Advancing drug repositioning and development for Alzheimer's Disease using functional genomics and computational phenomics
利用功能基因组学和计算表型组学推进阿尔茨海默病的药物重新定位和开发
基本信息
- 批准号:10459749
- 负责人:
- 金额:$ 75.6万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-05 至 2023-08-31
- 项目状态:已结题
- 来源:
- 关键词:AffectAlzheimer&aposs DiseaseAlzheimer&aposs Disease PathwayAlzheimer&aposs disease diagnosisAlzheimer&aposs disease modelAlzheimer&aposs disease therapeuticAnimal ModelAtlasesBiologicalCatalogsClinical DataCollaborationsCommunitiesComplexComputer softwareComputing MethodologiesData SetDevelopmentDiseaseDrug TargetingEnsureFoundationsFutureGene ExpressionGenesGeneticGenetic TranscriptionGenomicsHeritabilityHumanImmuneIndividualInfrastructureLiverLongevityMachine LearningMapsMeta-AnalysisMethodologyMicrogliaModelingMolecularNeurodegenerative DisordersPatientsPeripheralPharmaceutical PreparationsPhasePhenotypePhysiologyPopulationPrevalenceProxyRecording of previous eventsResearchResourcesRoleSingle Nucleotide PolymorphismSpleenSymptomsTissuesUntranslated RNAValidationVariantWhole BloodZebrafishabeta depositionadvanced analyticsbiobankbrain cellcausal variantclinical Diagnosiscomorbiditydifferential expressiondrug developmentdrug repurposingextracellularfunctional genomicsgenetic risk factorgenome wide association studygenomic datagenomic locushuman diseasehyperphosphorylated tauimprovedinnovationinsightnetwork modelsnew therapeutic targetnovel therapeuticsopen sourcephenomephenomicsprogramspublic health relevanceside effectsuccesstherapeutic developmenttraittranscriptome
项目摘要
PROJECT SUMMARY
Alzheimer’s disease (AD) is a heterogeneous neurodegenerative disorder which is highly
prevalent in the global population, affecting around 46 million individuals. Due to increased
longevity, the prevalence is rising. AD is characterized pathophysiologically by extracellular β-
amyloid deposition and intracellular hyperphosphorylated tau. Current medications for AD
provide some relief from disease symptoms but are not effective in all patients while severe side
effects are observed. The disease is highly heritable and has a complex molecular basis, with a
substantial polygenic component.
There is an urgent need for developing approaches to target discovery and drug repurposing.
The combination of methodological analytic advances, functional genomics data, and
phenotype-rich datasets can be the foundation for identifying new therapies. Our central
hypothesis is that an integrative approach spanning human phenomics and genomics will offer
new AD therapeutic possibilities, including drug repositioning, and provide a powerful approach
to drug target discovery. We will develop cutting-edge genetics-anchored computational
methodologies for AD drug repurposing, generate a community resource to advance research in
AD therapeutics development, leverage a collaboration (infrastructure and machine learning)
with Google, and conduct target validation in a zebrafish model of AD.
We have engaged an interdisciplinary team to ensure the success and broad impact of our
proposal and lay the groundwork for future innovative research.
