Molecular signature of clinical severity in recovering patients with severe acute respiratory syndrome coronavirus (SARS-CoV)
Identifieur interne : 001171 ( Ncbi/Merge ); précédent : 001170; suivant : 001172Molecular signature of clinical severity in recovering patients with severe acute respiratory syndrome coronavirus (SARS-CoV)
Auteurs : Yun-Shien Lee [Taïwan] ; Chun-Houh Chen [Taïwan] ; Angel Chao [Taïwan] ; En-Shih Chen [Taïwan] ; Min-Li Wei [Taïwan] ; Lung-Kun Chen [Taïwan] ; Kuender D. Yang [Taïwan] ; Meng-Chih Lin [Taïwan] ; Yi-Hsi Wang [Taïwan] ; Jien-Wei Liu [Taïwan] ; Hock-Liew Eng [Taïwan] ; Ping-Cherng Chiang [Taïwan] ; Ting-Shu Wu [Taïwan] ; Kuo-Chein Tsao [Taïwan] ; Chung-Guei Huang [Taïwan] ; Yin-Jing Tien [Taïwan] ; Tzu-Hao Wang [Taïwan] ; Hsing-Shih Wang [Taïwan] ; Ying-Shiung Lee [Taïwan]Source :
- BMC Genomics [ 1471-2164 ] ; 2005.
Descripteurs français
- KwdFr :
- ADN complémentaire (métabolisme), Algorithmes, Analyse de regroupements, Biologie informatique, Expression des gènes, Gènes viraux, Génome, Humains, Immunité innée, Maladies pulmonaires (métabolisme), Maladies pulmonaires (virologie), Modèles génétiques, Modèles statistiques, RT-PCR, Régulation de l'expression des gènes viraux, Régulation positive, Syndrome respiratoire aigu sévère (sang), Syndrome respiratoire aigu sévère (virologie), Séquençage par oligonucléotides en batterie, Test ELISA, Virus du SRAS (génétique).
- MESH :
- génétique : Virus du SRAS.
- métabolisme : ADN complémentaire, Maladies pulmonaires.
- sang : Syndrome respiratoire aigu sévère.
- virologie : Maladies pulmonaires, Syndrome respiratoire aigu sévère.
- Algorithmes, Analyse de regroupements, Biologie informatique, Expression des gènes, Gènes viraux, Génome, Humains, Immunité innée, Modèles génétiques, Modèles statistiques, RT-PCR, Régulation de l'expression des gènes viraux, Régulation positive, Séquençage par oligonucléotides en batterie, Test ELISA.
English descriptors
- KwdEn :
- Algorithms, Cluster Analysis, Computational Biology, DNA, Complementary (metabolism), Enzyme-Linked Immunosorbent Assay, Gene Expression, Gene Expression Regulation, Viral, Genes, Viral, Genome, Humans, Immunity, Innate, Lung Diseases (metabolism), Lung Diseases (virology), Models, Genetic, Models, Statistical, Oligonucleotide Array Sequence Analysis, Reverse Transcriptase Polymerase Chain Reaction, SARS Virus (genetics), Severe Acute Respiratory Syndrome (blood), Severe Acute Respiratory Syndrome (virology), Up-Regulation.
- MESH :
- chemical , metabolism : DNA, Complementary.
- blood : Severe Acute Respiratory Syndrome.
- genetics : SARS Virus.
- metabolism : Lung Diseases.
- virology : Lung Diseases, Severe Acute Respiratory Syndrome.
- Algorithms, Cluster Analysis, Computational Biology, Enzyme-Linked Immunosorbent Assay, Gene Expression, Gene Expression Regulation, Viral, Genes, Viral, Genome, Humans, Immunity, Innate, Models, Genetic, Models, Statistical, Oligonucleotide Array Sequence Analysis, Reverse Transcriptase Polymerase Chain Reaction, Up-Regulation.
Abstract
Severe acute respiratory syndrome (SARS), a recent epidemic human disease, is caused by a novel coronavirus (SARS-CoV). First reported in Asia, SARS quickly spread worldwide through international travelling. As of July 2003, the World Health Organization reported a total of 8,437 people afflicted with SARS with a 9.6% mortality rate. Although immunopathological damages may account for the severity of respiratory distress, little is known about how the genome-wide gene expression of the host changes under the attack of SARS-CoV.
Based on changes in gene expression of peripheral blood, we identified 52 signature genes that accurately discriminated acute SARS patients from non-SARS controls. While a general suppression of gene expression predominated in SARS-infected blood, several genes including those involved in innate immunity, such as defensins and eosinophil-derived neurotoxin, were upregulated. Instead of employing clustering methods, we ranked the severity of recovering SARS patients by generalized associate plots (GAP) according to the expression profiles of 52 signature genes. Through this method, we discovered a smooth transition pattern of severity from normal controls to acute SARS patients. The rank of SARS severity was significantly correlated with the recovery period (in days) and with the clinical pulmonary infection score.
The use of the GAP approach has proved useful in analyzing the complexity and continuity of biological systems. The severity rank derived from the global expression profile of significantly regulated genes in patients may be useful for further elucidating the pathophysiology of their disease.
The online version of this article (doi:10.1186/1471-2164-6-132) contains supplementary material, which is available to authorized users.
