title: A systems biological approach to identify key transcription factors and their genomic neighborhoods in human sarcomas.
abstract: 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 tumor types. Analyzing the differences in the expression patterns using our approach resulted in a more robust genetic signature and more biological insight into the diseases compared to a traditional genetic signature.
authors.affiliation: Department of Signal Processing, Tampere University of Technology, Tampere 33101, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Ylipää
authors.forename: Olli
authors.initials: O
authors.lastname: Yli-Harja
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Matti
authors.initials: M
authors.lastname: Nykter
mesh_terms: D005770:Gastrointestinal Neoplasms / Q000235:genetics / Q000378:metabolism; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007890:Leiomyosarcoma / Q000235:genetics / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D049490:Systems Biology / Q000379:methods; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D014157:Transcription Factors