A targeted re-sequencing simulator that generates synthetic exome sequencing reads from a given sample genome. Wessim emulates conventional exome capture technologies, including Agilent’s SureSelect and NimbleGen’s SeqCap, to generate DNA fragments from genomic target regions. The target regions can be either specified by genomic coordinates or inferred from in silico probe hybridization. Coupled with existing next-generation sequencing simulators, Wessim generates a realistic artificial exome sequencing data, which is essential for developing and evaluating exome-targeted variant callers.