Url:
DOI: 10.1186/1471-2164-6-132
PubMed: 16174304
PubMed Central: 1262710
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PMC:1262710Le document en format XML
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<author><name sortKey="Wei, Min Li" sort="Wei, Min Li" uniqKey="Wei M" first="Min-Li" last="Wei">Min-Li Wei</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1">Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital (CGMH), Tao-Yuan, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital (CGMH), Tao-Yuan</wicri:regionArea>
<wicri:noRegion>Tao-Yuan</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Chen, Lung Kun" sort="Chen, Lung Kun" uniqKey="Chen L" first="Lung-Kun" last="Chen">Lung-Kun Chen</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1">Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital (CGMH), Tao-Yuan, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital (CGMH), Tao-Yuan</wicri:regionArea>
<wicri:noRegion>Tao-Yuan</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Yang, Kuender D" sort="Yang, Kuender D" uniqKey="Yang K" first="Kuender D" last="Yang">Kuender D. Yang</name>
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<institution-id institution-id-type="ISNI">0000000406209374</institution-id>
<institution>Department of Pediatrics,</institution>
<institution>Kaohsiung Medical Center, CGMH,</institution>
</institution-wrap>
Kaohsiung, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Kaohsiung</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Lin, Meng Chih" sort="Lin, Meng Chih" uniqKey="Lin M" first="Meng-Chih" last="Lin">Meng-Chih Lin</name>
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<institution-id institution-id-type="ISNI">0000000406209374</institution-id>
<institution>Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine,</institution>
<institution>Kaohsiung Medical Center, CGMH,</institution>
</institution-wrap>
Kaohsiung, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Kaohsiung</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Wang, Yi Hsi" sort="Wang, Yi Hsi" uniqKey="Wang Y" first="Yi-Hsi" last="Wang">Yi-Hsi Wang</name>
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<institution-id institution-id-type="ISNI">0000000406209374</institution-id>
<institution>Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine,</institution>
<institution>Kaohsiung Medical Center, CGMH,</institution>
</institution-wrap>
Kaohsiung, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Kaohsiung</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Liu, Jien Wei" sort="Liu, Jien Wei" uniqKey="Liu J" first="Jien-Wei" last="Liu">Jien-Wei Liu</name>
<affiliation wicri:level="1"><nlm:aff id="Aff8"><institution-wrap><institution-id institution-id-type="GRID">grid.412027.2</institution-id>
<institution-id institution-id-type="ISNI">0000000406209374</institution-id>
<institution>Department of Internal Medicine, Division of Infectious Diseases,</institution>
<institution>Kaohsiung Medical Center, CGMH,</institution>
</institution-wrap>
Kaohsiung, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Kaohsiung</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Eng, Hock Liew" sort="Eng, Hock Liew" uniqKey="Eng H" first="Hock-Liew" last="Eng">Hock-Liew Eng</name>
<affiliation wicri:level="1"><nlm:aff id="Aff9"><institution-wrap><institution-id institution-id-type="GRID">grid.412027.2</institution-id>
<institution-id institution-id-type="ISNI">0000000406209374</institution-id>
<institution>Department of Pathology,</institution>
<institution>Kaohsiung Medical Center, CGMH,</institution>
</institution-wrap>
Kaohsiung, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Kaohsiung</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Chiang, Ping Cherng" sort="Chiang, Ping Cherng" uniqKey="Chiang P" first="Ping-Cherng" last="Chiang">Ping-Cherng Chiang</name>
<affiliation wicri:level="1"><nlm:aff id="Aff10"><institution-wrap><institution-id institution-id-type="GRID">grid.454211.7</institution-id>
<institution-id institution-id-type="ISNI">000000041756999X</institution-id>
<institution>Department of Internal Medicine, Division of Infectious Diseases,</institution>
<institution>Lin-Kou Medical Center, CGMH,</institution>
</institution-wrap>
Tao-Yuan, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Tao-Yuan</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Wu, Ting Shu" sort="Wu, Ting Shu" uniqKey="Wu T" first="Ting-Shu" last="Wu">Ting-Shu Wu</name>
<affiliation wicri:level="1"><nlm:aff id="Aff10"><institution-wrap><institution-id institution-id-type="GRID">grid.454211.7</institution-id>
<institution-id institution-id-type="ISNI">000000041756999X</institution-id>
<institution>Department of Internal Medicine, Division of Infectious Diseases,</institution>
<institution>Lin-Kou Medical Center, CGMH,</institution>
</institution-wrap>
Tao-Yuan, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Tao-Yuan</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Tsao, Kuo Chein" sort="Tsao, Kuo Chein" uniqKey="Tsao K" first="Kuo-Chein" last="Tsao">Kuo-Chein Tsao</name>
<affiliation wicri:level="1"><nlm:aff id="Aff11">Clinical Virology Laboratory, Department of Clinical Pathology, CGMH, Tao-Yuan, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Clinical Virology Laboratory, Department of Clinical Pathology, CGMH, Tao-Yuan</wicri:regionArea>
<wicri:noRegion>Tao-Yuan</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Huang, Chung Guei" sort="Huang, Chung Guei" uniqKey="Huang C" first="Chung-Guei" last="Huang">Chung-Guei Huang</name>
<affiliation wicri:level="1"><nlm:aff id="Aff11">Clinical Virology Laboratory, Department of Clinical Pathology, CGMH, Tao-Yuan, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Clinical Virology Laboratory, Department of Clinical Pathology, CGMH, Tao-Yuan</wicri:regionArea>
<wicri:noRegion>Tao-Yuan</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Tien, Yin Jing" sort="Tien, Yin Jing" uniqKey="Tien Y" first="Yin-Jing" last="Tien">Yin-Jing Tien</name>
<affiliation wicri:level="1"><nlm:aff id="Aff12"><institution-wrap><institution-id institution-id-type="GRID">grid.37589.30</institution-id>
