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BIOLOGICAL SCIENCES / APPLIED BIOLOGICAL SCIENCES
Severe acute respiratory syndrome diagnostics using a coronavirus protein microarray

Heng Zhu^*,,,, Shaohui Hu^,, Ghil Jona^*,, Xiaowei Zhu^,¶, Nate Kreiswirth^||, Barbara M. Willey^||, Tony Mazzulli^||, Guozhen Liu^,**, Qifeng Song, Peng Chen, Mark Cameron^||, Andrea Tyler^||, Jian Wang, Jie Wen, Weijun Chen, Susan Compton, and Michael Snyder^*,¶,

Departments of *Molecular, Cellular, and Developmental Biology and Comparative Medicine, and ^¶Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520; Biochip Platform Division, Beijing Genomics Institute, Chinese Academy of Sciences, Beijing 101300, China; ^||Department of Microbiology, Mount Sinai Hospital, Toronto, ON, Canada M5G 1X5; and **College of Life Sciences, Agricultural University of Hebei, Hebei, Baoding 071001, China

Communicated by Dieter Söll, Yale University, New Haven, CT, January 16, 2006 (received for review October 10, 2005)

To monitor severe acute respiratory syndrome (SARS) infection, a coronavirus protein microarray that harbors proteins from SARS coronavirus (SARS-CoV) and five additional coronaviruses was constructed. These microarrays were used to screen 400 Canadian sera from the SARS outbreak, including samples from confirmed SARS-CoV cases, respiratory illness patients, and healthcare professionals. A computer algorithm that uses multiple classifiers to predict samples from SARS patients was developed and used to predict 206 sera from Chinese fever patients. The test assigned patients into two distinct groups: those with antibodies to SARS-CoV and those without. The microarray also identified patients with sera reactive against other coronavirus proteins. Our results correlated well with an indirect immunofluorescence test and demonstrated that viral infection can be monitored for many months after infection. We show that protein microarrays can serve as a rapid, sensitive, and simple tool for large-scale identification of viral-specific antibodies in sera.

infectious disease | protein chip | virus diagnostics

Present address: Department of Pharmacology and Molecular Sciences and the HiT Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205.

Author contributions: H.Z., S.H., G.J., B.M.W., and M.S. designed research; H.Z., S.H., G.J., N.K., B.M.W., and T.M. performed research; H.Z., S.H., G.J., X.Z., N.K., B.M.W., T.M., G.L., Q.S., P.C., M.C., A.T., J. Wang, J. Wen, W.C., S.C., and M.S. contributed new reagents/analytic tools; X.Z., M.S., and G.J. analyzed data; and H.Z., G.J., X.Z., B.M.W., and M.S. wrote the paper.

Conflict of interest statement: M.S. consults for Invitrogen.

To whom correspondence should be addressed. E-mail: michael.snyder{at}yale.edu

© 2006 by The National Academy of Sciences of the USA

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