Background and 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. 
InterSIM: Simulation tool for multiple integrative ‘omic datasets’