In general, Shotgun Proteomics, or LC-MS/MS, provides information across an entire range of proteins within a sample by measuring for the most prevalent peptides as observed during the experiment. 

Such survey proteomics does not consider already available information about the proteins related to your interest.  Instead, shotgun proteomics tries to identify in a random way as many proteins in a sample as possible. While this approach provides a snapshot of proteins present in a sample, there are limitations to the number of samples to be analyzed, the reproducibility across samples, and the ability to quantify proteins.

Both survey (shotgun) and targeted (MRM) mass spectrometry proteomics rely on the separation of peptide mixtures by liquid-chromatography. Peptides are separated on a column packed with a sorbent based on a chemical property (e.g. hydrophobicity) and are directly analyzed by a mass spectrometer. The difference between survey and targeted proteomics relies in the type of mass spectrometer, it’s operation, and therefore the range and quality of the data generated.

In a Shotgun proteomics experiment, the mass spectrometer selects peptides eluting from the liquid-chromatography column and fragments them. A fragment spectrum of a peptide is specific to its nature, and thus can be used to accurately identify the peptide and its original protein, like a fingerprint is used to identify a person. The amount of the peptide can be determined by its signal intensity in the mass spectrometer, offering quantitative measurements. The mass spectrometer selects peptides for fragmentation based on its abundance, starting from the most abundant peptides. However, this data dependent approach way limits the practial sensitivity and sample throughput.