title: Tissue-specific gene expression templates for accurate molecular characterization of the normal physiological states of multiple human tissues with implication in development and cancer studies.
abstract: BACKGROUND
  To elucidate the molecular complications in many complex diseases, we argue for the priority to construct a model representing the normal physiological state of a cell/tissue.
  
  
  RESULTS
  By analyzing three independent microarray datasets on normal human tissues, we established a quantitative molecular model GET, which consists of 24 tissue-specific Gene Expression Templates constructed from a set of 56 genes, for predicting 24 distinct tissue types under disease-free condition. 99.2% correctness was reached when a large-scale validation was performed on 61 new datasets to test the tissue-prediction power of GET. Network analysis based on molecular interactions suggests a potential role of these 56 genes in tissue differentiation and carcinogenesis.Applying GET to transcriptomic datasets produced from tissue development studies the results correlated well with developmental stages. Cancerous tissues and cell lines yielded significantly lower correlation with GET than the normal tissues. GET distinguished melanoma from normal skin tissue or benign skin tumor with 96% sensitivity and 89% specificity.
  
  
  CONCLUSIONS
  These results strongly suggest that a normal tissue or cell may uphold its normal functioning and morphology by maintaining specific chemical stoichiometry among genes. The state of stoichiometry can be depicted by a compact set of representative genes such as the 56 genes obtained here. A significant deviation from normal stoichiometry may result in malfunction or abnormal growth of the cells.
authors: Institute of Statistical Science, Academia Sinica, Taipei, Taiwan 115, Republic of China.
authors: Pei-Ing
authors: PI
authors: Hwang
authors: Huan-Bin
authors: HB
authors: Wu
authors: Chin-Di
authors: CD
authors: Wang
authors: Bai-Ling
authors: BL
authors: Lin
authors: Cheng-Tao
authors: CT
authors: Chen
authors: Shinsheng
authors: S
authors: Yuan
authors: Guani
authors: G
authors: Wu
authors: Ker-Chau
authors: KC
authors: Li
mesh_terms: D002460:Cell Line; D016000:Cluster Analysis; D030541:Databases, Genetic; D020869:Gene Expression Profiling / Q000379:methods*; D053263:Gene Regulatory Networks; D015894:Genome, Human; D006801:Humans; D058977:Molecular Sequence Annotation; D009369:Neoplasms / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity; D012680:Sensitivity and Specificity; D012867:Skin / Q000378:metabolism