Single-cell genomics and regulatory networks for 388 human brains.
| العنوان: | Single-cell genomics and regulatory networks for 388 human brains. |
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| المؤلفون: | Emani PS; Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, 06520, USA.; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, 06520, USA., Liu JJ; Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, 06520, USA.; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, 06520, USA., Clarke D; Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, 06520, USA.; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, 06520, USA., Jensen M; Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, 06520, USA.; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, 06520, USA., Warrell J; Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, 06520, USA.; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, 06520, USA., Gupta C; Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI, 53706, USA.; Waisman Center, University of Wisconsin-Madison, Madison, WI, 53705, USA., Meng R; Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, 06520, USA.; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, 06520, USA., Lee CY; Department of Computer Science, University of California, Irvine, CA, 92697, USA., Xu S; Department of Computer Science, University of California, Irvine, CA, 92697, USA., Dursun C; Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, 06520, USA.; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, 06520, USA., Lou S; Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, 06520, USA.; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, 06520, USA., Chen Y; Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, 06520, USA.; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, 06520, USA., Chu Z; Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, 06520, USA., Galeev T; Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, 06520, USA.; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, 06520, USA., Hwang A; Department of Computer Science, University of California, Irvine, CA, 92697, USA.; Mathematical, Computational and Systems Biology, University of California, Irvine, CA, 92697, USA., Li Y; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, 06520, USA.; Department of Computer Science, Yale University, New Haven, CT, 06520, USA., Ni P; Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, 06520, USA.; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, 06520, USA., Zhou X; Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, 06520, USA.; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, 06520, USA., Bakken TE; Allen Institute for Brain Science, Seattle, WA, 98109, USA., Bendl J; Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Bicks L; Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA., Chatterjee T; Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, 06520, USA.; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, 06520, USA., Cheng L; Tempus Labs, Inc., Chicago, IL, 60654, USA., Cheng Y; Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.; Department of Opthalmology, Perlman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA., Dai Y; Department of Computer Science, University of California, Irvine, CA, 92697, USA., Duan Z; Department of Computer Science, University of California, Irvine, CA, 92697, USA., Flaherty M; Tempus Labs, Inc., Chicago, IL, 60654, USA., Fullard JF; Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Gancz M; Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, 06520, USA.; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, 06520, USA., Garrido-Martín D; Department of Genetics, Microbiology and Statistics, Universitat de Barcelona, Barcelona, 08028, Spain., Gaynor-Gillett S; Tempus Labs, Inc., Chicago, IL, 60654, USA.; Department of Biology, Cornell College, Mount Vernon, IA, 52314, USA., Grundman J; Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA., Hawken N; Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA., Henry E; Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, 06520, USA.; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, 06520, USA., Hoffman GE; Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Mental Illness Research Education and Clinical Center, James J. Peters VA Medical Center, Bronx, NY, 10468, USA.; Center for Precision Medicine and Translational Therapeutics, James J. Peters VA Medical Center, Bronx, NY, 10468, USA., Huang A; Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, 06520, USA., Jiang Y; Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, 06520, USA.; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, 06520, USA., Jin T; Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI, 53706, USA.; Waisman Center, University of Wisconsin-Madison, Madison, WI, 53705, USA., Jorstad NL; Allen Institute for Brain Science, Seattle, WA, 98109, USA., Kawaguchi R; Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.; Center for Autism Research and Treatment, Semel Institute, University of California, Los Angeles, CA, 90095, USA., Khullar S; Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI, 53706, USA.; Waisman Center, University of