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Genome-wide Studies Reveal Genetic Risk Factors for Hepatic Fat Content

Genomics, Proteomics & bioinformatics 2024年第2期22卷 57-68页

作者： Yanni Li Eline H.van den Berg Alexander Kurilshikov Dasha V.Zhernakova Ranko Gacesa Shixian Hu Esteban A.Lopera-Maya Alexandra Zhernakova Lifelines Cohort Study Vincent E.de Meijer Serena Sanna Robin P.F.Dullaart Hans Blokzijl Eleonora A.M.Festen Jingyuan Fu Rinse K.Weersma Department of Gastroenterology and Hepatology University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands Department of Genetics University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands Department of Gastroenterology and Hepatology Tianjin Medical University General HospitalTianjin Medical UniversityTianjin 300052China Laboratory of Genomic Diversity Center for Computer TechnologiesITMO UniversitySaint Petersburg 199034Russia Institute of Precision Medicine the First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China Department of Surgery Section of Hepatobiliary Surgery and Liver TransplantationUniversity of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands Department of Endocrinology University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands Department of Pediatrics University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands 不详

Genetic susceptibility to metabolic associated fatty liver disease(MAFLD)is complex and poorly *** characterization of the genetic background of hepatic fat content would provide insights into disease etiology and causality of risk *** performed genome-wide association study(GWAS)on two noninvasive definitions of hepatic fat content:magnetic resonance imaging proton density fat fraction(MRI-PDFF)in 16,050 participants and fatty liver index(FLI)in 388,701 participants from the United Kingdom(UK)Biobank(UKBB).Heritability,genetic overlap,and similarity between hepatic fat content phenotypes were analyzed,and replicated in 10,398 participants from the University Medical Center groningen(UMCG)Genetics Lifelines Initiative(UGLI).Meta-analysis of GWASs of MRI-PDFF in UKBB revealed five statistically significant loci,including two novel genomic loci harboring CREB3L1(rs72910057-T,P=5.40E−09)and GCM1(rs1491489378-T,P=3.16E−09),respectively,as well as three previously reported loci:PNPLA3,TM6SF2,and *** of FLI in UKBB identified 196 genome-wide significant loci,of which 49 were replicated in UGLI,with top signals in ZPR1(P=3.35E−13)and FTO(P=2.11E−09).Statistically significant genetic correlation(rg)between MRI-PDFF(UKBB)and FLI(UGLI)GWAS results was found(rg=0.5276,P=1.45E−03).Novel MRI-PDFF genetic signals(CREB3L1 and GCM1)were replicated in the FLI *** identified two novel genes for MRI-PDFF and 49 replicable loci for *** a difference in hepatic fat content assessment between MRI-PDFF and FLI,a substantial similar genetic architecture was *** is identified as an easy and reliable approach to study hepatic fat content at the population level.

关键词： Hepatic fat content MAFLD Genome-wide association study Fatty liver index Magnetic resonance imaging proton density fat fraction

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Age structure in neutral theory resolves inconsistencies related to reproductive-size threshold

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Journal of Plant Ecology 2012年第1期5卷 64-71页

作者： James Rosindell Patrick A.Jansen Rampal S.Etienne Institute of Integrative and Comparative Biology Faculty of Biological SciencesUniversity of LeedsLeeds LS29JTWest YorkshireUK Institute of bioinformatics and Evolutionary Studies University of IdahoMoscowID 83844USA Center for Tropical Forest Science Smithsonian Tropical Research InstitutePO Box 0843-03092BalboaAnconRepublic of Panama centre of Ecosystem Studies Wageningen UniversityPO Box 476700 AA Wageningenthe Netherlands Community and Conservation Ecology Centre for Ecological and Evolutionary StudiesUniversity of GroningenPO Box 111039700 CC Groningenthe Netherlands

