High Abundance Proteins: Proteomer’s Thorns in the Flesh?

Identification of low-abundance proteins is one of the major challenges in Proteomics because of the high dynamic range of the protein concentration in the biological samples [1]. Therefore, one of the prime objectives of the proteomers is to reduce the dynamic protein concentration range to shed a light on the “low-abundance proteome” or sometimes referred as “Hidden Proteome” [2]. The development and utilization of latest mass spectrometers have increased the sensitivity of the protein identification, fostering the identification of proteins present in extremely small amounts (up to attomoles, in isolation) [3]. However, the identification of low-abundance proteins during the analysis of whole cell/tissue proteome is still not achievable without any prefractionation of the samples [4]. One of the major reasons of this limited resolution, during total proteome analysis, is the presence of high-abundance proteins which occupies a major portion of the cell/ tissue proteome. Albumin in blood [1], RuBisCO in green leaves [5], and storage proteins in seeds, tubers, and roots [6] are some of the common examples of the high-abundance proteins in the biological samples. These high abundance proteins are products of the genes which are present in large copy numbers and inevitably impede the identification and characterization of low abundance proteins. Biomarkers or signaling/regulatory proteins are generally lowabundance in nature and are masked by the presence of these abundant proteins which are present in numbers 105-106 copies per cell [2,7,8]. As an example, 22 most abundant proteins, in the human blood plasma, constitute approximately 99% of the total plasma proteome with lowabundance proteins present as only 1% of the total plasma proteome [9]. Because of the presence of these high-abundance proteins, proteomics studies majorly ends up with the repeated identification of different components of these abundant or house-keeping proteins and thus actual information of the biological phenomenon remains concealed. The possibility to look beyond these abundant proteins or go further lies on the successful enrichment and identification of the lowabundance proteins which are present less than 100 copies per cell [7].