TY - JOUR
T1 - Host-Viral Infection Maps Reveal Signatures of Severe COVID-19 Patients
AU - Bost, Pierre
AU - Giladi, Amir
AU - Liu, Yang
AU - Bendjelal, Yanis
AU - Xu, Gang
AU - David, Eyal
AU - Blecher-Gonen, Ronnie
AU - Cohen, Merav
AU - Medaglia, Chiara
AU - Li, Hanjie
AU - Deczkowska, Aleksandra
AU - Zhang, Shuye
AU - Schwikowski, Benno
AU - Zhang, Zheng
AU - Amit, Ido
N1 - We thank Dr. Noam Stern Ginossar and Dr. Yoav Golan for careful evaluation of the manuscript; Dr. Etienne Simon-Loriere, Thomas Jacquemont, and Alice Balfourier for valuable advices; Tali Wiesel from the Scientific Illustration unit of the Weizmann Institute for artwork; and members of the Amit laboratory for discussions. I.A. is an Eden and Steven Romick Professorial Chair and supported by Merck KGaA (Darmstadt, Germany), the Chan Zuckerberg Initiative (CZI), an HHMI International Scholar award, the European Research Council Consolidator Grant (ERC-COG) 724471-HemTree2.0, an SCA award from the Wolfson Foundation and Family Charitable Trust, the Thompson Family Foundation, an MRA Established Investigator Award (509044), the Israel Science Foundation (703/15), the Ernest and Bonnie Beutler Research Program for Excellence in Genomic Medicine, the Helen and Martin Kimmel award for innovative investigation, a NeuroMac DFG/Transregional Collaborative Research Center grant, an International Progressive MS Alliance/NMSS (PA-1604 08459), and an Adelis Foundation grant. P.B. is supported by a PhD scholarship from the Ecole Normale Supérieure, Paris. B.S. has received funding from the French Government’s Investissement d’Avenir program, Laboratoire d’Excellence “Integrative Biology of Emerging Infectious Diseases” (ANR-10-LABX-62-IBEID). Z.Z. and Y.L. were supported by fundings from the National Natural Science Foundation of China (91442127 to Z.Z.；81700540 to Y.L.). Author Contributions P.B. designed and developed Viral-Track, performed various computational analyses, and wrote the manuscript. A.G. performed computational analyses and wrote the manuscript. Y.L., G.X., and S.Z. designed and performed experiments. Y.B. developed Viral-Track. E.D. contributed to data processing and analysis. R.B.-G., M.C., and C.M. designed and performed experiments. H.L. contributed to data analysis. A.D. contributed to data analysis, manuscript writing, and scientific communication. B.S. contributed to development of computational methods and bioinformatic analysis and wrote the manuscript. Z.Z. conceived, designed, and analyzed experiments and wrote the manuscript. I.A. directed the project, conceived, designed, and analyzed experiments, and wrote the manuscript.
PY - 2020/6/25
Y1 - 2020/6/25
N2 - Viruses are a constant threat to global health as highlighted by the current COVID-19 pandemic. Currently, lack of data underlying how the human host interacts with viruses, including the SARS-CoV-2 virus, limits effective therapeutic intervention. We introduce Viral-Track, a computational method that globally scans unmapped single-cell RNA sequencing (scRNA-seq) data for the presence of viral RNA, enabling transcriptional cell sorting of infected versus bystander cells. We demonstrate the sensitivity and specificity of Viral-Track to systematically detect viruses from multiple models of infection, including hepatitis B virus, in an unsupervised manner Applying Viral-Track to bronchoalveloar-lavage samples from severe and mild COVID-19 patients reveals a dramatic impact of the virus on the immune system of severe patients compared to mild cases. Viral-Track detects an unexpected co-infection of the human metapneumovirus, present mainly in monocytes perturbed in type-I interferon (IFN)-signaling. Viral-Track provides a robust technology for dissecting the mechanisms of viral-infection and pathology.
AB - Viruses are a constant threat to global health as highlighted by the current COVID-19 pandemic. Currently, lack of data underlying how the human host interacts with viruses, including the SARS-CoV-2 virus, limits effective therapeutic intervention. We introduce Viral-Track, a computational method that globally scans unmapped single-cell RNA sequencing (scRNA-seq) data for the presence of viral RNA, enabling transcriptional cell sorting of infected versus bystander cells. We demonstrate the sensitivity and specificity of Viral-Track to systematically detect viruses from multiple models of infection, including hepatitis B virus, in an unsupervised manner Applying Viral-Track to bronchoalveloar-lavage samples from severe and mild COVID-19 patients reveals a dramatic impact of the virus on the immune system of severe patients compared to mild cases. Viral-Track detects an unexpected co-infection of the human metapneumovirus, present mainly in monocytes perturbed in type-I interferon (IFN)-signaling. Viral-Track provides a robust technology for dissecting the mechanisms of viral-infection and pathology.
UR - http://www.scopus.com/inward/record.url?scp=85085276687&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2020.05.006
DO - 10.1016/j.cell.2020.05.006
M3 - مقالة
SN - 0092-8674
VL - 181
SP - 1475
EP - 1488
JO - Cell
JF - Cell
IS - 7
ER -