-Chou Su Yuh-Min Chen Adeline Seow Jae Yong Park Sun-Seog Kweon Kun-Chieh Chen Yu-Tang Gao Biyun Qian Chen Wu Daru Lu Jianjun Liu Ann G Schwartz Richard Houlston Margaret R Spitz Ivan P Gorlov Xifeng Wu Ping Yang Stephen Lam Adonina Tardon Chu Chen Stig E Bojesen Mattias Johansson Angela Risch Heike Bickeböller Bu-Tian Ji H-Erich Wichmann David C Christiani Gadi Rennert Susanne Arnold Paul Brennan James McKay John K Field Sanjay S Shete Loic Le Marchand Geoffrey Liu Angeline Andrew Lambertus A Kiemeney Shan Zienolddiny-Narui Kjell Grankvist Mikael Johansson Angela Cox Fiona Taylor Jian-Min Yuan Philip Lazarus Matthew B Schabath Melinda C Aldrich Hyo-Sung Jeon Shih Sheng Jiang Jae Sook Sung C Division of Cancer Epidemiology and Genetics National Cancer Institute Rockville MD USA. jianxin.shi@nih.gov. Division of Genome Biology National Cancer Research Institute Tokyo Japan. Division of Cancer Epidemiology and Genetics National Cancer Institute Rockville MD USA. Division of Cancer Epidemiology and Prevention Aichi Cancer Center Research Institute Nagoya Japan. Institute of Population Health Sciences National Health Research Institutes Zhunan Taiwan. Department of Epidemiology School of Public Health Nanjing Medical University Nanjing China. Jiangsu Key Lab of Cancer Biomarkers Prevention and Treatment Collaborative Innovation Center for Cancer Medicine Nanjing Medical University Nanjing China. Prosserman Centre for Population Health Research Lunenfeld-Tanenbaum Research Institute Sinai Health Toronto ON Canada. Department of Epidemiology and Biostatistics National Clinical Research Center for Cancer Key Laboratory of Molecular Cancer Epidemiology of Tianjin Tianjin Medical University Cancer Institute and Hospital Tianjin Medical University Tianjin China. Division of Epidemiology Department of Medicine Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center Nashville TN USA. Cancer Research Institute Seoul National University College of Medicine Seoul Republic of Korea. Department of Etiology & Carcinogenesis and State Key Laboratory of Molecular Oncology Cancer Institute and Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China. Department of Epidemiology School of Public Health China Medical University Shenyang China. Department of Clinical Epidemiology and Center of Evidence Based Medicine The First Hospital of China Medical University Shenyang China. Department of Oncology Shandong Cancer Hospital and Institute Shandong Academy of Medical Sciences Jinan China. Ministry of Education Key Laboratory of Contemporary Anthropology School of Life Sciences Fudan University Shanghai China. S

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (P = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications.

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Front Cover: Synthesis and Immunomodulatory Activity of Fluorine-Containing Bisphosphonates (ChemMedChem 4/2019)

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ChemMedChem 2019年第4期14卷 360-360页

作者： Dr. Satoshi Mizuta Mohammed S. O. Tagod Dr. Masashi Iwasaki Prof. Yoichi Nakamura Dr. Hiroaki Senju Prof. Hiroshi Mukae Prof. Craig T. Morita Prof. Yoshimasa Tanaka Center for Bioinformatics and Molecular Medicine Graduate School of Biomedical Sciences Nagasaki University 1-12-4 Sakamoto Nagasaki 852-8523 Japan Program for Nurturing Global Leaders in Tropical and Emerging Infectious Diseases Graduate School of Biomedical Sciences Nagasaki University 1-12-4 Sakamoto Nagasaki 852-8523 Japan Center for Innovation in Immunoregulative Technology and Therapeutics Graduate School of Medicine Kyoto University Yoshidakonoe-cho Kyoto 606-8501 Japan Department of Respiratory Medicine Nagasaki University School of Medicine 1-7-1 Sakamoto Nagasaki 852-8501 Japan Department of Internal Medicine and the Interdisciplinary Graduate Program in Immunology University of Iowa Carver College of Medicine Iowa City Veterans Affairs Health Care System Iowa City IA 52246 USA Hyogo College of Medicine 1-1 Mukogawa Nishinomiya Hyogo 663-8501 Japan

