A systems biological approach to identify key transcription and their genomic neighborhoods in human sarcomas

• Published in: Ai zheng Vol. 30; no. 1; pp. 27 - 40
• Main Author: Antti Ylipaa Olli Yli-Harja Wei Zhang Matti Nykter
• Format: Journal Article
• Language: Chinese
• Published: 2011
• Subjects: 人类; 基因组; 居民区; 生物方法; 系统生物学; 维生素D受体; 肉瘤; 转录因子
• ISSN: 1000-467X; 1944-446X

Identification of genetic signatures is the main objective for many computational oncology studies. The signature usually consists of numerous genes that are differentially expressed between two clinically distinct groups of samples, such as tumor subtypes. Prospectively, many signatures have been found to generalize poorly to other datasets and, thus, have rarely been accepted into clinical use. Recognizing the limited success of traditionally generated signatures, we developed a systems biology-based framework for robust identification of key transcription factors and their genomic regulatory neighborhoods. Application of the framework to study the differences between gastrointestinal stromal tumor （GIST） and leiomyosarcoma （LMS） resulted in the identification of nine transcription factors （SRF, NKX2-5, CCDC6, LEF1, VDR, ZNF250, TRIM63, MAF, and MYC）. Functional annotations of the obtained neighborhoods identified the biological processes which the key transcription factors regulate differently between the