Textbook of Personalized Medicine - Second Edition [2015]

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The industrial sector is taking a lead in developing this area. Individualized
therapy may be based on differential protein expression rather than a genetic
polymorphism.
Proteomics had a great impact on diagnosis during the fi rst decade of the twenty-
fi rst century. By the end of the second decade protein chip-based tests will be avail-
able for several diseases. Knowledge gained from genomics and proteomics will be
combined to provide optimal detection of disease at an early stage for prevention or
early intervention. Proteomics-based molecular diagnostics will have an important
role in the diagnosis of certain conditions and proteomics-based medicines would
be integrated in the total healthcare of a patient.
Proteomics plays an important role in systems biology because most biological
systems involve proteins. Proteins that are disturbed by disease and gene regulatory
networks differ from their normal counterparts and these differences may be
detected by multiparameter measurements of the blood. This will have a major role
in creating a predictive, personalized, preventive, and participatory approach to
medicine.


Proteomic Approaches to the Study of Pathophysiology


of Diseases


Most of the human diseases are multifactorial and their complexity needs to be
understood at the molecular level. Genomic sequencing and mRNA-based analysis
of gene expression has provided important information but purely gene-based
expression data is not adequate for dissection of the disease phenotype at the molec-
ular level. There is no strict correlation between the gene and the actual protein
expression. Therefore, the cell’s full proteome cannot be deciphered by analysis at
the genetic level alone. It is necessary to look at the proteins directly to understand
the disease at a molecular level. Aberrations in the interaction of proteins with one
another are at the heart of the molecular basis of many diseases. For example,
genomic analysis alone may not suffi ce in type 2 diabetes mellitus as the insulin
gene may be normal and the disease may arise from an abnormality at any point in
the complicated pathway that involves insulin and the complex proteins with which
it interacts. Discovery of the mutations in BRCA1 and BRCA2 genes in familial
breast cancer has not led to design of a curative therapy because function of the
proteins coded by the genes is unknown. Analysis of different levels of gene expres-
sion in healthy and diseased tissues by proteomic approaches is as important as the
detection of mutations and polymorphisms at the genomic level and may be of more
value in designing a rational therapy.
The proteome is dynamic and refl ects the conditions, such as a disease, to which
a cell is exposed. Combining the genomic with the proteomics information would,
therefore, reveal a more dynamic picture of the disease process. An example of the
use of proteomics in understanding pathophysiology of disease is the study of


6 Pharmacoproteomics
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