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AKT3-mediated IWS1 phosphorylation promotes the proliferation of EGFR-mutant lung adenocarcinomas through cell cycle-regulated U2AF2 RNA splicing

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Nature communications 2021年第1期12卷 4624页

作者： Georgios I Laliotis Evangelia Chavdoula Maria D Paraskevopoulou Abdul Kaba Alessandro La Ferlita Satishkumar Singh Vollter Anastas Keith A Nair Arturo Orlacchio Vasiliki Taraslia Ioannis Vlachos Marina Capece Artemis Hatzigeorgiou Dario Palmieri Christos Tsatsanis Salvatore Alaimo Lalit Sehgal David P Carbone Vincenzo Coppola Philip N Tsichlis Department of Cancer Biology and Genetics The Ohio State University Columbus OH USA. glaliot1@jhmi.edu. The Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute Columbus OH USA. glaliot1@jhmi.edu. School of Medicine University of Crete Heraklion Crete Greece. glaliot1@jhmi.edu. Department of Oncology Sidney Kimmel Comprehensive Cancer Center Johns Hopkins School of Medicine Baltimore MD USA. glaliot1@jhmi.edu. Department of Cancer Biology and Genetics The Ohio State University Columbus OH USA. The Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute Columbus OH USA. Molecular Oncology Research Institute Tufts Medical Center Boston MA USA. Department of Clinical and Experimental Medicine Bioinformatics Unit University of Catania Catania Italy. Department of Medicine Division of Hematology The Ohio State University Columbus OH USA. Tufts Graduate School of Biomedical Sciences Program in Genetics Boston MA USA. Center of Basic Research Biomedical Research Foundation of the Academy of Athens Athens Greece. DIANA-Lab Hellenic Pasteur Institute Athens Greece. Department Of Pathology Beth Israel-Deaconess Medical Center Harvard Medical School Boston MA USA. School of Medicine University of Crete Heraklion Crete Greece. Institute of Molecular Biology and Biotechnology Foundation for Research and Technology Hellas Heraklion Crete Greece. Department of Internal Medicine Division of Medical Oncology The Ohio State University Medical Center Columbus OH USA. Department of Cancer Biology and Genetics The Ohio State University Columbus OH USA. Philip.tsichlis@osumc.edu. The Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute Columbus OH USA. Philip.tsichlis@osumc.edu. Tufts Graduate School of Biomedical Sciences Program in Genetics Boston MA USA.

AKT-phosphorylated IWS1 regulates alternative RNA splicing via a pathway that is active in lung cancer. RNA-seq studies in lung adenocarcinoma cells lacking phosphorylated IWS1, identified a exon 2-deficient U2AF2 splice variant. Here, we show that exon 2 inclusion in the U2AF2 mRNA is a cell cycle-dependent process that is regulated by LEDGF/SRSF1 splicing complexes, whose assembly is controlled by the IWS1 phosphorylation-dependent deposition of histone H3K36me3 marks in the body of target genes. The exon 2-deficient U2AF2 mRNA encodes a Serine-Arginine-Rich (RS) domain-deficient U2AF65, which is defective in CDCA5 pre-mRNA processing. This results in downregulation of the CDCA5-encoded protein Sororin, a phosphorylation target and regulator of ERK, G2/M arrest and impaired cell proliferation and tumor growth. Analysis of human lung adenocarcinomas, confirmed activation of the pathway in EGFR-mutant tumors and showed that pathway activity correlates with tumor stage, histologic grade, metastasis, relapse after treatment, and poor prognosis.

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Author Correction: Effect of de novo transcriptome assembly on transcript quantification

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Scientific reports 2019年第1期9卷 18041页

作者： Ping-Han Hsieh Yen-Jen Oyang Chien-Yu Chen Graduate Institute of Biomedical Electronics and Bioinformatics National Taiwan University Taipei 10617 Taiwan. Department of Computer Science and Information Engineering National Taiwan University Taipei 10617 Taiwan. Department of Bio-Industrial Mechatronics Engineering National Taiwan University Taipei 10617 Taiwan. chienyuchen@ntu.edu.tw. Genome and Systems Biology Program National Taiwan University and Academia sinica Taipei 10617 Taiwan. chienyuchen@ntu.edu.tw.