Wisconsin-Madison, Madison, WI, 53705, USA., Liu J; Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA., Liu J; Department of Computer Science, University of California, Irvine, CA, 92697, USA., Liu S; Waisman Center, University of Wisconsin-Madison, Madison, WI, 53705, USA., Ma S; Department of Neuroscience, Yale University, New Haven, CT, 06510, USA.; Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China., Margolis M; Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA., Mazariegos S; Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA., Moore J; Department of Genomics and Computational Biology, UMass Chan Medical School, Worcester, MA, 01605, USA., Moran JR; Tempus Labs, Inc., Chicago, IL, 60654, USA., Nguyen E; Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, 06520, USA.; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, 06520, USA., Phalke N; Department of Genomics and Computational Biology, UMass Chan Medical School, Worcester, MA, 01605, USA., Pjanic M; Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Pratt H; Department of Genomics and Computational Biology, UMass Chan Medical School, Worcester, MA, 01605, USA., Quintero D; Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA., Rajagopalan AS; Department of Computer Science, Yale University, New Haven, CT, 06520, USA., Riesenmy TR; Department of Statistics & Data Science, Yale University, New Haven, CT, 06520, USA., Shedd N; Department of Genomics and Computational Biology, UMass Chan Medical School, Worcester, MA, 01605, USA., Shi M; Tempus Labs, Inc., Chicago, IL, 60654, USA., Spector M; Tempus Labs, Inc., Chicago, IL, 60654, USA., Terwilliger R; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, 06520, USA., Travaglini KJ; Allen Institute for Brain Science, Seattle, WA, 98109, USA., Wamsley B; Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA., Wang G; Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, 06520, USA.; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, 06520, USA., Xia Y; Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, 06520, USA.; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, 06520, USA., Xiao S; Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA., Yang AC; Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, 06520, USA.; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, 06520, USA., Zheng S; Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, 06520, USA.; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, 06520, USA., Gandal MJ; Interdepartmental Program in Bioinformatics, University of California, Los Angeles, Los Angeles, CA, 90095, USA.; Department of Psychiatry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA.; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA.; Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Lifespan Brain Institute, The Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA., Lee D; Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Lein ES; Allen Institute for Brain Science, Seattle, WA, 98109, USA.; Department of Neurological Surgery, University of Washington, Seattle, WA, 98195, USA.; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, 98195, USA., Roussos P; Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Mental Illness Research Education and Clinical Center, James J. Peters VA Medical Center, Bronx, NY, 10468, USA.; Center for Precision Medicine and Translational Therapeutics, James J. Peters VA Medical Center, Bronx, NY, 10468, USA., Sestan N; Department of Neuroscience, Yale University, New Haven, CT, 06510, USA., Weng Z; Department of Genomics and Computational Biology, UMass Chan Medical School, Worcester, MA, 01605, USA., White KP; Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore., Won H; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA., Girgenti MJ; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, 06520, USA.; Wu Tsai Institute, Yale University, New Haven, CT, 06520, USA.; Clinical Neuroscience Division, National Center for Posttraumatic Stress Disorder, Veterans Affairs Connecticut Healthcare System, West Haven, CT, 06516, USA., Zhang J; Department of Computer Science, University of California, Irvine, CA, 92697, USA., Wang D; Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI, 53706, USA.; Waisman Center, University of Wisconsin-Madison, Madison, WI, 53705, USA.; Department of Computer Sciences, University of Wisconsin-Madison, Madison, WI, 53706, USA., Geschwind D; Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.; Center for Autism Research and Treatment, Semel Institute, University of California, Los Angeles, CA, 90095, USA.; Department of Psychiatry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA.; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA.; Institute for Precision Health, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA., Gerstein M; Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, 06520, USA.; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, 06520, USA.; Department of Computer Science, Yale University, New Haven, CT, 06520, USA.; Department of Statistics & Data Science, Yale University, New Haven, CT, 06520, USA.; Department of Biomedical Informatics & Data Science, Yale University, New Haven, CT, 06520, USA. |
| مؤلفون مشاركون: | PsychENCODE Consortium |
| المصدر: | BioRxiv : the preprint server for biology [bioRxiv] 2024 Mar 30. Date of Electronic Publication: 2024 Mar 30. |
| نوع المنشور: | Preprint |
| اللغة: | English |
| بيانات الدورية: | Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet ISSN: 2692-8205 (Electronic) Linking ISSN: 26928205 NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| مستخلص: | Single-cell genomics is a powerful tool for studying heterogeneous tissues such as the brain. Yet, little is understood about how genetic variants influence cell-level gene expression. Addressing this, we uniformly processed single-nuclei, multi-omics datasets into a resource comprising >2.8M nuclei from the prefrontal cortex across 388 individuals. For 28 cell types, we assessed population-level variation in expression and chromatin across gene families and drug targets. We identified >550K cell-type-specific regulatory elements and >1.4M single-cell expression-quantitative-trait loci, which we used to build cell-type regulatory and cell-to-cell communication networks. These networks manifest cellular changes in aging and neuropsychiatric disorders. We further constructed an integrative model accurately imputing single-cell expression and simulating perturbations; the model prioritized ~250 disease-risk genes and drug targets with associated cell types. Competing Interests: Competing interests Z. Weng (UMass Chan Medical School) co-founded and serves as a scientific advisor for Rgenta Inc. From April 11, 2022, N.L. Jorstad (Allen Institute for Brain Science) has been an employee of Genentech. K.P.W. (National University of Singapore) is a shareholder in Tempus AI and Provaxus Inc. The other authors declare no competing interests. |
| التعليقات: | Update in: Science. 2024 May 24;384(6698):eadi5199. doi: 10.1126/science.adi5199. (PMID: 38781369) |
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| معلومات مُعتمدة: | R01 AG050986 United States AG NIA NIH HHS; R21 MH109956 United States MH NIMH NIH HHS; R01 MH116529 United States MH NIMH NIH HHS; U01 MH103346 United States MH NIMH NIH HHS; R01 AG067025 United States AG NIA NIH HHS; U01 MH116487 United States MH NIMH NIH HHS; R01 MH126393 United States MH NIMH NIH HHS; R01 MH110926 United States MH NIMH NIH HHS; U01 MH116488 United States MH NIMH NIH HHS; R01 MH110928 United States MH NIMH NIH HHS; RF1 MH128970 United States MH NIMH NIH HHS; U01 MH116438 United States MH NIMH NIH HHS; U01 MH116442 United States MH NIMH NIH HHS; R01 MH094714 United States MH NIMH NIH HHS; R01 MH117406 United States MH NIMH NIH HHS; R01 MH109897 United States MH NIMH NIH HHS; U01 MH122591 United States MH NIMH NIH HHS; R21 NS127432 United States NS NINDS NIH HHS; R56 MH114901 United States MH NIMH NIH HHS; R01 MH117292 United States MH NIMH NIH HHS; R21 MH103877 United States MH NIMH NIH HHS; U01 MH114812 United States MH NIMH NIH HHS; U01 MH103365 United States MH NIMH NIH HHS; R01 MH110905 United States MH NIMH NIH HHS; U01 MH122509 United States MH NIMH NIH HHS; U01 MH116489 United States MH NIMH NIH HHS; R01 NS128523 United States NS NINDS NIH HHS; R01 MH110927 United States MH NIMH NIH HHS; U01 MH122678 United States MH NIMH NIH HHS; U01 MH116441 United States MH NIMH NIH HHS; R01 MH121521 United States MH NIMH NIH HHS; U01 MH122849 United States MH NIMH NIH HHS; R56 MH114899 United States MH NIMH NIH HHS; U01 MH103392 United States MH NIMH NIH HHS; R01 MH117291 United States MH NIMH NIH HHS; R21 NS128761 United States NS NINDS NIH HHS; U01 MH122590 United States MH NIMH NIH HHS; R01 MH117293 United States MH NIMH NIH HHS; R01 MH109677 United States MH NIMH NIH HHS; R56 MH114911 United States MH NIMH NIH HHS; R01 MH105472 United States MH NIMH NIH HHS; R01 MH129301 United States MH NIMH NIH HHS; R01 MH111721 United States MH NIMH NIH HHS; P50 HD105353 United States HD NICHD NIH HHS; R01 MH126459 United States MH NIMH NIH HHS; U01 MH103340 United States MH NIMH NIH HHS; U19 AG060909 United States AG NIA NIH HHS; U01 MH103339 United States MH NIMH NIH HHS; I01 BX002395 United States BX BLRD VA; U01 DA048279 United States DA NIDA NIH HHS; R01 MH110920 United States MH NIMH NIH HHS; U01 MH122681 United States MH NIMH NIH HHS; R21 MH102791 United States MH NIMH NIH HHS; R01 MH105898 United States MH NIMH NIH HHS; R21 MH105881 United States MH NIMH NIH HHS; R01 AG065582 United States AG NIA NIH HHS; U01 MH122592 United States MH NIMH NIH HHS; R01 MH125516 United States MH NIMH NIH HHS; R01 MH125246 United States MH NIMH NIH HHS; R01 MH110921 United States MH NIMH NIH HHS; R01 MH123922 United States MH NIMH NIH HHS; R21 MH129817 United States MH NIMH NIH HHS; R21 MH105853 United States MH NIMH NIH HHS; R01 MH109715 United States MH NIMH NIH HHS; R01 HG012572 United States HG NHGRI NIH HHS; RF1 MH128695 United States MH NIMH NIH HHS; U01 MH116492 United States MH NIMH NIH HHS; P50 MH106934 United States MH NIMH NIH HHS |
| تواريخ الأحداث: | Date Created: 20240402 Latest Revision: 20240709 |
| رمز التحديث: | 20240709 |
| مُعرف محوري في PubMed: | PMC10983939 |
| DOI: | 10.1101/2024.03.18.585576 |
| PMID: | 38562822 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2692-8205 |
|---|---|
| DOI: | 10.1101/2024.03.18.585576 |