Discovering human protein diversity

Dobrin Nedelkov

Abstract


Current emphasis on discovering and correlating human genetic variations lays the foundation for future studies of human protein diversity. Protein posttranslational processing, along with the translation of genetic variations, results in a complex, variable human proteome. Analyzing these protein variations on a grandeur scale has become feasible with the advent of mass spectrometry. Mass spectrometry is the only detection method today that can universally provide information about specific protein structural modifications, without a priori knowledge of the modification. However, high-throughput separation approaches are needed to effectively prepare the proteins for mass spectrometric interrogation. Such are the immunoaffinity separations that target single proteins by using highly specific antibodies for their affinity retrieval from the biological fluids. The resulting combination of immunoaffinity separation with MALDI-TOF mass spectrometry, termed Mass Spectrometric Immunoassay (MSIA), has been recently applied in two large studies of protein diversity. The results of these studies reveal a human protein diversity that is far more complex than the variations observed at the genetic level. Assessing the human proteome variations among and within populations will be an important future undertaking with significant clinical and diagnostic implications.


Keywords


protein diversity; population proteomics; protein isoforms; plasma; serum; mass spectrometry; immunoassay

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References


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DOI: http://dx.doi.org/10.20450/mjcce.2008.229

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