<institution-id institution-id-type="ISNI">0000000405323167</institution-id>
<institution>Institute of Statistics,</institution>
<institution>National Central University,</institution>
</institution-wrap>
Tao-Yuan, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Tao-Yuan</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Wang, Tzu Hao" sort="Wang, Tzu Hao" uniqKey="Wang T" first="Tzu-Hao" last="Wang">Tzu-Hao Wang</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1">Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital (CGMH), Tao-Yuan, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital (CGMH), Tao-Yuan</wicri:regionArea>
<wicri:noRegion>Tao-Yuan</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.454211.7</institution-id>
<institution-id institution-id-type="ISNI">000000041756999X</institution-id>
<institution>Department of Obstetrics and Gynecology,</institution>
<institution>Lin-Kou Medical Center, CGMH,</institution>
</institution-wrap>
Tao-Yuan, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Tao-Yuan</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Wang, Hsing Shih" sort="Wang, Hsing Shih" uniqKey="Wang H" first="Hsing-Shih" last="Wang">Hsing-Shih Wang</name>
<affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.454211.7</institution-id>
<institution-id institution-id-type="ISNI">000000041756999X</institution-id>
<institution>Department of Obstetrics and Gynecology,</institution>
<institution>Lin-Kou Medical Center, CGMH,</institution>
</institution-wrap>
Tao-Yuan, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Tao-Yuan</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="GRID">grid.145695.a</institution-id>
<institution>Graduate Institute of Clinical Medical Sciences, College of Medicine,</institution>
<institution>Chang Gung University,</institution>
</institution-wrap>
Tao-Yuan, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Tao-Yuan</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Lee, Ying Shiung" sort="Lee, Ying Shiung" uniqKey="Lee Y" first="Ying-Shiung" last="Lee">Ying-Shiung Lee</name>
<affiliation wicri:level="1"><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="GRID">grid.145695.a</institution-id>
<institution>Graduate Institute of Clinical Medical Sciences, College of Medicine,</institution>
<institution>Chang Gung University,</institution>
</institution-wrap>
Tao-Yuan, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Tao-Yuan</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series><title level="j">BMC Genomics</title>
<idno type="eISSN">1471-2164</idno>
<imprint><date when="2005">2005</date>
</imprint>
</series>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Algorithms</term>
<term>Cluster Analysis</term>
<term>Computational Biology</term>
<term>DNA, Complementary (metabolism)</term>
<term>Enzyme-Linked Immunosorbent Assay</term>
<term>Gene Expression</term>
<term>Gene Expression Regulation, Viral</term>
<term>Genes, Viral</term>
<term>Genome</term>
<term>Humans</term>
<term>Immunity, Innate</term>
<term>Lung Diseases (metabolism)</term>
<term>Lung Diseases (virology)</term>
<term>Models, Genetic</term>
<term>Models, Statistical</term>
<term>Oligonucleotide Array Sequence Analysis</term>
<term>Reverse Transcriptase Polymerase Chain Reaction</term>
<term>SARS Virus (genetics)</term>
<term>Severe Acute Respiratory Syndrome (blood)</term>
<term>Severe Acute Respiratory Syndrome (virology)</term>
<term>Up-Regulation</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>ADN complémentaire (métabolisme)</term>
<term>Algorithmes</term>
<term>Analyse de regroupements</term>
<term>Biologie informatique</term>
<term>Expression des gènes</term>
<term>Gènes viraux</term>
<term>Génome</term>
<term>Humains</term>
<term>Immunité innée</term>
<term>Maladies pulmonaires (métabolisme)</term>
<term>Maladies pulmonaires (virologie)</term>
<term>Modèles génétiques</term>
<term>Modèles statistiques</term>
<term>RT-PCR</term>
<term>Régulation de l'expression des gènes viraux</term>
<term>Régulation positive</term>
<term>Syndrome respiratoire aigu sévère (sang)</term>
<term>Syndrome respiratoire aigu sévère (virologie)</term>
<term>Séquençage par oligonucléotides en batterie</term>
<term>Test ELISA</term>
<term>Virus du SRAS (génétique)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>DNA, Complementary</term>
</keywords>
<keywords scheme="MESH" qualifier="blood" xml:lang="en"><term>Severe Acute Respiratory Syndrome</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>SARS Virus</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Virus du SRAS</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Lung Diseases</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>ADN complémentaire</term>
<term>Maladies pulmonaires</term>
</keywords>
<keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>Syndrome respiratoire aigu sévère</term>
</keywords>
<keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Maladies pulmonaires</term>
<term>Syndrome respiratoire aigu sévère</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Lung Diseases</term>
<term>Severe Acute Respiratory Syndrome</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Algorithms</term>
<term>Cluster Analysis</term>
<term>Computational Biology</term>
<term>Enzyme-Linked Immunosorbent Assay</term>
<term>Gene Expression</term>
<term>Gene Expression Regulation, Viral</term>
<term>Genes, Viral</term>
<term>Genome</term>
<term>Humans</term>
<term>Immunity, Innate</term>
<term>Models, Genetic</term>
<term>Models, Statistical</term>
<term>Oligonucleotide Array Sequence Analysis</term>
<term>Reverse Transcriptase Polymerase Chain Reaction</term>
<term>Up-Regulation</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Algorithmes</term>
<term>Analyse de regroupements</term>
<term>Biologie informatique</term>
<term>Expression des gènes</term>
<term>Gènes viraux</term>
<term>Génome</term>
<term>Humains</term>
<term>Immunité innée</term>
<term>Modèles génétiques</term>
<term>Modèles statistiques</term>
<term>RT-PCR</term>
<term>Régulation de l'expression des gènes viraux</term>
<term>Régulation positive</term>
<term>Séquençage par oligonucléotides en batterie</term>
<term>Test ELISA</term>
