Despite these concerns regarding the perils of fractionation, there is one overriding advantage to fractionating proteomes for analysis: it simplifies them. Remember that our ability to detect multiple protein species in a sample depends on our ability to resolve many peptides from the sample and obtain MS data on as many of them as possible. Selection of a subcellular fraction (e.g., the mitochondria) for analysis reduces the task from analysis of perhaps 25,000 proteins in a human cell sample to analysis of about 1000–2000. With current technology, we have a better chance of identifying less abundant proteins when they are present in a mixture of 1000 proteins than when they are in a mixture of 15,000 proteins. Consequently, the best current approach to proteome analysis in a cell or tissue sample may be to fractionate the sample first either on the basis of subcellular fractions. For simpler proteomes (e.g., CSF) such a prefractionation may be unnecessary.