Aims Neutral theory consists of a suite of models that assume ecological equivalence among individual *** have been most commonly applied to tropical forest tree communities either as null models or as *** models typically only include reproductive adults;therefore,fitting to empirical tree community data requires defining a reproductive-size threshold,which for trees is usually set arbitrarily to a diameter at breast height(DBH)of 100 *** inevitable exclusion of some reproductive adults and inclusion of some saplings cause a non-random sampling bias in neutral model ***,we investigate this problem and resolve it by introducing simple age structure into a neutral *** We compared the performance and sensitivity of DBH threshold of three variants of a spatially explicit neutral model:the traditional model,a model incorporating random sampling and a model with two distinct age classes—reproductive adults and *** the age-structured model,saplings are offspring from adults that disperse according to a Gaussian dispersal kernel around the *** only extra parameter is the ratio of adults to saplings,which is not a free parameter but directly *** used species–area relationships(SARs)to explore the predicted effect of saplings on the species richness at different scales in our *** then evaluated the three model variations to find the parameters required to maintain the observed level of species richness in the 50-ha plot on Barro Colorado Island(BCI).We repeated our analysis filtering the data at different minimum tree-size thresholds in order to find the effect this threshold has on our ***,we used empirical species–individual relationships(SIRs)to test the pre-existing hypothesis that environmental filtering is the primary cause of differences between the assemblage of saplings and that of adults on *** Findings Our age-structured neutral model was characterized by SARs that

关键词： neutral theory age structure sampling DBH

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Coronatine-lnsensitive 1 （COI1） Mediates Transcriptional Responses of Arabidopsis thaliana to External Potassium Supply

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Molecular Plant 2010年第2期3卷 390-405页

作者： Patrick Armengaud Rainer Breitling Anna Amtmann Faculty of Biomedical and Life Sciences University of Glasgow Glasgow G12 8QQ UK Present address: Institut National de la Recherche Agronomique Unite de nutrition azotee des plantes RD10 78026 Versailles Cedex France groningen bioinformatics centre University of Groningen Kerklaan 30 9751 NN Haren The Netherlands

The ability to adjust growth and development to the availability of mineral nutrients in the soil is an essential life skill of plants but the underlying signaling pathways are poorly understood. In Arab/dops/s thal/ana, shortage of po- tassium （K） induces a number of genes related to the phytohormone jasmonic acid （JA）. Using comparative microarray analysis of wild-type and coi1-16 mutant plants, we classified transcriptional responses to K with respect to their depen- dence on COI1, a central component of oxylipin signaling. Expression profiles obtained in a short-term experiment clearly distinguished between COil-dependent and COil-independent K-responsive genes, and identified both known and novel targets of JA-COIl-signaling. During long-term K-deficiency, coi-16 mutants displayed de novo responses covering similar functions as COil-targets except for defense. A putative role of JA for enhancing the defense potential of K-deficient plants was further supported by the observation that plants grown on low K were less damaged by thrips than plants grown with sufficient K.

关键词： Hormonal regulation nutrition secondary metabolism/natural products transcriptome analysis plantinsect interactions Arabidopsis.

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Systematics of the avian family Alaudidae using multilocus and genomic data

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Avian Research 2023年第2期14卷 137-152页

