application_of_bioinformatics_in_various_fields.ppt

Bioinformatics: A New Discipline
or
A Jewel in the Crown of CS
Prof Allam Appa Rao
Andhra University
www.allamapparao.net

A recent google search
for "definition of
bioinformatics" returned
over 43,000 results!
Bioinformatics - What it is ?

Bioinformatics:
A subject that teaches
application of computational tools
and approaches for expanding the
use of biological, medical,
behavioral, health and other data,
including those to acquire, store,
organize, archive, analyze and
visualize such data.

Computer Science
teaches
development of
computational tools
to acquire, store,
organize, archive,
analyze and visualize
data

Bioinformatics is referred as
Practical Computer Science
(Bielefeld University, Germany)

Leonard Adleman, Professor of computer
science and of molecular biology at the
University of Southern California
 (RSAAlgorithm - public-key cryptography )
 has argued that life can be equated with
computation
 DNA is both bricks and blueprint - an
engineer's dream
 One gram of DNA can store as much
information as a trillion compact discs

Professor Donald Knuth
Stanford
 Eminent computer scientist, Donald Knuth
of Stanford University has emphasized the
importance of life science and its
connectedness with computer science.

Knuth…..
 Knuth anticipates that the number of
radically new results in pure computer
science is likely to decrease.
 Computer scientists should work on life
science challenges so that they will have
work for the next 500 years.

Gio Wiederhold
Stanford University
 The field of bioinformatics is scary for many
people, because it is a multidisciplinary field ( like
CS earlier), people are worried about where the
positions are and how they can get them
 Bioinformatics is a valuable discipline unless
Universities encourage it, shortage of qualified
people in the field will increase

William Gelbart, Harvard
University
 With our new ways of harvesting massive
data, we have to figure out what to do
with them and how to learn from them.
 (take IT help!)

Future?
 The Indian Bioinformatics market, which is only
2.5% of the global market, has the potential to
capture 5% of the global pie, provided the
government ushers in necessary changes.
According to a report ‘Building Blocks of
Bioinformatics: Human Resource Requirements In
India’, prepared by CII and DIT, the future seems
very bright for the industry since majority of the
Indian Bioinformatics companies are planning
to increase their scale of operations.

Computer to Digital life to life
Can human-made systems be made to possess
properties of life?
 Digital Systems are used, to perform
experiments aimed at revealing the
principles of living systems
 This effort is truly interdisciplinary and
runs the gamut from biology, chemistry
and physics to computer science and
engineering.

Artificial Life to Life…..
 Computational effort concerns the
search for principles of living systems
 Computational experiments consider
life "as it could be"

 The construction of living systems out of non-
living parts is clearly the most ambitious
endeavors: the creation of life using the
classical building blocks of nature (carbon-
based life) and the creation of life using the
same principles but a different medium for
implementation: the computer.

 The former explores the possibility of
"RNA worlds" by attempting to construct
self-replicating molecules;
 The latter (Computer), by simulating
simple populations of self-replicating
entities, examines the abilities and
characteristics of different chemistries in
supporting life-like behavior.
 Thus, both the biochemical and the
computational approaches seek to shed
light on the compelling questions of life.

 Many problems in life science have
algorithmic aspects.
 Among those, the {protein folding
problem} is one
 Proteins are polymer chains consisting of
monomers of twenty different kinds, which
tend to {fold}, to form a very specific and
stable geometric pattern, known as the
protein's {native state}

 Human diseases are linked to specific genes
 Majority of traits and diseases appear to be
{polygenic}, in that they involve the
complex interactions, as in a many-input
Boolean circuit, of many genes.

Human Body as an
Information Processing
Machine?
 Information/ Data
1. Nucleotides (4)
2. Amino Acids (20 or 22)
3. Proteins?
4. DNA (3GB Space~3 billion Base Pairs)
5. Cell

Computation in Human Body
 Folding
 Pattern
 Protein Synthesis
 And such other processes

Life Science Vs Computer
Science
 Life Science is frustratingly holistic?
 It emphasizes the importance of the whole
and the interdependence of its parts like in
CS

Life Science Vs Computer Science
 Computer science has provided highly
useful tools for collecting,
exchanging and analyzing data
Modeling and simulation of
Data
 Finding the right data structure or
algorithm can give answers to life
science problems

Life Science Vs Computer
Science
 Computer science algorithms made it
possible to put together a vast amount of data
from sequencing machines when the
human genome was sequenced.
 Computer science’s computational
paradigm has shaped new
modes of inquiry in life
sciences

HIV-1 Protease/Inhibitor Complex
A79285 (Difluoroketone)


EMBL-Bank DNA Sequences
UniProt Protein Sequences
EMSD Macromolecular
Structure Data
Array-Express
Microarray
Expression Data
EnsEMBL Human Genome
Gene Annotation

Molecular medicine
 The human genome has profound effect on the fields of biomedical
research and clinical medicine. Every disease has a genetic component.
 This may be inherited (as is the case with an estimated 3000-4000
hereditary disease including Cystic Fibrosis and Huntingtons disease)
or a result of the body's response to an environmental stress which
causes alterations in the genome (eg. cancers, heart disease, diabetes.).
 From Human Genome Project Data Base we can search for the genes
directly associated with different diseases and understand the
molecular basis of these diseases more clearly.
 This new knowledge of the molecular mechanisms of disease will
enable better treatments, cures and even preventative tests to be
developed.

