Question

• What is the utility of proteomic analysis in understanding and treating human disease?
• How does proteomics help us connect genotype to phenotype?
• In comparing the protein content of a healthy cell to that of a diseased cell, are you able to definitively describe phenotype?
• Speculate on additional protein information you might need to better understand human disease.

Answer 1

Utility of proteomics analysis and human diseases

Proteomics is a large scale study of proteins and protein variations,that contributes to a better understanding of the molecular basis of variability in susceptibility to diseases that are associated with genetic diversity and environmental factors. Information obtained from proteomics will allow  :

- decode the pathogenic mechanisms underlying diseases

-elucidate potential risk factors and molecular targets for drug development and therapeutic interventions

-identify promising biomolecules that could be developed for diagnostic and prognostic purposes and for improved disease management strategies.

Correlation genotype - phenotype through proteomics analysis

It is known that understanding of the genome alone, that means , without the necessary knowledge of the encoded gene products, does not permit clear extrapolations regarding the complex biological processes that occur in the cells.

There is a large gap in predicting phenotype from genotype. Proteins functionally govern cellular processes and execute activities dictated by genes to determine the cellular phenotype and the targets of natural selection. They are involved in virtually every cellular function and processes and perform all the work of biological systems.

So genomics alone cannot provide information regarding the dynamics of protein- protein interactions, which are the key to determine the biological mechanisms and functional consequences of the expression of the diverse proteins associated with disease.

The development of proteomics, aimed at decoding the information contained in the genomic sequences in terms of protein structures and functions,  to fill the gap between genomic information and functional proteins improving the knowledge that allows the  understanding of the biology system dynamics.

Proteomic analysis enables the molecular characterization of various human diseases and the ability to depicted the molecular mechanisms that triggers the initiation and progression of the disease.

Protein content vs. phenotype

Disease involves alterations in protein expression levels. Hence, by studying the change in the abundance of proteins between different cellular states (normal vs. diseased states), proteomics provide insights into the pathophysiological basis of protein target identification and validation for intervention and treatment of disease.

Specific biomarkers identified from proteomics may be used in the diagnosis and prognosis of diseases.

But there are exceptions, in which environmental factors or multigenic processes can also be determinants in the expression of a particular phenotype

For example, there are proteins that have various isoforms and variants. On average, a single gene can produce up to three proteins. These proteins can then undergo post-translational modifications which can further increase their functional diversity.

Also, various gene products and their modifications have differential tissue expression and function.

So, comparison of protein levels between healthy cells and diseased cell is not enough information to elucidate the phenotype. More informations have to be considered.