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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Genetic load makes cancer cells more sensitive to common drugs: Evidence from Cancer Cell Line Encyclopedia

arXiv

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arXiv 2017年

作者： Pavel, Ana B. Korolev, Kirill S. Graduate Program in Bioinformatics Boston University 44 Cummington Mall BostonMA02215 United States Department of Physics Boston University 590 Commonwealth Avenue BostonMA02215 United States

Genetic alterations initiate tumors and enable the evolution of drug resistance. The pro-cancer view of mutations is however incomplete, and several studies show that mutational load can reduce tumor fitness. Given its negative effect, genetic load should make tumors more sensitive to anticancer drugs. Here, we test this hypothesis across all major types of cancer from the Cancer Cell Line Encyclopedia, that provides genetic and expression data of 496 cell lines together with their response to 24 common anticancer drugs. We found that the efficacy of 9 out of 24 drugs showed significant association with genetic load in a pan-cancer analysis. The associations for some tissue-drug combinations were remarkably strong with genetic load explaining up to 83% of the variance in the drug response. Overall, the role of genetic load depended on both the drug and the tissue type with 10 tissues being particularly vulnerable to genetic load. We also identified changes in gene expression associated with increased genetic load, which included cell-cycle checkpoints, DNA damage and apoptosis. Our results show that genetic load is an important component of tumor fitness and can predict drug sensitivity. Beyond being a biomarker, genetic load might be a new, unexplored vulnerability of cancer. Copyright © 2017, The Authors. All rights reserved.

关键词： Tumors

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FungalTraits:a user-friendly traits database of fungi and fungus-like stramenopiles

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Fungal Diversity 2020年第6期105卷 I0001-I0016页

作者： Sergei Põlme Kessy Abarenkov RHenrik Nilsson Björn D.Lindahl Karina Engelbrecht Clemmensen Havard Kauserud Nhu Nguyen Rasmus Kjøller Scott T.Bates Petr Baldrian Tobias Guldberg Frøslev Kristjan Adojaan Alfredo Vizzini Ave Suija Donald Pfister Hans-Otto Baral Helle Järv Hugo Madrid Jenni Nordén Jian-Kui Liu Julia Pawlowska Kadri Põldmaa Kadri Pärtel Kadri Runnel Karen Hansen Karl-Henrik Larsson Kevin David Hyde Marcelo Sandoval-Denis Matthew E.Smith Merje Toome-Heller Nalin N.Wijayawardene Nelson Menolli Jr Nicole K.Reynolds Rein Drenkhan Sajeewa S.N.Maharachchikumbura Tatiana B.Gibertoni Thomas Læssøe William Davis Yuri Tokarev Adriana Corrales Adriene Mayra Soares Ahto Agan Alexandre Reis Machado Andrés Argüelles-Moyao Andrew Detheridge Angelina de Meiras-Ottoni Annemieke Verbeken Arun Kumar Dutta Bao-Kai Cui C.K.Pradeep César Marín Daniel Stanton Daniyal Gohar Dhanushka N.Wanasinghe Eveli Otsing Farzad Aslani Gareth W.Griffith Thorsten H.Lumbsch Hans-Peter Grossart Hossein Masigol Ina Timling Inga Hiiesalu Jane Oja John Y.Kupagme József Geml Julieta Alvarez-Manjarrez Kai Ilves Kaire Loit Kalev Adamson Kazuhide Nara Kati Küngas Keilor Rojas-Jimenez Krišs Bitenieks Laszlo Irinyi LászlóGNagy Liina Soonvald Li-Wei Zhou Lysett Wagner M.Catherine Aime MaarjaÖpik María Isabel Mujica Martin Metsoja Martin Ryberg Martti Vasar Masao Murata Matthew PNelsen Michelle Cleary Milan C.Samarakoon Mingkwan Doilom Mohammad Bahram Niloufar Hagh-Doust Olesya Dulya Peter Johnston Petr Kohout Qian Chen Qing Tian Rajasree Nandi Rasekh Amiri Rekhani Hansika Perera Renata dos Santos Chikowski Renato L.Mendes-Alvarenga Roberto Garibay-Orijel Robin Gielen Rungtiwa Phookamsak Ruvishika S.Jayawardena Saleh Rahimlou Samantha C.Karunarathna Saowaluck Tibpromma Shawn P.Brown Siim-Kaarel Sepp Sunil Mundra Zhu-Hua Luo Tanay Bose Tanel Vahter Tarquin Netherway Teng Yang Tom May Torda Varga Wei Li Victor Rafael Matos Coimbra Virton Rodrigo Targino de Oliveira Vitor Xavier de Lima Vladimir S.Mikryukov Yongzhong Lu Yosuke Matsuda Yumiko Miyamoto Urm Institute of Ecology and Earth Sciences University of Tartu14A Ravila50411 TartuEstonia Natural History Museum University of Tartu46 Vanemuise Str51003 TartuEstonia Gothenburg Global Biodiversity Centre Box 46140530 GothenburgSweden Department of Biological and Environmental Sciences University of GothenburgGothenburgSweden Department of Soil and Environment Swedish University of Agricultural SciencesBox 701475007 UppsalaSweden Department of Forest Mycology and Plant Pathology Swedish University of Agricultural SciencesBox 702675007 UppsalaSweden Section for Genetics and Evolutionary Biology(EvoGene) Department of BiosciencesUniversity of OsloP.O.Box 1066BlindernNO-0316 OsloNorway University of Hawaiʻi at Mānoa 3190 Maile WaySt.John 102HonoluluHIUSA Department of Biology University of CopenhagenUniversitetsparken 152100 CopenhagenØDenmark Purdue University Northwest WestvilleIN 46391USA Institute of Microbiology Czech Academy of SciencesVidenska 108314220 Praha 4Czech Republic GLOBE Institute University of CopenhagenØster Farimagsgade 5KH7.2.321353 CopenhagenDenmark Dipartimento di Scienze della Vita e Biologia dei Sistemi Universitàdi TorinoViale Mattioli 2510125 TorinoItaly Department of Organismic and Evolutionary Biology and Farlow Library and Herbarium Harvard University22 Divinity AveCambridgeMA 02138USA Blaihofstr.42 72074 TübingenGermany SYNLAB Estonia Veerenni 53aTallinn 11313Estonia Escuela de Tecnología Médica Universidad Santo TomásLos Carreras 753OsornoChile Centro de Genómica y Bioinformática Universidad MayorCamino La Pirámide 5750HuechurabaSantiagoChile Norwegian Institute for Nature Research(NINA) Sognsveien 680855 OsloNorway School of Life Science and Technology University of Electronic Science and Technology of ChinaChengdu 611731People’s Republic of China Evolutionary Biology Faculty of BiologyBiological and Chemical Research CentreUniversity of Warsawul.Zwirki i Wigury 10102-089 WarsawPoland Department of Botany Swedish Museum of