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<front><div type="abstract" xml:lang="en"><sec><title>Background</title>
<p>Severe acute respiratory syndrome (SARS), a recent epidemic human disease, is caused by a novel coronavirus (SARS-CoV). First reported in Asia, SARS quickly spread worldwide through international travelling. As of July 2003, the World Health Organization reported a total of 8,437 people afflicted with SARS with a 9.6% mortality rate. Although immunopathological damages may account for the severity of respiratory distress, little is known about how the genome-wide gene expression of the host changes under the attack of SARS-CoV.</p>
</sec>
<sec><title>Results</title>
<p>Based on changes in gene expression of peripheral blood, we identified 52 signature genes that accurately discriminated acute SARS patients from non-SARS controls. While a general suppression of gene expression predominated in SARS-infected blood, several genes including those involved in innate immunity, such as defensins and eosinophil-derived neurotoxin, were upregulated. Instead of employing clustering methods, we ranked the severity of recovering SARS patients by generalized associate plots (GAP) according to the expression profiles of 52 signature genes. Through this method, we discovered a smooth transition pattern of severity from normal controls to acute SARS patients. The rank of SARS severity was significantly correlated with the recovery period (in days) and with the clinical pulmonary infection score.</p>
</sec>
<sec><title>Conclusion</title>
<p>The use of the GAP approach has proved useful in analyzing the complexity and continuity of biological systems. The severity rank derived from the global expression profile of significantly regulated genes in patients may be useful for further elucidating the pathophysiology of their disease.</p>
</sec>
<sec><title>Electronic supplementary material</title>
<p>The online version of this article (doi:10.1186/1471-2164-6-132) contains supplementary material, which is available to authorized users.</p>
</sec>
</div>
</front>
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<institution>Department of Biotechnology,</institution>
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Tao-Yuan, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Tao-Yuan</wicri:regionArea>
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<author><name sortKey="Chen, Chun Houh" sort="Chen, Chun Houh" uniqKey="Chen C" first="Chun-Houh" last="Chen">Chun-Houh Chen</name>
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Taipei, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Taipei</wicri:regionArea>
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</author>
<author><name sortKey="Chao, Angel" sort="Chao, Angel" uniqKey="Chao A" first="Angel" last="Chao">Angel Chao</name>
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<institution-id institution-id-type="ISNI">000000041756999X</institution-id>
<institution>Department of Obstetrics and Gynecology,</institution>
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Tao-Yuan, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Tao-Yuan</wicri:regionArea>
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<institution>Graduate Institute of Clinical Medical Sciences, College of Medicine,</institution>
<institution>Chang Gung University,</institution>
</institution-wrap>
Tao-Yuan, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Tao-Yuan</wicri:regionArea>
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<author><name sortKey="Chen, En Shih" sort="Chen, En Shih" uniqKey="Chen E" first="En-Shih" last="Chen">En-Shih Chen</name>
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<country xml:lang="fr">Taïwan</country>
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</author>
<author><name sortKey="Wei, Min Li" sort="Wei, Min Li" uniqKey="Wei M" first="Min-Li" last="Wei">Min-Li Wei</name>
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<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital (CGMH), Tao-Yuan</wicri:regionArea>
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<author><name sortKey="Chen, Lung Kun" sort="Chen, Lung Kun" uniqKey="Chen L" first="Lung-Kun" last="Chen">Lung-Kun Chen</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1">Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital (CGMH), Tao-Yuan, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital (CGMH), Tao-Yuan</wicri:regionArea>
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<author><name sortKey="Yang, Kuender D" sort="Yang, Kuender D" uniqKey="Yang K" first="Kuender D" last="Yang">Kuender D. Yang</name>
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<institution-id institution-id-type="ISNI">0000000406209374</institution-id>
<institution>Department of Pediatrics,</institution>
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Kaohsiung, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Kaohsiung</wicri:regionArea>
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</author>
<author><name sortKey="Lin, Meng Chih" sort="Lin, Meng Chih" uniqKey="Lin M" first="Meng-Chih" last="Lin">Meng-Chih Lin</name>
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<institution-id institution-id-type="ISNI">0000000406209374</institution-id>
<institution>Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine,</institution>
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Kaohsiung, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Kaohsiung</wicri:regionArea>
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<author><name sortKey="Wang, Yi Hsi" sort="Wang, Yi Hsi" uniqKey="Wang Y" first="Yi-Hsi" last="Wang">Yi-Hsi Wang</name>
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<institution-id institution-id-type="ISNI">0000000406209374</institution-id>
<institution>Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine,</institution>
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Kaohsiung, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Kaohsiung</wicri:regionArea>
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<author><name sortKey="Liu, Jien Wei" sort="Liu, Jien Wei" uniqKey="Liu J" first="Jien-Wei" last="Liu">Jien-Wei Liu</name>
