APPLICATIONS OF PROTEOMICS

Sanaullah Iqbal
APPLICATIONS OF PROTEOMICS

 link among genes, proteins, and diseases, as well as the possible

intervention of a disease by medicine, was suggested by the one-
gene-one-enzyme theory of Beadle and Tatum in 1941
 particular protein controlling the cellular structure or a metabolic
reaction is either missing or defective in a person who has a
heritable disease
 the one-gene-one-enzyme concept became the basis of medical
treatment by providing insulin
 Monogenic and Polygenic Concepts
APPLICATIONS OF PROTEOMICS

list of all known genes controlling human diseases

with their biochemical defects are complied by
Victor McKusick (1966, 1998) of Johns Hopkins
University
Online Mendelian Inheritance of Man (OMIM) -- 1777
genes and 1284 human disorders
HUPO and HUGO
 TYPES OF PROTEOMICS
Expression proteomics
 Expression proteomics is used to study the qualitative and quantitative
expression of total proteins under two different conditions.
 Comparison of responsible protein in normal and treated or diseased cell
 Typically, expression proteomics studies are addressed to the
investigation of the expression protein patterns in abnormal cells
 Compare tumor tissue sample and the normal tissue can be analyzed for
differential protein expression
TYPES OF PROTEOMICS

Structural proteomics
 Structural proteomics helps to understand three dimensional shape and
structural complexities of functional proteins.
 It is possible to identify all the proteins present in a complex system
such as membranes, ribosomes, and cell organelles and to characterize
all the protein interactions that can be possible between these proteins
and protein complexes.
 Different technologies such as X-ray crystallography and
NMR spectroscopy were mainly used for structure determination
TYPES OF PROTEOMICS

 Functional proteomics
 Functional proteomics explains understanding the protein
functions as well as unrevealing molecular mechanisms within
the cell then depend on the identification of the interacting
protein partners.
 The association of an unknown protein with partners belonging
to a specific protein complex involved in a particular mechanism
would in fact, be strongly suggestive of its biological function
DISEASOME

 Conceptualized first by Marc Vidal and his group at Harvard

University in 2007
 It attempts to establish a link between the gene (disease genome)
and the disorder (disease phenome) in humans.
 Many human diseases are monogenic
 Mutations in TP53 have been known to produce cancer with 11
different phenotypes
 Zellweger syndrome can result from a mutation in any of 11
different genes
DISEASE GENE NETWORK
(DGN)
HUMAN DISEASE
NETWORK
(HDN)
BODY FLUID PROTEOME

 Flows through the body and comes in contact with several

tissues of different organs in the body -------- ideal biomarker
 major technical challenge --------- large variation in the
amount of a particular protein in different individuals and
among the different samples taken at different times from
the same individual.
 Many individuals must be investigated under different times
or conditions to establish a baseline amount for a particular
protein
 BODY FLUID PROTEOME
BLOOD/ PLASMA/SERUM PROTEOME
 Serum: More than 4000 proteins have been identified from
human plasma
 2 limitations
 plasma contains a large number of proteins, in which it is difficult to
access the relative abundance of a particular protein
 difficult to identify a biomarker in proteins of low abundance
 Saliva: 1950s, saliva was considered to contain only two proteins
amylase and mucin ---- mixture of proteins, carbohydrates, & lipids
 Proximal fluid
BODY FLUID PROTEOME
 Human urine contained 946 unique proteins not found in any
other of these proximal fluids
 178 proteins specific to tears were found. Many biomarkers were
found exclusively in urine; include
 Corticotropin-lipotropin ------ marker for pituitary tumors
 Kallikarin II ------ marker for ovarian cancer
 Prostate secretory protein (PSP94), prostate acid phosphatase -
--- prostate disease
 Pancreatic secretory trypsin inhibitor ------- pancreatic diseases
BODY FLUID PROTEOME

 Cerebrospinal Fluid
 Biomarkers for Alzheimer disease, Parkinson disease, and
multiple sclerosis
 apolipoprotein Al, cathepsin D, and hemopexin ------
downregulated in Alzheimer patients
BODY FLUID PROTEOME

 Liver proteome
 liver is an important organ from biological, physiological,
pathological, and pharmacological points of view
 It is second only to the brain in terms of size and complexity.
 Controls digestive function, formation of embryonic red blood
cells, immune function, and detoxification of xenobiotics in body
 liver is subject to liver cancer, liver cirrhosis, caused by alcohol
intake, and viral hepatitis
 HUPO liver proteome project has identified > 5000 unique proteins
BODY FLUID PROTEOME

 Brain proteome
 Heart/cardiovascular proteome
 Cancer proteome
 CANCER PROTEOME
 Cancer is a devastating disease that claimed more than 7 million lives world wide in 2005

 biology of cancer is complex

 many genes and several environmental factors are involved in cancer tissues and disease, organs
differ in their mechanism of the development of several types of cancers
 major aim of proteomics has been to identify a protein or a group of proteins that can serve as a
biomarker for an early detection of a specific cancer before its clinical manifestation, as
evidenced by biopsy and/or histological analysis of the tissue involved in a particular kind of
cancer.
 Many biomarkers specific for a particular cancer have been reported. However, most of these are
not yet applicable in clinical diagnosis or treatment of any cancer except for PSA
 CANCER PROTEOME
 the level of PSA is not 100% reliable because other factors may cause changes in its level,
but an increase in its level certainly makes the attending physician cautious about the
possible onset of prostate cancer.
 Another antigen that promises to be of use in the primary care of ovarian cancer patients
is cancer antigen-125 (CA-125)
 The level of CEA is found to increase in individuals with colorectal cancer as well as in
patients with breast, lung, and pancreatic cancers

 A concept regarding the use of several markers has been developed