title: A dynamic time order network for time-series gene expression data analysis.
abstract: BACKGROUND
  Typical analysis of time-series gene expression data such as clustering or graphical models cannot distinguish between early and later drug responsive gene targets in cancer cells. However, these genes would represent good candidate biomarkers.
  
  
  RESULTS
  We propose a new model - the dynamic time order network - to distinguish and connect early and later drug responsive gene targets. This network is constructed based on an integrated differential equation. Spline regression is applied for an accurate modeling of the time variation of gene expressions. Then a likelihood ratio test is implemented to infer the time order of any gene expression pair. One application of the model is the discovery of estrogen response biomarkers. For this purpose, we focused on genes whose responses are late when the breast cancer cells are treated with estradiol (E2).
  
  
  CONCLUSIONS
  Our approach has been validated by successfully finding time order relations between genes of the cell cycle system. More notably, we found late response genes potentially interesting as biomarkers of E2 treatment.
authors.affiliation: Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Pengyue
authors.initials: P
authors.lastname: Zhang
authors.forename: Raphaël
authors.initials: R
authors.lastname: Mourad
authors.forename: Yang
authors.initials: Y
authors.lastname: Xiang
authors.forename: Kun
authors.initials: K
authors.lastname: Huang
authors.forename: Tim
authors.initials: T
authors.lastname: Huang
authors.forename: Kenneth
authors.initials: K
authors.lastname: Nephew
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Liu
authors.forename: Lang
authors.initials: L
authors.lastname: Li
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods*; D030541:Databases, Genetic; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005819:Genetic Markers; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D046228:Microarray Analysis; D008957:Models, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results
chemical_list: D005819:Genetic Markers; D012333:RNA, Messenger; D004958:Estradiol