作者： Per Alstrom Zeinolabedin Mohammadi Erik D.Enbody Martin Irestedt Derek Engelbrecht Pierre-Andre Crochet Alban Guillaumet Loïs Rancilhac B.Irene Tieleman Urban Olsson Paul F.Donald Martin Stervander Animal Ecology Department of Ecology and GeneticsEvolutionary Biology CentreUppsala UniversityNorbyvagen 18DSE-75236UppsalaSweden Key Laboratory of Zoological Systematics and Evolution Institute of ZoologyChinese Academy of SciencesBeijing100101China Department of Biology Faculty of SciencesGolestan UniversityGorganGolestanIran Department of Medical Biochemistry and Microbiology Uppsala University75123UppsalaSweden Department of Biomolecular Engineering University of CaliforniaSanta Cruz95060Santa CruzCAUSA Department of bioinformatics and Genetics Swedish Museum of Natural HistoryP.O.Box 50007SE-10405StockholmSweden Department of Biodiversity University of LimpopoPrivate Bag X1106Sovenga0727South Africa CEFE CNRSUniv MontpellierEPHEIRDMontpellierFrance Department of Biological&Environmental Sciences Troy UniversityTroyAL36082USA groningen Institute for Evolutionary Life Sciences University of GroningenNijenborgh 79747 AGGroningenthe Netherlands Department of Biological and Environmental Sciences University of GothenburgP.O.Box 463SE-40530GothenburgSweden Gothenburg Global Biodiversity centre P.O.Box 461SE-40530GothenburgSweden BirdLife International The David Attenborough BuildingPembroke StCambridgeCB23QZUK Department of Zoology University of CambridgeDowning StreetCambridgeCB23EJUK Bird Group Natural History MuseumAkeman StreetTringHertfordshireHP236APUnited Kingdom

The family Alaudidae,larks,comprises 93-100 species(depending on taxonomy)that are widely distributed across Africa and Eurasia,with single species extending their ranges to North and northernmost South America and Australia.A decade-old molecular phylogeny,comprising~80%of the species,revealed multiple cases of parallel evolution and large variation in rates of morphological evolution,which had misled taxonomists into creating many non-monophyletic ***,we reconstruct the phylogeny of the larks,using a dataset covering one mitochondrial and 16 nuclear loci and comprising all except one of the currently recognised species as well as several recently proposed new species(in total 133 taxa;not all loci available for all species).We provide additional support using genome-wide markers to infer a genus-level phylogeny based on near-complete generic sampling(in total 51 samples of 44 taxa across 40 species).Our results confirm the previous findings of rampant morphological convergence and divergence,and reveal new cases of paraphyletic *** propose a new subfamily classification,and also that the genus Mirafra is divided into four genera to produce a more balanced generic classification of the *** study supports recently proposed species splits as well as some recent lumps,while also questioning some of the *** comprehensive phylogeny will form an important basis for future studies,such as comparative studies of lark natural history,ecology,evolution and conservation.

关键词： Phylogeny Phylogenomics Multispecies coalescent Lark Paraphyly Taxonomy Subfamily description

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Building Expertise on FAIR Through Evolving Bring Your Own Data(BYOD) Workshops: Describing the Data, Software, and Management-focused Approaches and Their Evolution

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Data Intelligence 2024年第2期6卷 429-456页

作者： César H.Bernabé Lieze Thielemans Rajaram Kaliyaperumal Claudio Carta Shuxin Zhang Celia W.G.van Gelder Nirupama Benis Luiz Olavo Bonino da Silva Santos Ronald Cornet Bruna dos Santos Vieira Nawel Lalout Ines Henriques Alberto Camara Ballesteros Kees Burger Martijn G.Kersloot Friederike Ehrhart Esther van Enckevort Chris T.Evelo Alasdair J.G.Gray Marc Hanauer Kristina Hettne Joep de Ligt Arnaldo Pereira Nuria Queralt-Rosinach Erik Schultes Domenica Taruscio Andra Waagmeester Mark D.Wilkinson Egon L.Willighagen Mascha Jansen Barend Mons Marco Roos Annika Jacobsen Biosemantics Group Department of Human GeneticsLeiden University Medical CentreLeidenThe Netherlands NIHR Academic Fellow in General Practice University College London and The Royal Free NHS Foundation Trust National centre for Rare Diseases Istituto Superiore di SanitaRomeItaly Department of Medical Informatics Amsterdam UMC location University of AmsterdamMeibergdreef 9AmsterdamThe Netherlands Amsterdam Public Health Methodology&Digital HealthAmsterdamThe Netherlands Health-Rl UtrechtThe Netherlands Semantics Services and Cybersecurity groupUniversity of TwenteEnschedeThe Netherlands Department of Medical Imaging Radboud Institute for Health SciencesRadboud University Medical CenterNijmegenThe Netherlands Department of Medical BioSciences Radboud University Medical CenterNijmegenThe Netherlands The Duchenne Parent Project VeneendaalThe Netherlands Departamento de Biotecnologia-Biologia Vegetal Escuela Tecnica Superior de Ingenieria AgronomicaAlimentaria y de BiosistemasCentro de Biotecnologia y Genomica de PlantasUniversidad Politecnica de Madrid(UPM)-Instituto Nacional de Investigacion y Tecnologia Agraria y Alimentaria-CSIC(INIA-CSIC).Campus MontegancedoPozuelo de Alarcon(Madrid)Spain Castor AmsterdamThe Netherlands Department of bioinformatics-BiGCaT Maastricht UniversityMaastrichtThe Netherlands University Medical Center groningen University of GroningenGroningenThe Netherlands Maastricht centre for Systems Biology(MaCSBio) Maastricht UniversityMaastrichtThe Netherlands Department of Computer Science Heriot-Watt UniversityEdinburghUK INSERM US14-OrphanetPlateforme Maladies RaresParisFrance centre for Digital Scholarship Leiden University LibrariesThe Netherlands Center for Molecular Medicine Cancer Genomics NetherlandsDepartment of GeneticsUniversity Medical Center UtrechtUniversity UtrechtThe Netherlands University of Aveiro DETI/IEETAAveiroPortugal GO FAIR Foundation LeidenThe Netherlands The Leiden Academic Center for Drug Research LeidenThe Netherlands Micel

Since 2014,"Bring Your Own Data"workshops(BYODs)have been organised to inform people about the process and benefits of making resources Findable,Accessible,Interoperable,and Reusable(FAIR,and the FAIRification process).The BYOD workshops'content and format differ depending on their goal,context,and the background and needs of ***-focused BYODs educate domain experts on how to make their data FAIR to find new answers to research ***-focused BYODs promote the benefits of making data FAIR and instruct project managers and policy-makers on the characteristics of FAIRification ***-focused BYODs gather software developers and experts on FAIR to implement or improve software resources that are used to support ***,these BYODs intend to foster collaboration between different types of stakeholders involved in data management,curation,and reuse(*** experts,trainers,developers,data owners,data analysts,FAIR experts).The BYODs also serve as an opportunity to learn what kind of support for FAIRification is needed from different communities and to develop teaching materials based on practical examples and *** this paper,we detail the three different structures of the BYODs and describe examples of early BYODs related to plant breeding data,and rare disease registries and biobanks,which have shaped the structure of the *** discuss the latest insights into making BYODs more productive by leveraging our almost ten years of training experience in these workshops,including successes and encountered ***,we examine how the participants'feedback has motivated the research on FAIR,including the development of workflows and software.

关键词： FAIR FAIRification FAIR expertise Bring Your Own Data Workshop BYOD

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Impact of apolipoprotein A1 on tumor immune microenvironment, clinical prognosis and genomic landscape in hepatocellular carcinoma

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Precision Clinical Medicine 2023年第3期6卷 158-171页

作者： Ying Wang Shipeng Chen Xiao Xiao Fan Yang Jinhan Wange Hui Zong Yuzhen Gao Chenjun Huang Xuewen Xu Meng Fang Xiaoyan Zhang Chunfang Gao Clinical Laboratory Medicine Center Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghai200437China Department of Laboratory Medicine Shanghai Eastern Hepatobiliary Surgery HospitalShanghai 200438China Research Center for Translational Medicine Shanghai East HospitalSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Department of Medical Microbiology and Infection Prevention Tumor Virology and Cancer ImmunotherapyUniversity Medical Center GroningenUniversity of GroningenGroningen 9712 CPThe Netherlands State Key Laboratory for Diagnosis and Treatment of Infectious Diseases The First Affliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310058China Department of Hepatobiliary and Pancreatic Surgery Shanghai East HospitalTongji University School of MedicineShanghai 200120China Institutes for Systems Genetics Frontiers Science Center for Disease-Related Molecular NetworkWest China HospitalSichuan UniversityChengdu 610041China Department of Clinical Laboratory Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou 310058China

