A system and method are providing for analyzing radiation signature data (i.e., spectral data) produced by a detector device against stored data representing the computed interaction of known radioisotopic spectra with a representative cross section for each of a small number of material groups. Each material group comprises materials expected to be in a detection path of the detector and which exhibit similar cross sections. Comparative analysis is made of the spectral data received from the detector for threat materials to determine whether the spectral data indicates presence of a threat material in the interrogated space. The system and method is not limited to any particular detector type, and may be used with any detector that produces spectral data.