The cryptic lifestyle of most fungi necessitates molecular identification of the guild in environmental *** the past decades,rapid development and affordability of molecular tools have tremendously improved insights of the fungal diversity in all ecosystems and ***,in spite of the progress of molecular methods,knowledge about functional properties of the fungal taxa is vague and interpretation of environmental studies in an ecologically meaningful manner remains *** order to facilitate functional assignments and ecological interpretation of environmental studies we introduce a user friendly traits and character database FungalTraits operating at genus and species hypothesis *** the information from previous efforts such as FUNGuild and FunFun together with involvement of expert knowledge,we reannotated 10,210 and 151 fungal and Stramenopila genera,*** resulted in a stand-alone spreadsheet dataset covering 17 lifestyle related traits of fungal and Stramenopila genera,designed for rapid functional assignments of environmental *** order to assign the trait states to fungal species hypotheses,the scientific community of experts manually categorised and assigned available trait information to 697,413 fungal ITS *** the basis of those sequences we were able to summarise trait and host information into 92,623 fungal species hypotheses at 1%dissimilarity threshold.

关键词： Fungal traits Trophic modes Function Guild bioinformatics High-throughput sequencing Community ecology

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Genome-wide association studies identify susceptibility loci for epithelial ovarian cancer in east Asian women

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Gynecologic oncology 2019年第2期153卷 343-355页