项目摘要
阿尔茨海默病(Alzheimer's disease,AD)是一种异质性神经退行性疾病,
在全球人群中流行,影响约4600万人。由于增加
长寿,患病率正在上升。AD的病理生理特征是细胞外β-
淀粉样蛋白沉积和细胞内过度磷酸化tau。目前的AD药物
对疾病症状有一定的缓解作用,但并非对所有患者都有效,
观察效果。该疾病具有高度遗传性,具有复杂的分子基础,
大量的多基因成分。
迫切需要开发靶点发现和药物再利用的方法。
结合方法分析的进展,功能基因组学数据,
表型丰富的数据集可以成为识别新疗法的基础。我们的中央
假设是,跨越人类表型组学和基因组学的综合方法将提供
新的AD治疗可能性,包括药物重新定位,并提供了一种强有力的方法
to drug药物target目标discovery发现.我们将开发尖端的基因锚定计算
AD药物再利用的方法,产生一个社区资源,以推进研究,
AD疗法开发,利用协作(基础设施和机器学习)
与谷歌合作,并在AD的斑马鱼模型中进行目标验证。
我们聘请了一个跨学科的团队,以确保我们的成功和广泛的影响,
并为未来的创新研究奠定基础。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Eric R Gamazon其他文献
ラウンドテーブル アナボリック・アンドロジェニック・ステロイド(パート2)
圆桌会议合成代谢和雄激素类固醇(第 2 部分)
- DOI:
- 发表时间:
2008 - 期刊:
- 影响因子:0
- 作者:
Alisa Manning;Heather M Highland;J. Gasser;Xueling Sim;Taru Tukiainen;Pierre Fontanillas;Niels Grarup;Manuel A Rivas;Anubha Mahajan;Adam E Locke;Pablo Cingolani;Tune H Pers;Ana Viñuela;Andrew Brown;Ying Wu;Jason Flannick;Christian Fuchsberger;Eric R Gamazon;Kyle J Gaulton;Hae Kyung Im;Tanya M Teslovich;Thomas W Blackwell;Jette Bork;Noël P Burtt;Yuhui Chen;T. Green;Christopher Hartl;Hyun Min Kang;Ashish Kumar;Claes Ladenvall;Clement Ma;Loukas Moutsianas;Richard D Pearson;John R B Perry;N. Rayner;Neil R Robertson;Laura J Scott;Martijn van de Bunt;Johan G Eriksson;Antti Jula;Seppo Koskinen;Terho Lehtimäki;Aarno Palotie;Olli T Raitakari;Suzanne BR Jacobs;J. Wessel;Audrey Y Chu;Robert A. Scott;Mark O Goodarzi;Christine Blancher;Gemma Buck;David Buck;Peter S Chines;Stacey Gabriel;Anette P Gjesing;Christopher J Groves;Mette Hollensted;Jeroen R Huyghe;Anne U Jackson;Goo Jun;Johanne Marie Justesen;Massimo Mangino;J. Murphy;Matt Neville;Robert Onofrio;Kerrin S Small;Heather M Stringham;Joseph Trakalo;Eric Banks;Jason Carey;Mauricio O Carneiro;Mark DePristo;Yossi Farjoun;Timothy J. Fennell;Jacqueline I Goldstein;George Grant;Martin Hrabé de Angelis;J. Maguire;Benjamin M Neale;Ryan Poplin;Shaun M Purcell;Thomas Schwarzmayr;Khalid Shakir;Joshua D Smith;Tim M. Strom;Thomas Wieland;Jaana Lindstrom;Ivan Brandslund;Cramer Christensen;Gabriela L Surdulescu;Timo A Lakka;Alex S F Doney;Peter Nilsson;Nicholas J Wareham;C. Langenberg;Tibor V Varga;Paul W Franks;Olov Rolandsson;Anders H Rosengren;Vidya S Farook;Farook Thameem;Sobha Puppala;Satish Kumar;Donna M Lehman;Christopher P Jenkinson;Joanne E Curran;Daniel Esten Hale;Sharon P Fowler;Rector Arya;Ralph A. DeFronzo;Hanna E Abboud;Ann;Pamela J Hicks;Nicholette D Palmer;Maggie C Y Ng;Donald W Bowden;Barry I Freedman;Tõnu Esko;Reedik Mägi;Lili Milani;Evelin Mihailov;Andres Metspalu;Narisu Narisu;Leena Kinnunen;Lori L Bonnycastle;Amy Swift;Dorota Pasko;Andrew R Wood;João Fadista;Toni I Pollin;Nir Barzilai;Gil Atzmon;Benjamin Glaser;Barbara Thorand;Konstantin Strauch;Annette Peters;Michael Roden;Martina Müller;L. Liang;Jennifer Kriebel;Thomas Illig;Harald Grallert;Christian Gieger;Christa