title: Identification of phenotype deterministic genes using systemic analysis of transcriptional response.
abstract: Systemic identification of deterministic genes for different phenotypes is a primary application of high-throughput expression profiles. However, gene expression differences cannot be used when the differences between groups are not significant. Therefore, novel methods incorporating features other than expression differences are required. We developed a promising method using transcriptional response as an operational feature, which is quantified as the correlation between expression levels of pathway genes and target genes of the pathway. We applied this method to identify causative genes associated with chemo-sensitivity to tamoxifen and epirubicin. Genes whose transcriptional response was dysregulated only in the drug-resistant patient group were chosen for in vitro validation in human breast cancer cells. Finally, we discovered two genes responsible for tamoxifen sensitivity and three genes associated with epirubicin sensitivity. The method we propose here can be widely applied to identify deterministic genes for different phenotypes with only minor differences in gene expression levels.
authors.affiliation: Department of Bio and Brain Engineering, KAIST, Daejeon, 305-701, Republic of Korea.
authors.forename: Jungsul
authors.initials: J
authors.lastname: Lee
authors.affiliation: 1] Department of Bio and Brain Engineering, KAIST, Daejeon, 305-701, Republic of Korea [2] KAIST Institute for the BioCentury, Daejeon, 305-701, Republic of Korea.
authors.forename: Junseong
authors.initials: J
authors.lastname: Park
authors.affiliation: 1] Department of Bio and Brain Engineering, KAIST, Daejeon, 305-701, Republic of Korea [2] KAIST Institute for the BioCentury, Daejeon, 305-701, Republic of Korea [3] Graduate School of Medical Science and Engineering, KAIST, Daejeon, 305-701, Republic of Korea.
authors.forename: Chulhee
authors.initials: C
authors.lastname: Choi
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D030541:Databases, Genetic; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015251:Epirubicin / Q000627:therapeutic use; D005260:Female; D005838:Genotype; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D013629:Tamoxifen / Q000627:therapeutic use; D014158:Transcription, Genetic
chemical_list: D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D013629:Tamoxifen; D015251:Epirubicin