文献

J-GLOBAL ID：202102236630034645   整理番号：21A0343029

マルチオミクスデータの変換ネットワークモデリングは,アルツハイマー病に対する詳細な回路,重要な調節因子および潜在的な治療を明らかにする【JST・京大機械翻訳】

Transformative Network Modeling of Multi-omics Data Reveals Detailed Circuits, Key Regulators, and Potential Therapeutics for Alzheimer’s Disease

著者 (114件)： Wang Minghui (Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Wang Minghui (Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Wang Minghui (Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Li Aiqun (Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Li Aiqun (Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Li Aiqun (Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA) ,  Li Aiqun (Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA) ,  Li Aiqun (Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA) ,  Sekiya Michiko (Department of Alzheimer’s Disease Research, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511, Japan) ,  Sekiya Michiko (Department of Experimental Gerontology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, Japan) ,  Beckmann Noam D. (Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Beckmann Noam D. (Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Quan Xiuming (Department of Alzheimer’s Disease Research, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511, Japan) ,  Schrode Nadine (Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Schrode Nadine (Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA) ,  Schrode Nadine (Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA) ,  Schrode Nadine (Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA) ,  Fernando Michael B. (Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Fernando Michael B. (Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA) ,  Fernando Michael B. (Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA) ,  Fernando Michael B. (Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA) ,  Yu Alex (Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Yu Alex (Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA) ,  Yu Alex (Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA) ,  Yu Alex (Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA) ,  Zhu Li (Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA) ,  Zhu Li (Alzheimer’s Disease Research Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA) ,  Zhu Li (Neurology, JJ Peters VA Medical Center, 130 West Kingsbridge Road, Bronx, NY 10468, USA) ,  Cao Jiqing (Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA) ,  Cao Jiqing (Alzheimer’s Disease Research Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA) ,  Cao Jiqing (Neurology, JJ Peters VA Medical Center, 130 West Kingsbridge Road, Bronx, NY 10468, USA) ,  Lyu Liwei (Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Lyu Liwei (Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA) ,  Lyu Liwei (Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA) ,  Lyu Liwei (Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA) ,  Horgusluoglu Emrin (Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Horgusluoglu Emrin (Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Horgusluoglu Emrin (Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Wang Qian (Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Wang Qian (Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Wang Qian (Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Guo Lei (Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Guo Lei (Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Guo Lei (Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Wang Yuan-shuo (Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Wang Yuan-shuo (Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Wang Yuan-shuo (Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Neff Ryan (Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Neff Ryan (Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Neff Ryan (Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Song Won-min (Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Song Won-min (Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Song Won-min (Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Wang Erming (Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Wang Erming (Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Wang Erming (Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Shen Qi (Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Shen Qi (Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Shen Qi (Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Zhou Xianxiao (Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Zhou Xianxiao (Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Zhou Xianxiao (Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Ming Chen (Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Ming Chen (Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Ming Chen (Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Ho Seok-Man (Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Ho Seok-Man (Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA) ,  Ho Seok-Man (Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA) ,  Ho Seok-Man (Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA) ,  Vatansever Sezen (Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Vatansever Sezen (Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Vatansever Sezen (Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Kaniskan H. UEmit (Department of Pharmacological Sciences and Oncological Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA) ,  Kaniskan H. UEmit (Mount Sinai Center for Therapeutics Discovery, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA) ,  Jin Jian (Department of Pharmacological Sciences and Oncological Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA) ,  Jin Jian (Mount Sinai Center for Therapeutics Discovery, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA) ,  Jin Jian (Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA) ,  Zhou Ming-Ming (Department of Pharmacological Sciences and Oncological Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA) ,  Ando Kanae (Department of Biological Sciences, Graduate School of Science, Tokyo Metropolitan University, Tokyo 192-0397, Japan) ,  Ho Lap (Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Ho Lap (Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Ho Lap (Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Slesinger Paul A. (Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA) ,  Slesinger Paul A. (Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA) ,  Yue Zhenyu (Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA) ,  Zhu Jun (Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Zhu Jun (Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Katsel Pavel (Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA) ,  Katsel Pavel (Psychiatry, JJ Peters VA Medical Center, 130 West Kingsbridge Road, Bronx, NY 10468, USA) ,  Gandy Sam (Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA) ,  Gandy Sam (Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA) ,  Gandy Sam (Alzheimer’s Disease Research Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA) ,  Ehrlich Michelle E. (Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA) ,  Ehrlich Michelle E. (Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA) ,  Fossati Valentina (The New York Stem Cell Foundation Research Institute, New York, NY 10019, USA) ,  Noggle Scott (The New York Stem Cell Foundation Research Institute, New York, NY 10019, USA) ,  Cai Dongming (Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA) ,  Cai Dongming (Alzheimer’s Disease Research Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA) ,  Cai Dongming (Neurology, JJ Peters VA Medical Center, 130 West Kingsbridge Road, Bronx, NY 10468, USA) ,  Haroutunian Vahram (Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA) ,  Haroutunian Vahram (Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA) ,  Haroutunian Vahram (Alzheimer’s Disease Research Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA) ,  Haroutunian Vahram (Psychiatry, JJ Peters VA Medical Center, 130 West Kingsbridge Road, Bronx, NY 10468, USA) ,  Iijima Koichi M. (Department of Alzheimer’s Disease Research, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511, Japan) ,  Iijima Koichi M. (Department of Experimental Gerontology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, Japan) ,  Schadt Eric (Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Schadt Eric (Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Brennand Kristen J. (Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Brennand Kristen J. (Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA) ,  Brennand Kristen J. (Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA) ,  Brennand Kristen J. (Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA) ,  Zhang Bin (Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Zhang Bin (Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA) ,  Zhang Bin (Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA)
資料名： Neuron  (Neuron)
巻： 109  号： 2  ページ： 257-272.e14  発行年： 2021年 
JST資料番号： T0649A  ISSN： 0896-6273  資料種別： 逐次刊行物 (A)
記事区分： 原著論文  発行国： オランダ (NLD)  言語： 英語 (EN)