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<institution-id institution-id-type="ISNI">0000000406209374</institution-id>
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Kaohsiung, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Kaohsiung</wicri:regionArea>
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<author><name sortKey="Eng, Hock Liew" sort="Eng, Hock Liew" uniqKey="Eng H" first="Hock-Liew" last="Eng">Hock-Liew Eng</name>
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<institution-id institution-id-type="ISNI">0000000406209374</institution-id>
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Kaohsiung, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Kaohsiung</wicri:regionArea>
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<author><name sortKey="Chiang, Ping Cherng" sort="Chiang, Ping Cherng" uniqKey="Chiang P" first="Ping-Cherng" last="Chiang">Ping-Cherng Chiang</name>
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<institution-id institution-id-type="ISNI">000000041756999X</institution-id>
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Tao-Yuan, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Tao-Yuan</wicri:regionArea>
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</author>
<author><name sortKey="Wu, Ting Shu" sort="Wu, Ting Shu" uniqKey="Wu T" first="Ting-Shu" last="Wu">Ting-Shu Wu</name>
<affiliation wicri:level="1"><nlm:aff id="Aff10"><institution-wrap><institution-id institution-id-type="GRID">grid.454211.7</institution-id>
<institution-id institution-id-type="ISNI">000000041756999X</institution-id>
<institution>Department of Internal Medicine, Division of Infectious Diseases,</institution>
<institution>Lin-Kou Medical Center, CGMH,</institution>
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Tao-Yuan, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Tao-Yuan</wicri:regionArea>
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<author><name sortKey="Tsao, Kuo Chein" sort="Tsao, Kuo Chein" uniqKey="Tsao K" first="Kuo-Chein" last="Tsao">Kuo-Chein Tsao</name>
<affiliation wicri:level="1"><nlm:aff id="Aff11">Clinical Virology Laboratory, Department of Clinical Pathology, CGMH, Tao-Yuan, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Clinical Virology Laboratory, Department of Clinical Pathology, CGMH, Tao-Yuan</wicri:regionArea>
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<author><name sortKey="Huang, Chung Guei" sort="Huang, Chung Guei" uniqKey="Huang C" first="Chung-Guei" last="Huang">Chung-Guei Huang</name>
<affiliation wicri:level="1"><nlm:aff id="Aff11">Clinical Virology Laboratory, Department of Clinical Pathology, CGMH, Tao-Yuan, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Clinical Virology Laboratory, Department of Clinical Pathology, CGMH, Tao-Yuan</wicri:regionArea>
<wicri:noRegion>Tao-Yuan</wicri:noRegion>
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<author><name sortKey="Tien, Yin Jing" sort="Tien, Yin Jing" uniqKey="Tien Y" first="Yin-Jing" last="Tien">Yin-Jing Tien</name>
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<institution-id institution-id-type="ISNI">0000000405323167</institution-id>
<institution>Institute of Statistics,</institution>
<institution>National Central University,</institution>
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Tao-Yuan, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
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</affiliation>
</author>
<author><name sortKey="Wang, Tzu Hao" sort="Wang, Tzu Hao" uniqKey="Wang T" first="Tzu-Hao" last="Wang">Tzu-Hao Wang</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1">Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital (CGMH), Tao-Yuan, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital (CGMH), Tao-Yuan</wicri:regionArea>
<wicri:noRegion>Tao-Yuan</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.454211.7</institution-id>
<institution-id institution-id-type="ISNI">000000041756999X</institution-id>
<institution>Department of Obstetrics and Gynecology,</institution>
<institution>Lin-Kou Medical Center, CGMH,</institution>
</institution-wrap>
Tao-Yuan, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Tao-Yuan</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Wang, Hsing Shih" sort="Wang, Hsing Shih" uniqKey="Wang H" first="Hsing-Shih" last="Wang">Hsing-Shih Wang</name>
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<institution-id institution-id-type="ISNI">000000041756999X</institution-id>
<institution>Department of Obstetrics and Gynecology,</institution>
<institution>Lin-Kou Medical Center, CGMH,</institution>
</institution-wrap>
Tao-Yuan, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Tao-Yuan</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="GRID">grid.145695.a</institution-id>
<institution>Graduate Institute of Clinical Medical Sciences, College of Medicine,</institution>
<institution>Chang Gung University,</institution>
</institution-wrap>
Tao-Yuan, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Tao-Yuan</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Lee, Ying Shiung" sort="Lee, Ying Shiung" uniqKey="Lee Y" first="Ying-Shiung" last="Lee">Ying-Shiung Lee</name>
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<institution>Graduate Institute of Clinical Medical Sciences, College of Medicine,</institution>
<institution>Chang Gung University,</institution>
</institution-wrap>
Tao-Yuan, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Tao-Yuan</wicri:regionArea>
</affiliation>
</author>
</titleStmt>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Molecular signature of clinical severity in recovering patients with severe acute respiratory syndrome coronavirus (SARS-CoV)</title>
<author><name sortKey="Lee, Yun Shien" sort="Lee, Yun Shien" uniqKey="Lee Y" first="Yun-Shien" last="Lee">Yun-Shien Lee</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1">Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital (CGMH), Tao-Yuan, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital (CGMH), Tao-Yuan</wicri:regionArea>