Background:Current knowledge on apolipoprotein A1(APOA1)in hepatocellular carcinoma(HCC)is fragmented and even ***-dimensional analyses are required to comprehensively elucidate its value and underlying ***:We collected 49 RNA-seq datasets,40 cell line types data and 70 scRNA pan-cancer datasets public available,including 17 HCC datasets(1754 tumor samples),and enrolled 73 pairs of HCC tissue and 516 blood samples independently from our ***1 impacting on the HCC tumor microenvironment(TME)was analyzed using intensive data *** sequencing,flow cy-tometry,quantitative PCR,western blot,immunohistochemistry and clinical chemistry assays were conducted for wet experimental ***:The APOA1 ontology fingerprint indicated that it played various crucial biological roles in HCC,primarily involved in choles-terol *** findings at histology,serology,and clinical follow-up revealed that high APOA1 was a good prognosis indicator of *** in the APOA1 promoter region was found in clinical samples which is in accordance with the reduction of APOA1 in *** cell cycle,DNA replication,mismatch repair pathways,and tumor cell proliferation were less observed in the HCC APOAihigh *** favorable immunoregulatory abilities of APOA1 showed interesting findings:a positive correlation between APOA1 and anti-tumor immune cells(NK,CD8+T cells)and a negative association with immune cells exerting immunosuppressive effects,including M2 ***:This is an integrative multidimensional exploration of APOA1 using bioinformatics and *** the prognostic value and anti-tumor effects based on APOA1 panoramic exploration in the HCC TME demonstrate a new potential clinicai target for HCC assessment and intervention in the future.

关键词： APOA1 HCC prognosis tumor microenvironment immune cells NK cell

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New Algorithm for MALDI-TOF MS Fingerprinting Based Bacterial Identification

New Algorithm for MALDI-TOF MS Fingerprinting Based Bacteria...

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2018年中国质谱学术大会（CMSC2018）

作者： Liang Qiao Yi Yang Ding Cheng Yu Lin Peter Horvatovich Department of Chemistry Fudan University Research School of Computer Science College of Engineering and Computer ScienceThe Australian National University Department of Pharmacy University of Groningen

Bacterial typing is of great importance in clinical diagnosis, environmental monitoring, food safety analysis, and biological research. Matrix-assisted laser desorption/ionization mass spectrometry(MALDI-MS) is now widely used to analyze bacterial samples. Identification of bacteria at the species level can be realized by matching the mass spectra of samples against a library of mass spectra of known bacteria. Nevertheless, in order to reasonably type bacteria, identification accuracy should be further improved. We have developed a set of bioinformatics tools for bacterial identification using MALDI-TOF mass spectra. For isolated pure cultures, our approach combines new measures for spectra similarity and a novel bootstrapping assessment. [1] We tested our approach on a general data set containing the mass spectra of 1741 strains of bacteria and another challenging data set containing 250 strains, including 40 strains in the Bacillus cereus group that were previously claimed to be impossible to resolve by MALDI-MS. With the bootstrapping assessment, we achieved much more reliable predictions at both the genus and species level, and enabled to resolve the Bacillus cereus group. For bacterial mixtures, the framework is a combination of a synthetic mixture model based on a non-negative linear combination of candidate reference spectra and a statistical assessment by in silico generated spectra via a jackknife resampling. [2] Ninety-seven model bacterial mixture samples and 8 co-cultured blind-coded bacterial mixture samples, containing up to 6 strains in varied ratios in each sample, together with a reference database containing the mass spectra of 1081 strains, were used to validate the framework. High sensitivity(>80%, with error rate <5%) was achieved for balanced binary and ternary mixtures. Spectral library generation requires acquisition of MALDI-TOF spectra from monoculture bacterial colonies, which is time-consuming and not possible for many species and strains

关键词： MALDI-TOF MS bacterial identification bioinformatics statistical assessment

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