A computational framework with simulation-based error models for inferring genomic structural variants from massive paired-end sequencing data. The package is composed of three modules, PEMer workflow, SV-Simulation and BreakDB. PEMer workflow is a sensitive software for detecting SVs from paired-end sequence reads. SV-Simulation randomly introduces SVs into a given genome and generates simulated paired-end reads from the ‘novel’ genome. Subsequent analysis with PEMer workflow on the simulated reads can facilitate parameterize PEMer workflow. BreakDB is a web accessible database developed to store, annotate and dsplay SV breakpoint events identified by PEMer and from other sources.