抄録/ポイント： 後期発症Alzheimer病(LOAD)の分子機構と新規治療標的を同定するために,著者らは,異なる認知と神経病理学的表現型を有する364人のドナーにわたる4つの皮質領域のマルチオミクスプロファイリングの統合ネットワーク分析を行った。著者らの分析は,LOADにおいて最も調節不全として,数千の分子的変化を明らかにし,ニューロン遺伝子サブネットワークを明らかにした。ATP6V1Aをトップランクニューロンサブネットワークの重要な調節因子として同定し,疾患関連過程におけるその役割を,ヒト誘導多能性幹細胞由来ニューロンにおけるCRISPRに基づく操作およびショウジョウバエモデルにおけるRNAiに基づくノックダウンにより評価した。ATP6V1A欠損による神経機能障害と神経変性は,再配置化合物NCH-51により改善された。本研究は,LOADにより影響を受ける重要な脳領域における複雑な分子相互作用の詳細なシグナル伝達回路だけでなく,全体的景観も提供し,得られたネットワークモデルはLOADに対する次世代治療薬を開発するための青写真として役立つであろう。Copyright 2021 Elsevier B.V., Amsterdam. All rights reserved. Translated from English into Japanese by JST.【JST・京大機械翻訳】

シソーラス用語： ドナー ,  分子間相互作用 ,  *ネットワーク ,  ニューロン ,  遺伝子 ,  ヒト ,  表現型 ,  皮質 ,  *Alzheimer病 ,  RNA干渉 ,  *調節因子 ,  *オミックス ,  ショウジョウバエ属 ,  シグナル伝達 ,  遺伝 ,  ハエ目 ,  無脊椎動物
準シソーラス用語： ショウジョウバエ ,  細胞情報伝達 ,  神経変性 , 【Automatic Indexing@JST】

著者キーワード (9件)： アルツハイマー病 ,  オミクス ,  ネットワーク生物学 ,  神経調節不全 ,  ATP6V1A ,  ヒト人工多能性幹細胞 ,  NGN2ニューロン ,  ショウジョウバエ ,  NCH-51

分類 (5件)： 分子・遺伝情報処理  (JE15040B) ,  細胞生理一般  (EF02010S) ,  中枢神経系  (EJ12030F) ,  神経の基礎医学  (GN01020W) ,  遺伝子発現  (EC02040Q)

タイトルに関連する用語 (5件)： マルチオミクス ,  ネットワークモデリング ,  アルツハイマー ,  調節因子 ,  治療