Top-down Proteomics: The Large-scale Proteoform Identification

With the rapid advancement of the high resolution mass spectrometry, top-down proteomics becomes the reality. Proteome research on the intact protein level will provide more precise and more abundant biological information. For example, it can detect the relationship between the multiple post-translational modifications. Due to the genetic mutation, alternative splicing of RNA and various post-translational modifications, one gene may produce multiple protein forms, now called 'proteoforms'. Top-down proteomics will help identify the proteoforms. The three pillar technologies in top-down proteomics are separation, mass spectrometry and bioinformatics from the point of view on the entire proteins. This paper reviews these technologies and puts more emphases on the bioinformatics related topics, including the mass spectral preprocessing, the database searching algorithms and the localization of post-translational modifications.