作者： Kate Lawrenson Fengju Song Dennis J Hazelett Siddhartha P Kar Jonathan Tyrer Catherine M Phelan Rosario I Corona Norma I Rodríguez-Malavé Ji-Hei Seo Emily Adler Simon G Coetzee Felipe Segato Marcos A S Fonseca Christopher I Amos Michael E Carney Georgia Chenevix-Trench Jiyeob Choi Jennifer A Doherty Weihua Jia Gang J Jin Byoung-Gie Kim Nhu D Le Juyeon Lee Lian Li Boon K Lim Noor A Adenan Mika Mizuno Boyoung Park Celeste L Pearce Kang Shan Yongyong Shi Xiao-Ou Shu Weiva Sieh Pamela J Thompson Lynne R Wilkens Qingyi Wei Yin L Woo Li Yan Beth Y Karlan Matthew L Freedman Houtan Noushmehr Ellen L Goode Andrew Berchuck Thomas A Sellers Soo-Hwang Teo Wei Zheng Keitaro Matsuo Sue Park Kexin Chen Paul D P Pharoah Simon A Gayther Marc T Goodman Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute Cedars-Sinai Medical Center 8700 Beverly Boulevard Suite 290W Los Angeles CA USA Center for Bioinformatics and Functional Genomics Cedars Sinai Genomics Core Cedars-Sinai Medical Center Los Angeles CA USA. Electronic address: kate.lawrenson@***. National Clinical Research Center for Cancer Tianjin Medical University Cancer Institute and Hospital Tianjin China Department of Epidemiology and Biostatistics Key Laboratory of Cancer Prevention and Therapy Tianjin China. Center for Bioinformatics and Functional Genomics Cedars Sinai Genomics Core Cedars-Sinai Medical Center Los Angeles CA USA. Department of Oncology Centre for Cancer Genetic Epidemiology University of Cambridge Strangeways Research Laboratory Cambridge UK. Department of Gynecologic Oncology Moffitt Cancer Center Tampa FL USA Department of Cancer Epidemiology Moffitt Cancer Center Tampa FL USA. Center for Bioinformatics and Functional Genomics Cedars Sinai Genomics Core Cedars-Sinai Medical Center Los Angeles CA USA. Department of Medical Oncology Dana-Farber Cancer Institute Boston MA USA. Department of Preventive Medicine University of Southern California Keck School of Medicine 1450 Biggy Street Los Angeles CA USA. Department of Genetics Ribeirão Preto Medical School University of São Paulo 14049-900 Brazil. Institute for Clinical and Translational Research Department of Medicine Baylor School of Medicine HoustonTX USA. Department of Obstetrics and Gynecology John A. Burns School of Medicine University of Hawaii Honolulu HI USA. Genetics and Computational Biology Department QIMR Berghofer Medical Research Institute 300 Herston Road Herston QLD 4006 Australia. Department of Preventive Medicine Seoul National University College of Medicine Seoul Republic of Korea Cancer Research Institute Seoul National University Seoul Republic of Korea Department of Biomedical Science Graduate School Seoul National Un

OBJECTIVE:Genome-wide association studies (GWASs) for epithelial ovarian cancer (EOC) have focused largely on populations of European ancestry. We aimed to identify common germline variants associated with EOC risk in Asian women. METHODS:Genotyping was performed as part of the OncoArray project. Samples with >60% Asian ancestry were included in the analysis. Genotyping was performed on 533,631 SNPs in 3238 Asian subjects diagnosed with invasive or borderline EOC and 4083 unaffected controls. After imputation, genotypes were available for 11,595,112 SNPs to identify associations. RESULTS:At chromosome 6p25.2, SNP rs7748275 was associated with risk of serous EOC (odds ratio [OR] = 1.34, P = 8.7 × 10) and high-grade serous EOC (HGSOC) (OR = 1.34, P = 4.3 × 10). SNP rs6902488 at 6p25.2 (r = 0.97 with rs7748275) lies in an active enhancer and is predicted to impact binding of STAT3, P300 and ELF1. We identified additional risk loci with low Bayesian false discovery probability (BFDP) scores, indicating they are likely to be true risk associations (BFDP <10%). At chromosome 20q11.22, rs74272064 was associated with HGSOC risk (OR = 1.27, P = 9.0 × 10). Overall EOC risk was associated with rs10260419 at chromosome 7p21.3 (OR = 1.33, P = 1.2 × 10) and rs74917072 at chromosome 2q37.3 (OR = 1.25, P = 4.7 × 10). At 2q37.3, expression quantitative trait locus analysis in 404 HGSOC tissues identified ESPNL as a putative candidate susceptibility gene (P = 1.2 × 10). CONCLUSION:While some risk loci were shared between East Asian and European populations, others were population-specific, indicating that the landscape of EOC risk in Asian women has both shared and unique features compared to women of European ancestry.