<wicri:noRegion>Tao-Yuan</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.411804.8</institution-id>
<institution-id institution-id-type="ISNI">0000000405322834</institution-id>
<institution>Department of Biotechnology,</institution>
<institution>Ming Chuan University,</institution>
</institution-wrap>
Tao-Yuan, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Tao-Yuan</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Chen, Chun Houh" sort="Chen, Chun Houh" uniqKey="Chen C" first="Chun-Houh" last="Chen">Chun-Houh Chen</name>
<affiliation wicri:level="1"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.28665.3f</institution-id>
<institution-id institution-id-type="ISNI">0000000122871366</institution-id>
<institution>Institute of Statistical Science,</institution>
<institution>Academia Sinica,</institution>
</institution-wrap>
Taipei, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Taipei</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Chao, Angel" sort="Chao, Angel" uniqKey="Chao A" first="Angel" last="Chao">Angel Chao</name>
<affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.454211.7</institution-id>
<institution-id institution-id-type="ISNI">000000041756999X</institution-id>
<institution>Department of Obstetrics and Gynecology,</institution>
<institution>Lin-Kou Medical Center, CGMH,</institution>
</institution-wrap>
Tao-Yuan, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Tao-Yuan</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="GRID">grid.145695.a</institution-id>
<institution>Graduate Institute of Clinical Medical Sciences, College of Medicine,</institution>
<institution>Chang Gung University,</institution>
</institution-wrap>
Tao-Yuan, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Tao-Yuan</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Chen, En Shih" sort="Chen, En Shih" uniqKey="Chen E" first="En-Shih" last="Chen">En-Shih Chen</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1">Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital (CGMH), Tao-Yuan, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital (CGMH), Tao-Yuan</wicri:regionArea>
<wicri:noRegion>Tao-Yuan</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Wei, Min Li" sort="Wei, Min Li" uniqKey="Wei M" first="Min-Li" last="Wei">Min-Li Wei</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1">Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital (CGMH), Tao-Yuan, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital (CGMH), Tao-Yuan</wicri:regionArea>
<wicri:noRegion>Tao-Yuan</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Chen, Lung Kun" sort="Chen, Lung Kun" uniqKey="Chen L" first="Lung-Kun" last="Chen">Lung-Kun Chen</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1">Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital (CGMH), Tao-Yuan, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital (CGMH), Tao-Yuan</wicri:regionArea>
<wicri:noRegion>Tao-Yuan</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Yang, Kuender D" sort="Yang, Kuender D" uniqKey="Yang K" first="Kuender D" last="Yang">Kuender D. Yang</name>
<affiliation wicri:level="1"><nlm:aff id="Aff6"><institution-wrap><institution-id institution-id-type="GRID">grid.412027.2</institution-id>
<institution-id institution-id-type="ISNI">0000000406209374</institution-id>
<institution>Department of Pediatrics,</institution>
<institution>Kaohsiung Medical Center, CGMH,</institution>
</institution-wrap>
Kaohsiung, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Kaohsiung</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Lin, Meng Chih" sort="Lin, Meng Chih" uniqKey="Lin M" first="Meng-Chih" last="Lin">Meng-Chih Lin</name>
<affiliation wicri:level="1"><nlm:aff id="Aff7"><institution-wrap><institution-id institution-id-type="GRID">grid.412027.2</institution-id>
<institution-id institution-id-type="ISNI">0000000406209374</institution-id>
<institution>Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine,</institution>
<institution>Kaohsiung Medical Center, CGMH,</institution>
</institution-wrap>
Kaohsiung, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Kaohsiung</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Wang, Yi Hsi" sort="Wang, Yi Hsi" uniqKey="Wang Y" first="Yi-Hsi" last="Wang">Yi-Hsi Wang</name>
<affiliation wicri:level="1"><nlm:aff id="Aff7"><institution-wrap><institution-id institution-id-type="GRID">grid.412027.2</institution-id>
<institution-id institution-id-type="ISNI">0000000406209374</institution-id>
<institution>Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine,</institution>
<institution>Kaohsiung Medical Center, CGMH,</institution>
</institution-wrap>
Kaohsiung, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Kaohsiung</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Liu, Jien Wei" sort="Liu, Jien Wei" uniqKey="Liu J" first="Jien-Wei" last="Liu">Jien-Wei Liu</name>
<affiliation wicri:level="1"><nlm:aff id="Aff8"><institution-wrap><institution-id institution-id-type="GRID">grid.412027.2</institution-id>
<institution-id institution-id-type="ISNI">0000000406209374</institution-id>
<institution>Department of Internal Medicine, Division of Infectious Diseases,</institution>
<institution>Kaohsiung Medical Center, CGMH,</institution>
</institution-wrap>
Kaohsiung, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Kaohsiung</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Eng, Hock Liew" sort="Eng, Hock Liew" uniqKey="Eng H" first="Hock-Liew" last="Eng">Hock-Liew Eng</name>
<affiliation wicri:level="1"><nlm:aff id="Aff9"><institution-wrap><institution-id institution-id-type="GRID">grid.412027.2</institution-id>
<institution-id institution-id-type="ISNI">0000000406209374</institution-id>
<institution>Department of Pathology,</institution>
<institution>Kaohsiung Medical Center, CGMH,</institution>
</institution-wrap>
Kaohsiung, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Kaohsiung</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Chiang, Ping Cherng" sort="Chiang, Ping Cherng" uniqKey="Chiang P" first="Ping-Cherng" last="Chiang">Ping-Cherng Chiang</name>
<affiliation wicri:level="1"><nlm:aff id="Aff10"><institution-wrap><institution-id institution-id-type="GRID">grid.454211.7</institution-id>
