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Application of Proteomics 2018

The document discusses several applications of proteomics, including linking genes and diseases, understanding protein structure and interactions, and identifying biomarkers for various diseases like cancer. Specifically, it outlines how proteomics can be used to study protein expression differences between normal and diseased cells, understand three dimensional protein structures, and reveal protein functions and interactions. It also describes concepts like the diseasome, disease gene networks, and using body fluids like blood, urine and cerebrospinal fluid to identify biomarkers for diseases.

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Dr. Lehrasip Ali
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42 views19 pages

Application of Proteomics 2018

The document discusses several applications of proteomics, including linking genes and diseases, understanding protein structure and interactions, and identifying biomarkers for various diseases like cancer. Specifically, it outlines how proteomics can be used to study protein expression differences between normal and diseased cells, understand three dimensional protein structures, and reveal protein functions and interactions. It also describes concepts like the diseasome, disease gene networks, and using body fluids like blood, urine and cerebrospinal fluid to identify biomarkers for diseases.

Uploaded by

Dr. Lehrasip Ali
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PPTX, PDF, TXT or read online on Scribd
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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

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