关键词： Asian ancestry Enhancer Epithelial ovarian cancer Gene regulation Genome-wide association study eQTL

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Using LICHeE and BAMSE for Reconstructing Cancer Phylogenetic Trees

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Current Protocols in bioinformatics 2018年第1期62卷 e49-e49页

作者： Ricketts, Camir Popic, Victoria Toosi, Hosein Hajirasouliha, Iman Tri-I Computational Biology & Medicine Graduate Program Cornell University New York NY United States Institute for Computational Biomedicine Department of Physiology and Biophysics Weill Cornell Medicine New York NY United States Illumina Inc. Illumina Mission Bay San Francisco CA United States Department of Bioinformatics Institute for Biochemistry and Biophysics University of Tehran Iran Englander Institute for Precision Medicine The Meyer Cancer Center Weill Cornell Medicine New York United States

The reconstruction of cancer phylogeny trees and quantifying the evolution of the disease is a challenging task. LICHeE and BAMSE are two computational tools designed and implemented recently for this purpose. They both utilize estimated variant allele fraction of somatic mutations across multiple samples to infer the most likely cancer phylogenies. This unit provides extensive guidelines for installing and running both LICHeE and BAMSE. © 2018 by John Wiley & Sons, Inc. © 2018 John Wiley & Sons, Inc.

关键词： cancer phylogeny deep sequencing next-generation sequencing somatic variations tumor heterogeneity

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Functional annotation of chemical libraries across diverse biological processes (vol 13, pg 982, 2017)

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NATURE CHEMICAL BIOLOGY 2017年第12期13卷 1286-1286页

作者： Piotrowski, Jeff S. Li, Sheena C. Deshpande, Raamesh Simpkins, Scott W. Nelson, Justin Yashiroda, Yoko Barber, Jacqueline M. Safizadeh, Hamid Wilson, Erin Okada, Hiroki Gebre, Abraham A. Kubo, Karen Torres, Nikko P. LeBlanc, Marissa A. Andrusiak, Kerry Okamoto, Reika Yoshimura, Mami DeRango-Adem, Eva van Leeuwen, Jolanda Shirahige, Katsuhiko Baryshnikova, Anastasia Brown, Grant W. Hirano, Hiroyuki Costanzo, Michael Andrews, Brenda Ohya, Yoshikazu Osada, Hiroyuki Yoshida, Minoru Myers, Chad L. Boone, Charles RIKEN Center for Sustainable Resource Science Wako Saitama Japan Department of Computer Science and Engineering University of Minnesota-Twin Cities Minneapolis Minnesota USA Bioinformatics and Computational Biology Program University of Minnesota-Twin Cities Minneapolis Minnesota USA Department of Electrical and Computer Engineering University of Minnesota-Twin Cities Minneapolis Minnesota USA Department of Integrated Biosciences Graduate School of Frontier Sciences University of Tokyo Kashiwa Chiba Japan Donnelly Centre University of Toronto Toronto Ontario Canada Institute of Molecular and Cellular Biosciences Center for Epigenetic Disease University of Tokyo Bunkyo-ku Tokyo Japan Lewis-Sigler Institute for Integrative Genomics Princeton University Princeton New Jersey USA Department of Biochemistry University of Toronto Toronto Ontario Canada.

Chemical-genetic approaches offer the potential for unbiased functional annotation of chemical libraries. Mutations can alter the response of cells in the presence of a compound, revealing chemical-genetic interactions that can elucidate a compound’s mode of action. We developed a highly parallel, unbiased yeast chemical-genetic screening system involving three key components. First, in a drug-sensitive genetic background, we constructed an optimized diagnostic mutant collection that is predictive for all major yeast biological processes. Second, we implemented a multiplexed (768-plex) barcode-sequencing protocol, enabling the assembly of thousands of chemical-genetic profiles. Finally, based on comparison of the chemical-genetic profiles with a compendium of genome-wide genetic interaction profiles, we predicted compound functionality. Applying this high-throughput approach, we screened seven different compound libraries and annotated their functional diversity. We further validated biological process predictions, prioritized a diverse set of compounds, and identified compounds that appear to have dual modes of action.

关键词： Chemical genetics High-throughput screening Networks and systems biology Target identification

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