title: A multi-layer inference approach to reconstruct condition-specific genes and their regulation.
abstract: An important topic in systems biology is the reverse engineering of regulatory mechanisms through reconstruction of context-dependent gene networks. A major challenge is to identify the genes and the regulations specific to a condition or phenotype, given that regulatory processes are highly connected such that a specific response is typically accompanied by numerous collateral effects. In this study, we design a multi-layer approach that is able to reconstruct condition-specific genes and their regulation through an integrative analysis of large-scale information of gene expression, protein interaction and transcriptional regulation (transcription factor-target gene relationships). We establish the accuracy of our methodology against synthetic datasets, as well as a yeast dataset. We then extend the framework to the application of higher eukaryotic systems, including human breast cancer and Arabidopsis thaliana cold acclimation. Our study identified TACSTD2 (TROP2) as a target gene for human breast cancer and discovered its regulation by transcription factors CREB, as well as NFkB. We also predict KIF2C is a target gene for ER-/HER2- breast cancer and is positively regulated by E2F1. The predictions were further confirmed through experimental studies.
  
  
  BACKGROUND
  The implementation and detailed protocol of the layer approach is available at http://www.egr.msu.edu/changroup/Protocols/Three-layer%20approach%20 to % 20reconstruct%20condition.html.
authors.affiliation: Department of Computer Science and Engineering, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Wu
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Hussein
authors.initials: H
authors.lastname: Hijazi
authors.forename: Christina
authors.initials: C
authors.lastname: Chan
mesh_terms: D000064:Acclimatization; D000951:Antigens, Neoplasm / Q000235:genetics; D017360:Arabidopsis / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics; D003080:Cold Temperature; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015966:Gene Expression Regulation, Fungal; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D049490:Systems Biology / Q000379:methods; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; C499380:TACSTD2 protein, human; D014157:Transcription Factors