title: Molecular signature of clinical severity in recovering patients with severe acute respiratory syndrome coronavirus (SARS-CoV).
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan. bojack@mcu.edu.tw
authors.forename: Yun-Shien
authors.initials: YS
authors.lastname: Lee
authors.forename: Chun-Houh
authors.initials: CH
authors.lastname: Chen
authors.forename: Angel
authors.initials: A
authors.lastname: Chao
authors.forename: En-Shih
authors.initials: ES
authors.lastname: Chen
authors.forename: Min-Li
authors.initials: ML
authors.lastname: Wei
authors.forename: Lung-Kun
authors.initials: LK
authors.lastname: Chen
authors.forename: Kuender D
authors.initials: KD
authors.lastname: Yang
authors.forename: Meng-Chih
authors.initials: MC
authors.lastname: Lin
authors.forename: Yi-Hsi
authors.initials: YH
authors.lastname: Wang
authors.forename: Jien-Wei
authors.initials: JW
authors.lastname: Liu
authors.forename: Hock-Liew
authors.initials: HL
authors.lastname: Eng
authors.forename: Ping-Cherng
authors.initials: PC
authors.lastname: Chiang
authors.forename: Ting-Shu
authors.initials: TS
authors.lastname: Wu
authors.forename: Kuo-Chein
authors.initials: KC
authors.lastname: Tsao
authors.forename: Chung-Guei
authors.initials: CG
authors.lastname: Huang
authors.forename: Yin-Jing
authors.initials: YJ
authors.lastname: Tien
authors.forename: Tzu-Hao
authors.initials: TH
authors.lastname: Wang
authors.forename: Hsing-Shih
authors.initials: HS
authors.lastname: Wang
authors.forename: Ying-Shiung
authors.initials: YS
authors.lastname: Lee
mesh_terms: D000465:Algorithms; D016000:Cluster Analysis; D019295:Computational Biology; D018076:DNA, Complementary / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral; D016678:Genome; D006801:Humans; D007113:Immunity, Innate; D008171:Lung Diseases / Q000378:metabolism / Q000821:virology; D008957:Models, Genetic; D015233:Models, Statistical; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D045473:Severe acute respiratory syndrome-related coronavirus / Q000235:genetics*; D045169:Severe Acute Respiratory Syndrome / Q000097:blood / Q000821:virology*; D015854:Up-Regulation
chemical_list: D018076:DNA, Complementary