<institution-id institution-id-type="ISNI">000000041756999X</institution-id>
<institution>Department of Internal Medicine, Division of Infectious Diseases,</institution>
<institution>Lin-Kou Medical Center, CGMH,</institution>
</institution-wrap>
Tao-Yuan, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Tao-Yuan</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Wu, Ting Shu" sort="Wu, Ting Shu" uniqKey="Wu T" first="Ting-Shu" last="Wu">Ting-Shu Wu</name>
<affiliation wicri:level="1"><nlm:aff id="Aff10"><institution-wrap><institution-id institution-id-type="GRID">grid.454211.7</institution-id>
<institution-id institution-id-type="ISNI">000000041756999X</institution-id>
<institution>Department of Internal Medicine, Division of Infectious Diseases,</institution>
<institution>Lin-Kou Medical Center, CGMH,</institution>
</institution-wrap>
Tao-Yuan, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Tao-Yuan</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Tsao, Kuo Chein" sort="Tsao, Kuo Chein" uniqKey="Tsao K" first="Kuo-Chein" last="Tsao">Kuo-Chein Tsao</name>
<affiliation wicri:level="1"><nlm:aff id="Aff11">Clinical Virology Laboratory, Department of Clinical Pathology, CGMH, Tao-Yuan, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Clinical Virology Laboratory, Department of Clinical Pathology, CGMH, Tao-Yuan</wicri:regionArea>
<wicri:noRegion>Tao-Yuan</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Huang, Chung Guei" sort="Huang, Chung Guei" uniqKey="Huang C" first="Chung-Guei" last="Huang">Chung-Guei Huang</name>
<affiliation wicri:level="1"><nlm:aff id="Aff11">Clinical Virology Laboratory, Department of Clinical Pathology, CGMH, Tao-Yuan, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Clinical Virology Laboratory, Department of Clinical Pathology, CGMH, Tao-Yuan</wicri:regionArea>
<wicri:noRegion>Tao-Yuan</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Tien, Yin Jing" sort="Tien, Yin Jing" uniqKey="Tien Y" first="Yin-Jing" last="Tien">Yin-Jing Tien</name>
<affiliation wicri:level="1"><nlm:aff id="Aff12"><institution-wrap><institution-id institution-id-type="GRID">grid.37589.30</institution-id>
<institution-id institution-id-type="ISNI">0000000405323167</institution-id>
<institution>Institute of Statistics,</institution>
<institution>National Central University,</institution>
</institution-wrap>
Tao-Yuan, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Tao-Yuan</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Wang, Tzu Hao" sort="Wang, Tzu Hao" uniqKey="Wang T" first="Tzu-Hao" last="Wang">Tzu-Hao Wang</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1">Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital (CGMH), Tao-Yuan, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital (CGMH), Tao-Yuan</wicri:regionArea>
<wicri:noRegion>Tao-Yuan</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.454211.7</institution-id>
<institution-id institution-id-type="ISNI">000000041756999X</institution-id>
<institution>Department of Obstetrics and Gynecology,</institution>
<institution>Lin-Kou Medical Center, CGMH,</institution>
</institution-wrap>
Tao-Yuan, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Tao-Yuan</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Wang, Hsing Shih" sort="Wang, Hsing Shih" uniqKey="Wang H" first="Hsing-Shih" last="Wang">Hsing-Shih Wang</name>
<affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.454211.7</institution-id>
<institution-id institution-id-type="ISNI">000000041756999X</institution-id>
<institution>Department of Obstetrics and Gynecology,</institution>
<institution>Lin-Kou Medical Center, CGMH,</institution>
</institution-wrap>
Tao-Yuan, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Tao-Yuan</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="GRID">grid.145695.a</institution-id>
<institution>Graduate Institute of Clinical Medical Sciences, College of Medicine,</institution>
<institution>Chang Gung University,</institution>
</institution-wrap>
Tao-Yuan, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Tao-Yuan</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Lee, Ying Shiung" sort="Lee, Ying Shiung" uniqKey="Lee Y" first="Ying-Shiung" last="Lee">Ying-Shiung Lee</name>
<affiliation wicri:level="1"><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="GRID">grid.145695.a</institution-id>
<institution>Graduate Institute of Clinical Medical Sciences, College of Medicine,</institution>
<institution>Chang Gung University,</institution>
</institution-wrap>
Tao-Yuan, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Tao-Yuan</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series><title level="j">BMC Genomics</title>
<idno type="eISSN">1471-2164</idno>
<imprint><date when="2005">2005</date>
</imprint>
</series>
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<front><div type="abstract" xml:lang="en"><sec><title>Background</title>
<p>Severe acute respiratory syndrome (SARS), a recent epidemic human disease, is caused by a novel coronavirus (SARS-CoV). First reported in Asia, SARS quickly spread worldwide through international travelling. As of July 2003, the World Health Organization reported a total of 8,437 people afflicted with SARS with a 9.6% mortality rate. Although immunopathological damages may account for the severity of respiratory distress, little is known about how the genome-wide gene expression of the host changes under the attack of SARS-CoV.</p>
</sec>
<sec><title>Results</title>
<p>Based on changes in gene expression of peripheral blood, we identified 52 signature genes that accurately discriminated acute SARS patients from non-SARS controls. While a general suppression of gene expression predominated in SARS-infected blood, several genes including those involved in innate immunity, such as defensins and eosinophil-derived neurotoxin, were upregulated. Instead of employing clustering methods, we ranked the severity of recovering SARS patients by generalized associate plots (GAP) according to the expression profiles of 52 signature genes. Through this method, we discovered a smooth transition pattern of severity from normal controls to acute SARS patients. The rank of SARS severity was significantly correlated with the recovery period (in days) and with the clinical pulmonary infection score.</p>
