The untiring search for the most complete proteome representation: reviewing the methods.

Proteomic research has proved valuable for understanding the molecular mechanisms of biological processes, as well as in the search for biomarkers for a variety of diseases which lack a molecular diagnostic. While several new approaches are being developed, two-dimensional (2-DE) gel electrophoresis is still one of the most commonly used techniques, despite its many limitations. However, for biomarker research, 2-DE gel electrophoresis alone does not fulfill the necessary pre-requisites. If such a technique is utilized exclusively, a great part of a given proteome remains unseen. Therefore, very precise and sensitive techniques are needed. Here, we present a brief review of known methodologies that try to overcome the limitations of conventional proteome analysis as well as their respective advantages and limitations.