title: InterSIM: Simulation tool for multiple integrative 'omic datasets'.
abstract: OBJECTIVE
  Integrative approaches for the study of biological systems have gained popularity in the realm of statistical genomics. For example, The Cancer Genome Atlas (TCGA) has applied integrative clustering methodologies to various cancer types to determine molecular subtypes within a given cancer histology. In order to adequately compare integrative or "systems-biology"-type methods, realistic and related datasets are needed to assess the methods. This involves simulating multiple types of 'omic data with realistic correlation between features of the same type (e.g., gene expression for genes in a pathway) and across data types (e.g., "gene silencing" involving DNA methylation and gene expression).
  
  
  METHODS
  We present the software application tool InterSIM for simulating multiple interrelated data types with realistic intra- and inter-relationships based on the DNA methylation, mRNA gene expression, and protein expression from the TCGA ovarian cancer study.
  
  
  RESULTS
  The resulting simulated datasets can be used to assess and compare the operating characteristics of newly developed integrative bioinformatics methods to existing methods. Application of InterSIM is presented with an example of heatmaps of the simulated datasets.
  
  
  CONCLUSIONS
  InterSIM allows researchers to evaluate and test new integrative methods with realistically simulated interrelated genomic datasets. The software tool InterSIM is implemented in R and is freely available from CRAN.
authors.affiliation: Department of Biostatistics, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS 66160, United States. Electronic address: pchalise@kumc.edu.
authors.forename: Prabhakar
authors.initials: P
authors.lastname: Chalise
authors.affiliation: Department of Biostatistics, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS 66160, United States. Electronic address: rraghavan@kumc.edu.
authors.forename: Rama
authors.initials: R
authors.lastname: Raghavan
authors.affiliation: Department of Biostatistics, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS 66160, United States. Electronic address: bfridley@kumc.edu.
authors.forename: Brooke L
authors.initials: BL
authors.lastname: Fridley
mesh_terms: D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D018899:CpG Islands; D019175:DNA Methylation; D030541:Databases, Genetic; D005260:Female; D020869:Gene Expression Profiling; D020868:Gene Silencing; D015894:Genome, Human; D023281:Genomics / Q000379:methods*; D006801:Humans; D010051:Ovarian Neoplasms / Q000235:genetics; D040901:Proteomics / Q000379:methods*; D012333:RNA, Messenger / Q000378:metabolism; D015203:Reproducibility of Results; D012984:Software; D049490:Systems Biology
chemical_list: D012333:RNA, Messenger
keywords: Clustering; Integrative; NMF; Simulation