</sec>
<sec><title>Conclusion</title>
<p>The use of the GAP approach has proved useful in analyzing the complexity and continuity of biological systems. The severity rank derived from the global expression profile of significantly regulated genes in patients may be useful for further elucidating the pathophysiology of their disease.</p>
</sec>
<sec><title>Electronic supplementary material</title>
<p>The online version of this article (doi:10.1186/1471-2164-6-132) contains supplementary material, which is available to authorized users.</p>
</sec>
</div>
</front>
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<affiliation wicri:level="1"><nlm:affiliation>Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan. bojack@mcu.edu.tw</nlm:affiliation>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital, Tao-Yuan</wicri:regionArea>
<wicri:noRegion>Tao-Yuan</wicri:noRegion>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Molecular signature of clinical severity in recovering patients with severe acute respiratory syndrome coronavirus (SARS-CoV).</title>
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<country xml:lang="fr">Taïwan</country>
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<author><name sortKey="Wang, Tzu Hao" sort="Wang, Tzu Hao" uniqKey="Wang T" first="Tzu-Hao" last="Wang">Tzu-Hao Wang</name>
</author>
<author><name sortKey="Wang, Hsing Shih" sort="Wang, Hsing Shih" uniqKey="Wang H" first="Hsing-Shih" last="Wang">Hsing-Shih Wang</name>
</author>
<author><name sortKey="Lee, Ying Shiung" sort="Lee, Ying Shiung" uniqKey="Lee Y" first="Ying-Shiung" last="Lee">Ying-Shiung Lee</name>
</author>
</analytic>
<series><title level="j">BMC genomics</title>
<idno type="eISSN">1471-2164</idno>
<imprint><date when="2005" type="published">2005</date>
</imprint>
</series>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Algorithms</term>
<term>Cluster Analysis</term>
<term>Computational Biology</term>
<term>DNA, Complementary (metabolism)</term>
<term>Enzyme-Linked Immunosorbent Assay</term>
<term>Gene Expression</term>
<term>Gene Expression Regulation, Viral</term>
<term>Genes, Viral</term>
<term>Genome</term>
<term>Humans</term>
<term>Immunity, Innate</term>
<term>Lung Diseases (metabolism)</term>
<term>Lung Diseases (virology)</term>
<term>Models, Genetic</term>
<term>Models, Statistical</term>
<term>Oligonucleotide Array Sequence Analysis</term>
<term>Reverse Transcriptase Polymerase Chain Reaction</term>
<term>SARS Virus (genetics)</term>
<term>Severe Acute Respiratory Syndrome (blood)</term>
<term>Severe Acute Respiratory Syndrome (virology)</term>
<term>Up-Regulation</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>ADN complémentaire (métabolisme)</term>
<term>Algorithmes</term>
<term>Analyse de regroupements</term>
<term>Biologie informatique</term>
<term>Expression des gènes</term>
<term>Gènes viraux</term>
<term>Génome</term>
<term>Humains</term>
<term>Immunité innée</term>
<term>Maladies pulmonaires (métabolisme)</term>
<term>Maladies pulmonaires (virologie)</term>
<term>Modèles génétiques</term>
<term>Modèles statistiques</term>
<term>RT-PCR</term>
<term>Régulation de l'expression des gènes viraux</term>
<term>Régulation positive</term>
<term>Syndrome respiratoire aigu sévère (sang)</term>
<term>Syndrome respiratoire aigu sévère (virologie)</term>
<term>Séquençage par oligonucléotides en batterie</term>
<term>Test ELISA</term>
<term>Virus du SRAS (génétique)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>DNA, Complementary</term>
</keywords>
<keywords scheme="MESH" qualifier="blood" xml:lang="en"><term>Severe Acute Respiratory Syndrome</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>SARS Virus</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Virus du SRAS</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Lung Diseases</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>ADN complémentaire</term>
<term>Maladies pulmonaires</term>
</keywords>
<keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>Syndrome respiratoire aigu sévère</term>
</keywords>
<keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Maladies pulmonaires</term>
<term>Syndrome respiratoire aigu sévère</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Lung Diseases</term>
<term>Severe Acute Respiratory Syndrome</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Algorithms</term>
<term>Cluster Analysis</term>
<term>Computational Biology</term>
<term>Enzyme-Linked Immunosorbent Assay</term>
<term>Gene Expression</term>
<term>Gene Expression Regulation, Viral</term>
<term>Genes, Viral</term>
<term>Genome</term>
<term>Humans</term>
<term>Immunity, Innate</term>
<term>Models, Genetic</term>
<term>Models, Statistical</term>
<term>Oligonucleotide Array Sequence Analysis</term>
<term>Reverse Transcriptase Polymerase Chain Reaction</term>
<term>Up-Regulation</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Algorithmes</term>
<term>Analyse de regroupements</term>
<term>Biologie informatique</term>
<term>Expression des gènes</term>
<term>Gènes viraux</term>
<term>Génome</term>
<term>Humains</term>
<term>Immunité innée</term>
<term>Modèles génétiques</term>
<term>Modèles statistiques</term>
<term>RT-PCR</term>
<term>Régulation de l'expression des gènes viraux</term>
<term>Régulation positive</term>
<term>Séquençage par oligonucléotides en batterie</term>
<term>Test ELISA</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Severe acute respiratory syndrome (SARS), a recent epidemic human disease, is caused by a novel coronavirus (SARS-CoV). First reported in Asia, SARS quickly spread worldwide through international travelling. As of July 2003, the World Health Organization reported a total of 8,437 people afflicted with SARS with a 9.6% mortality rate. Although immunopathological damages may account for the severity of respiratory distress, little is known about how the genome-wide gene expression of the host changes under the attack of SARS-CoV.</div>
</front>
</TEI>
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