Meisinger;Lars Lannfelt;Solomon K Musani;Michael D. Griswold;Herman A Taylor;G. Wilson;Adolfo Correa;Heikki Oksa;W. R. Scott;Uzma Afzal;Sian;Marie Loh;John C Chambers;Jobanpreet Sehmi;Jaspal Singh Kooner;Benjamin;Lehne;Yoon;Shin;Cho;Jong;Lee;Bok;Han;Annemari Käräjämäki;Qi Qi;Lu Qi;Jinyan Huang;Frank B. Hu;O. Melander;Marju Orho;David Aguilar;Tien Yin Wong;Jianjun Liu;Chiea;Kee Seng Chia;W. Y. Lim;Chingwen Cheng;E. Chan;E. S. Tai;Tin Aung;Allan Linneberg;Bo Isomaa;T. Meitinger;T. Tuomi;Liisa Hakaste;Jasmina Kravic;Marit E Jørgensen;T. Lauritzen;Panos Deloukas;Kathleen E Stirrups;Katharine R Owen;Andrew J Farmer;Timothy M Frayling;Stephen P O'Rahilly;M. Walker;Jonathan C Levy;Dylan Hodgkiss;Andrew T. Hattersley;Teemu Kuulasmaa;Inês Barroso;Dwaipayan Bharadwaj;Juliana Chan;G. R. Chandak;Mark J Daly;Peter J Donnelly;Shah B Ebrahim;Paul Elliott;Tasha Fingerlin;Philippe Froguel;Cheng Hu;Weiping Jia;R. C. Ma;Gilean McVean;Taesung Park;D. Prabhakaran;Manjinder Sandhu;J. Scott;Rob Sladek;Nikhil Tandon;Yik Ying Teo;Eleftheria Zeggini;Richard M Watanabe;Heikki A Koistinen;Y. A. Kesaniemi;Matti Uusitupa;Tim Spector;Veikko Salomaa;Rainer Rauramaa;Colin N A Palmer;Inga Prokopenko;Andrew D Morris;Richard N Bergman;Francis S. Collins;Lars Lind;Erik;Ingelsson;Jaakko;Tuomilehto;Fredrik;Karpe;Leif;Groop;Torben Jørgensen;Torben Hansen;Oluf Pedersen;Johanna Kuusisto;Gonçalo Abecasis - 通讯作者:
Gonçalo Abecasis
Eric R Gamazon的其他文献
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{{ truncateString('Eric R Gamazon', 18)}}的其他基金
Haplotype-aware models of gene and isoform expression with application to genetic studies of disease in diverse populations
基因和亚型表达的单倍型感知模型及其应用于不同人群疾病遗传学研究
- 批准号:
10540421 - 财政年份:2021
- 资助金额:
$ 75.6万 - 项目类别:
Advancing drug repositioning and development for Alzheimer's Disease using functional genomics and computational phenomics
利用功能基因组学和计算表型组学推进阿尔茨海默病的药物重新定位和开发
- 批准号:
10480887 - 财政年份:2021
- 资助金额:
$ 75.6万 - 项目类别:
Haplotype-aware models of gene and isoform expression with application to genetic studies of disease in diverse populations
基因和亚型表达的单倍型感知模型及其应用于不同人群疾病遗传学研究
- 批准号:
10390207 - 财政年份:2021
- 资助金额:
$ 75.6万 - 项目类别:
Haplotype-aware models of gene and isoform expression with application to genetic studies of disease in diverse populations
基因和亚型表达的单倍型感知模型及其应用于不同人群疾病遗传学研究
- 批准号:
10360462 - 财政年份:2021
- 资助金额:
$ 75.6万 - 项目类别:
Advancing Multi-Omics and Electronic Health Records Computational Methodologies
推进多组学和电子健康记录计算方法
- 批准号:
10408099 - 财政年份:2020
- 资助金额:
$ 75.6万 - 项目类别:
Advancing Multi-Omics and Electronic Health Records Computational Methodologies
推进多组学和电子健康记录计算方法
- 批准号:
9979509 - 财政年份:2020
- 资助金额:
$ 75.6万 - 项目类别:
Advancing Multi-Omics and Electronic Health Records Computational Methodologies
推进多组学和电子健康记录计算方法
- 批准号:
10653197 - 财政年份:2020
- 资助金额:
$ 75.6万 - 项目类别: