Shotgun transcriptome, spatial omics, and isothermal profiling of SARS-CoV-2 infection reveals unique host responses, viral diversification, and drug interactions.
| Title: | Shotgun transcriptome, spatial omics, and isothermal profiling of SARS-CoV-2 infection reveals unique host responses, viral diversification, and drug interactions. |
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| Authors: | Butler D; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA.; Mozsary C; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA.; Meydan C; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA.; The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA.; WorldQuant Initiative for Quantitative Prediction, Weill Cornell Medicine, New York, NY, USA.; Foox J; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA.; The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA.; Rosiene J; New York Genome Center, New York, NY, USA.; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.; Shaiber A; New York Genome Center, New York, NY, USA.; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.; Englander Institute for Precision Medicine and the Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.; Danko D; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA.; Afshinnekoo E; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA.; The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA.; WorldQuant Initiative for Quantitative Prediction, Weill Cornell Medicine, New York, NY, USA.; MacKay M; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA.; Sedlazeck FJ; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.; Ivanov NA; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA.; The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA.; Clinical & Translational Science Center, Weill Cornell Medicine, New York, NY, USA.; Sierra M; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA.; The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA.; Pohle D; Institute of Medical Virology and Epidemiology of Viral Diseases, University Hospital Tuebingen, Tuebingen, Germany.; Zietz M; Department of Biomedical Informatics, Department of Systems Biology, Department of Medicine, Institute for Genomic Medicine, Columbia University, Columbia, NY, USA.; Gisladottir U; Department of Biomedical Informatics, Department of Systems Biology, Department of Medicine, Institute for Genomic Medicine, Columbia University, Columbia, NY, USA.; Ramlall V; Department of Biomedical Informatics, Department of Systems Biology, Department of Medicine, Institute for Genomic Medicine, Columbia University, Columbia, NY, USA.; Department of Cellular, Molecular Physiology & Biophysics, Columbia University, Columbia, NY, USA.; Sholle ET; Information Technologies & Services Department, Weill Cornell Medicine, New York, NY, USA.; Schenck EJ; Department of Medicine, Weill Cornell Medicine, New York, NY, USA.; Westover CD; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA.; Hassan C; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA.; Ryon K; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA.; Young B; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA.; Bhattacharya C; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA.; Ng DL; Department of Laboratory Medicine, University of California, San Francisco, CA, USA.; Granados AC; Department of Laboratory Medicine, University of California, San Francisco, CA, USA.; UCSF-Abbott Viral Diagnostics and Discovery Center, San Francisco, CA, USA.; Santos YA; Department of Laboratory Medicine, University of California, San Francisco, CA, USA.; UCSF-Abbott Viral Diagnostics and Discovery Center, San Francisco, CA, USA.; Servellita V; Department of Laboratory Medicine, University of California, San Francisco, CA, USA.; UCSF-Abbott Viral Diagnostics and Discovery Center, San Francisco, CA, USA.; Federman S; Department of Laboratory Medicine, University of California, San Francisco, CA, USA.; UCSF-Abbott Viral Diagnostics and Discovery Center, San Francisco, CA, USA.; Ruggiero P; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.; Fungtammasan A; DNAnexus, Inc., Mountain View, CA, USA.; Chin CS; DNAnexus, Inc., Mountain View, CA, USA.; Pearson NM; Root Deep Insight, Boston, MA, USA.; Langhorst BW; New England Biolabs, Ipswich, MA, USA.; Tanner NA; New England Biolabs, Ipswich, MA, USA.; Kim Y; NanoString Technologies, Seattle, WA, USA.; Reeves JW; NanoString Technologies, Seattle, WA, USA.; Hether TD; NanoString Technologies, Seattle, WA, USA.; Warren SE; NanoString Technologies, Seattle, WA, USA.; Bailey M; NanoString Technologies, Seattle, WA, USA.; Gawrys J; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.; Meleshko D; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA.; Tri-Institutional Computational Biology & Medicine Program, Weill Cornell Medicine, New York, NY, USA.; Xu D; Genomics Resources Core Facility, Weill Cornell Medicine, New York, NY, USA.; Couto-Rodriguez M; Biotia, Inc., New York, NY, USA.; Nagy-Szakal D; Biotia, Inc., New York, NY, USA.; Department of Cell Biology, SUNY Downstate Health Sciences University, New York, NY, USA.; Barrows J; Biotia, Inc., New York, NY, USA.; Wells H; Biotia, Inc., New York, NY, USA.; O'Hara NB; Biotia, Inc., New York, NY, USA.; Department of Cell Biology, SUNY Downstate Health Sciences University, New York, NY, USA.; Rosenfeld JA; Rutgers Cancer Institute of New Jersey, New York, NJ, USA.; Department of Pathology, Robert Wood Johnson Medical School, New York, NJ, USA.; Chen Y; Rutgers Cancer Institute of New Jersey, New York, NJ, USA.; Steel PAD; Department of Emergency Medicine, Weill Cornell Medicine, New York, NY, USA.; Shemesh AJ; Department of Emergency Medicine, Weill Cornell Medicine, New York, NY, USA.; Xiang J; Genomics Resources Core Facility, Weill Cornell Medicine, New York, NY, USA.; Thierry-Mieg J; National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA.; Thierry-Mieg D; National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA.; Iftner A; Institute of Medical Virology and Epidemiology of Viral Diseases, University Hospital Tuebingen, Tuebingen, Germany.; Bezdan D; Institute of Medical Virology and Epidemiology of Viral Diseases, University Hospital Tuebingen, Tuebingen, Germany.; Sanchez E; Department of Medicine, Weill Cornell Medicine, New York, NY, USA.; Campion TR Jr; Information Technologies & Services Department, Weill Cornell Medicine, New York, NY, USA.; Department of Population Health Sciences, Weill Cornell Medicine, New York, NY, USA.; Sipley J; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.; Cong L; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.; Craney A; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.; Velu P; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.; Melnick AM; Department of Medicine, Weill Cornell Medicine, New York, NY, USA.; Shapira S; Department of Biomedical Informatics, Department of Systems Biology, Department of Medicine, Institute for Genomic Medicine, Columbia University, Columbia, NY, USA.; Hajirasouliha I; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA.; The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA.; Englander Institute for Precision Medicine and the Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.; Borczuk A; Department of Medicine, Weill Cornell Medicine, New York, NY, USA.; Iftner T; Institute of Medical Virology and Epidemiology of Viral Diseases, University Hospital Tuebingen, Tuebingen, Germany.; Salvatore M; Department of Medicine, Weill Cornell Medicine, New York, NY, USA.; Department of Population Health Sciences, Weill Cornell Medicine, New York, NY, USA.; Loda M; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.; Westblade LF; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.; Department of Medicine, Weill Cornell Medicine, New York, NY, USA.; Cushing M; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.; Wu S; Hangzhou Cancer Institute, Hangzhou Cancer Hospital, Hangzhou, China.; Department of Radiation Oncology, Hangzhou Cancer Hospital, Hangzhou, China.; Levy S; HudsonAlpha Discovery Institute, Huntsville, AL, USA.; Chiu C; Department of Laboratory Medicine, University of California, San Francisco, CA, USA.; UCSF-Abbott Viral Diagnostics and Discovery Center, San Francisco, CA, USA.; Department of Medicine, Division of Infectious Diseases, University of California, San Francisco, CA, USA.; Schwartz RE; Department of Medicine, Weill Cornell Medicine, New York, NY, USA. res2025@med.cornell.edu.; Tatonetti N; Department of Biomedical Informatics, Department of Systems Biology, Department of Medicine, Institute for Genomic Medicine, Columbia University, Columbia, NY, USA. npt2105@cumc.columbia.edu.; Rennert H; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA. har2006@med.cornell.edu.; Imielinski M; New York Genome Center, New York, NY, USA. mai9037@med.cornell.edu.; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA. mai9037@med.cornell.edu.; Englander Institute for Precision Medicine and the Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA. mai9037@med.cornell.edu.; Mason CE; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA. chm2042@med.cornell.edu.; The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA. chm2042@med.cornell.edu.; WorldQuant Initiative for Quantitative Prediction, Weill Cornell Medicine, New York, NY, USA. chm2042@med.cornell.edu.; The Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA. chm2042@med.cornell.edu. |
| Source: | Nature communications [Nat Commun] 2021 Mar 12; Vol. 12 (1), pp. 1660. Date of Electronic Publication: 2021 Mar 12. |
| Publication Type: | Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
| Language: | English |
| Journal Info: | Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [London] : Nature Pub. Group |
| MeSH Terms: | COVID-19/*genetics ; COVID-19/*virology ; SARS-CoV-2/*genetics; Angiotensin Receptor Antagonists/pharmacology ; Angiotensin-Converting Enzyme Inhibitors/pharmacology ; Antiviral Agents/pharmacology ; COVID-19/epidemiology ; HLA Antigens/genetics ; Host Microbial Interactions/drug effects ; Host Microbial Interactions/genetics ; New York City/epidemiology ; SARS-CoV-2/classification ; SARS-CoV-2/drug effects ; Adult ; Aged ; COVID-19 Nucleic Acid Testing ; Drug Interactions ; Female ; Gene Expression Profiling ; Genome, Viral ; Humans ; Male ; Middle Aged ; Molecular Diagnostic Techniques ; Nucleic Acid Amplification Techniques ; Pandemics ; RNA-Seq ; COVID-19 Drug Treatment |
| Abstract: | In less than nine months, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) killed over a million people, including >25,000 in New York City (NYC) alone. The COVID-19 pandemic caused by SARS-CoV-2 highlights clinical needs to detect infection, track strain evolution, and identify biomarkers of disease course. To address these challenges, we designed a fast (30-minute) colorimetric test (LAMP) for SARS-CoV-2 infection from naso/oropharyngeal swabs and a large-scale shotgun metatranscriptomics platform (total-RNA-seq) for host, viral, and microbial profiling. We applied these methods to clinical specimens gathered from 669 patients in New York City during the first two months of the outbreak, yielding a broad molecular portrait of the emerging COVID-19 disease. We find significant enrichment of a NYC-distinctive clade of the virus (20C), as well as host responses in interferon, ACE, hematological, and olfaction pathways. In addition, we use 50,821 patient records to find that renin-angiotensin-aldosterone system inhibitors have a protective effect for severe COVID-19 outcomes, unlike similar drugs. Finally, spatial transcriptomic data from COVID-19 patient autopsy tissues reveal distinct ACE2 expression loci, with macrophage and neutrophil infiltration in the lungs. These findings can inform public health and may help develop and drive SARS-CoV-2 diagnostic, prevention, and treatment strategies. |
| Comments: | Update of: bioRxiv. 2020 May 01:2020.04.20.048066. doi: 10.1101/2020.04.20.048066.. (PMID: 32511352) |
| References: | Bioinformatics. 2012 Sep 15;28(18):i333-i339. (PMID: 22962449); Biostatistics. 2007 Jan;8(1):118-27. (PMID: 16632515); Nat Biotechnol. 2020 Mar;38(3):276-278. (PMID: 32055031); Nat Commun. 2020 Oct 12;11(1):5139. (PMID: 33046696); Nat Biotechnol. 2015 Mar;33(3):290-5. (PMID: 25690850); Lancet Infect Dis. 2020 May;20(5):533-534. (PMID: 32087114); Cell. 2020 May 28;181(5):990-996.e5. (PMID: 32386545); Lancet Infect Dis. 2020 May;20(5):515-516. (PMID: 32213336); Bioinformatics. 2012 Mar 15;28(6):882-3. (PMID: 22257669); Bioinformatics. 2012 Aug 15;28(16):2184-5. (PMID: 22743226); Chest. 2007 Aug;132(2):410-7. (PMID: 17573487); Bioinformatics. 2014 Apr 1;30(7):923-30. (PMID: 24227677); Bull World Health Organ. 2020 Jul 01;98(7):495-504. (PMID: 32742035); Mol Biol Evol. 2013 Apr;30(4):772-80. (PMID: 23329690); J Med Virol. 2020 Jul;92(7):719-725. (PMID: 32170865); Nat Med. 2020 Jul;26(7):1033-1036. (PMID: 32398876); Virus Evol. 2018 Jan 08;4(1):vex042. (PMID: 29340210); Sci Immunol. 2020 Jul 10;5(49):. (PMID: 32651212); Clin Chim Acta. 2020 Jun;505:172-175. (PMID: 32156607); Bioinformatics. 2020 Jan 1;36(1):33-40. (PMID: 31173059); Genome Biol. 2014;15(12):550. (PMID: 25516281); Bioinformatics. 2011 Jun 15;27(12):1739-40. (PMID: 21546393); Bioinformatics. 2016 Jan 15;32(2):292-4. (PMID: 26428292); Nat Med. 2020 Jun;26(6):845-848. (PMID: 32350462); Clin Chem. 2020 Jul 1;66(7):975-977. (PMID: 32315390); Science. 2020 Jul 17;369(6501):297-301. (PMID: 32471856); Bioinformatics. 2014 Feb 15;30(4):523-30. (PMID: 24336805); Virus Res. 2015 Apr 16;202:89-100. (PMID: 25432065); Gigascience. 2022 Dec 28;12:. (PMID: 36644891); J Infect. 2020 Aug;81(2):266-275. (PMID: 32473235); Biochim Biophys Acta. 2006 Jul;1763(7):723-36. (PMID: 16839620); Nat Commun. 2019 Feb 4;10(1):579. (PMID: 30718479); Science. 2020 May 1;368(6490):489-493. (PMID: 32179701); Genome Biol. 2014 Jun 26;15(6):R84. (PMID: 24970577); Cell Rep. 2018 Nov 20;25(8):2223-2233.e6. (PMID: 30463017); Hypertens Res. 2006 Nov;29(11):865-74. (PMID: 17345786); Nat Microbiol. 2020 Mar;5(3):443-454. (PMID: 31932713); PLoS One. 2012;7(1):e29870. (PMID: 22272257); Bioinformatics. 2016 Apr 15;32(8):1220-2. (PMID: 26647377); Nat Biotechnol. 2020 Sep;38(9):1021-1024. (PMID: 32820257); Genome Biol. 2010;11(3):R25. (PMID: 20196867); Bioinformatics. 2018 Dec 1;34(23):4121-4123. (PMID: 29790939); Euro Surveill. 2017 Mar 30;22(13):. (PMID: 28382917); BMC Bioinformatics. 2011 Mar 17;12:77. (PMID: 21414208); Bioinformatics. 2016 Oct 1;32(19):3047-8. (PMID: 27312411); Bioinformatics. 2010 Jan 1;26(1):139-40. (PMID: 19910308); Signal Transduct Target Ther. 2020 May 29;5(1):84. (PMID: 32467561); Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50. (PMID: 16199517); N Engl J Med. 2017 Aug 3;377(5):419-430. (PMID: 28528561); Nat Commun. 2019 Jan 22;10(1):380. (PMID: 30670690); Genome Biol. 2014 Feb 03;15(2):R29. (PMID: 24485249); Nat Methods. 2012 Mar 04;9(4):357-9. (PMID: 22388286); Nat Commun. 2017 Jan 24;8:14061. (PMID: 28117401); Natl Sci Rev. 2020 Jun;7(6):1012-1023. (PMID: 34676127); J Clin Virol. 2020 Mar;124:104262. (PMID: 32007841); Curr Protoc Bioinformatics. 2015 Sep 03;51:11.14.1-11.14.19. (PMID: 26334920); BMC Bioinformatics. 2016 Oct 21;17(1):428. (PMID: 27769170); EMBO J. 2020 May 18;39(10):e105114. (PMID: 32246845); Circulation. 2005 May 24;111(20):2605-10. (PMID: 15897343); Bioinformatics. 1998;14(4):380-1. (PMID: 9632837); Nat Biotechnol. 2011 Jan;29(1):24-6. (PMID: 21221095); F1000Res. 2018 Aug 24;7:1338. (PMID: 30254741); Nature. 2020 Aug;584(7821):463-469. (PMID: 32717743); Ann Intern Med. 2020 May 05;172(9):577-582. (PMID: 32150748); Nucleic Acids Res. 2016 Jul 8;44(W1):W90-7. (PMID: 27141961); JAMA. 2020 May 12;323(18):1769-1770. (PMID: 32208485); Cell. 2020 May 28;181(5):1036-1045.e9. (PMID: 32416070); Nat Methods. 2015 Oct;12(10):966-8. (PMID: 26258291); Glob Chall. 2017 Jan 10;1(1):33-46. (PMID: 31565258); Nucleic Acids Res. 2018 Jan 4;46(D1):D836-D842. (PMID: 29092072); Lancet Respir Med. 2020 Apr;8(4):e21. (PMID: 32171062); FASEB J. 2019 Aug;33(8):8865-8877. (PMID: 31034780); Intensive Care Med. 1996 Jul;22(7):707-10. (PMID: 8844239); Bioinformatics. 2009 Aug 15;25(16):2078-9. (PMID: 19505943); Genome Biol. 2019 Jan 8;20(1):8. (PMID: 30621750); Euro Surveill. 2020 Feb;25(5):. (PMID: 32046816); Cell. 2020 Apr 16;181(2):271-280.e8. (PMID: 32142651); Nucleic Acids Res. 2016 Jan 4;44(D1):D733-45. (PMID: 26553804); Euro Surveill. 2020 Mar;25(9):. (PMID: 32156330); Cell. 2020 May 14;181(4):905-913.e7. (PMID: 32333836); Genome Biol. 2019 Nov 28;20(1):257. (PMID: 31779668); Cell. 2020 May 28;181(5):997-1003.e9. (PMID: 32359424); Nat Med. 2020 May;26(5):681-687. (PMID: 32327758); Circ Res. 2020 Jun 5;126(12):1671-1681. (PMID: 32302265); Immunity. 2019 May 21;50(5):1317-1334.e10. (PMID: 30979687); Genome Res. 2014 Jul;24(7):1180-92. (PMID: 24899342); Gut Pathog. 2017 Jan 3;9:1. (PMID: 28053669) |
| Grant Information: | T15 LM007079 United States LM NLM NIH HHS; TL1 TR002386 United States TR NCATS NIH HHS; U19 AI144297 United States AI NIAID NIH HHS; R35 GM138152 United States GM NIGMS NIH HHS; UL1 TR002384 United States TR NCATS NIH HHS; R01 DK121072 United States DK NIDDK NIH HHS; R35 GM131905 United States GM NIGMS NIH HHS; UL1 TR000457 United States TR NCATS NIH HHS; U01 DA053941 United States DA NIDA NIH HHS; R01 MH117406 United States MH NIMH NIH HHS; R25 EB020393 United States EB NIBIB NIH HHS; R01 AI151059 United States AI NIAID NIH HHS |
| Substance Nomenclature: | 0 (Angiotensin Receptor Antagonists); 0 (Angiotensin-Converting Enzyme Inhibitors); 0 (Antiviral Agents); 0 (HLA Antigens) |
| SCR Protocol: | LAMP assay |
| Entry Date(s): | Date Created: 20210313 Date Completed: 20210322 Latest Revision: 20240923 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC7954844 |
| DOI: | 10.1038/s41467-021-21361-7 |
| PMID: | 33712587 |
| Database: | MEDLINE |
Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.