Personalized medicine
 Clinical medicine will become more personalized with the
development of the field of pharma-co-genomics.
 This is the study of how an individual's genetic inheritance affects the
body's response to drugs.
 At present, some drugs fail to make it to the market because a small
percentage of the clinical patient population show adverse affects to a
drug due to sequence variants in their DNA.
 As a result, potentially life saving drugs never makes it to the
marketplace.
 Today, doctors have to use trial and error to find the best drug to treat a
particular patient as those with the same clinical symptoms can show a
wide range of responses to the same treatment.
 In future, doctors will be able to analyse a patient's genetic profile and
prescribe the best available drug therapy and dosage from the
beginning.

Preventative medicine
 With the specific details of the genetic mechanisms of
diseases being unraveled, the development of diagnostic
tests to measure a persons susceptibility to different
diseases may become a distinct reality.
 Preventative actions such as change of lifestyle or having
treatment at the earliest possible stages when they are more
likely to be successful, could result in huge advances in
our struggle to conquer disease.

Gene therapy
 In the not too distant future, the potential for using genes
themselves to treat disease may become a reality.
 Gene therapy is the approach used to treat, cure or even
prevent disease by changing the expression of a persons
genes.
 Currently, this field is in its infantile stage with clinical
trials for many different types of cancer and other diseases
ongoing.

Drug development
 At present all drugs on the market target only about 500
proteins.
 With an improved understanding of disease mechanisms
and using computational tools to identify and validate new
drug targets, more specific medicines that act on the cause,
not merely the symptoms, of the disease can be developed.
 These highly specific drugs promise to have fewer side
effects than many of today's medicines.

Microbial genome
applications
 Microorganisms are ubiquitous, that is they are found everywhere.
They have been found surviving and thriving in extremes of heat,
cold, radiation, salt, acidity and pressure.
 They are present in the environment, our bodies, the air, food and
water. Traditionally, use has been made of a variety of microbial
properties in the baking, brewing and food industries.
 The arrival of the complete genome sequences and their potential to
provide a greater insight into the microbial world and its capacities
could have broad and far reaching implications for environment,
health, energy and industrial applications.
 By studying the genetic material of these organisms, scientists can
begin to understand these microbes at a very fundamental level and
isolate the genes that give them their unique abilities to survive under
extreme conditions.

Waste cleanup
 Deinococcus radiodurans is known as the world's toughest
bacteria and it is the most radiation resistant organism
known.
 Scientists are interested in this organism because of its
potential usefulness in cleaning up waste sites that contain
radiation and toxic chemicals.

Climate change Studies
 Increasing levels of carbon dioxide emission,
mainly through the expanding use of fossil fuels
for energy, are thought to contribute to global
climate change.
 One method of doing so is to study the genomes of
microbes that use carbon dioxide as their sole
carbon source.

Alternative energy sources
 Scientists are studying the genome of the microbe
Chlorobium tepidum which has an unusual
capacity for generating energy from light

Bio-Technology
 The archaeon Archaeoglobus fulgidus and the bacterium Thermotoga
maritima have potential for practical applications in industry and
environmental remediation.
 These microorganisms thrive in water temperatures above the boiling
point and therefore may provide knowledge of heat-stable enzymes
suitable for use in industrial processes.
 Other industrially useful microbes include, Corynebacterium
glutamicum which is of high industrial interest as a research object
because it is used by the chemical industry for the biotechnological
production of the amino acid lysine.

Contd…
 The substance is employed as a source of protein in animal nutrition.
Lysine is one of the essential amino acids in animal nutrition.
Biotechnologically produced lysine is added to feed concentrates as a
source of protein, and is an alternative to soybeans or meat and
bonemeal.
 Xanthomonas campestris pv. is grown commercially to produce the
exopolysaccharide xanthan gum, which is used as a viscosifying and
stabilising agent in many industries. Lactococcus lactis is one of the
most important micro-organisms involved in the dairy industry, it is a
non-pathogenic rod-shaped bacterium that is critical for manufacturing
dairy products like buttermilk, yogurt and cheese.
 This bacterium, Lactococcus lactis ssp., is also used to prepare pickled
vegetables, beer, wine, some breads and sausages and other fermented
foods. Researchers anticipate that understanding the physiology and
genetic make-up of this bacterium will prove invaluable for food
manufacturers as well as the pharmaceutical industry, which is
exploring the capacity of L. lactis to serve as a vehicle for delivering
drugs.

Antibiotic resistance
 Scientists have been examining the genome of
Enterococcus faecalis-a leading cause of bacterial infection
among hospital patients.
 They have discovered a virulence region made up of a
number of antibiotic-resistant genes that may contribute to
the bacterium's transformation from a harmless gut
bacteria to a menacing invader.
 The discovery of the region, known as a pathogenicity
island, could provide useful markers for detecting
pathogenic strains and help to establish controls to prevent
the spread of infection in wards.

Forensic analysis of
microbes
 Scientists used their genomic tools to help
distinguish between the strains of Bacillus
anthraces that was used in the summer of 2001
terrorist attack in Florida with that of closely
related anthrax strains.

The reality of bio-weapon
creation
 Scientists have recently built the virus poliomyelitis using
entirely artificial means. They did this using genomic data
available on the Internet and materials from a mail-order
chemical supply.
 The research was financed by the US Department of
Defense as part of a bio-warfare response program to
prove to the world the reality of bio-weapons.
 The researchers also hope their work will discourage
officials from ever relaxing programs of immunization.
This project has been met with very mixed feelings

Evolutionary studies
 The sequencing of genomes from all three
domains of life, eukaryota, bacteria and archaea
means that evolutionary studies can be performed
in a quest to determine the tree of life and the last
universal common ancestor.

Crop improvement
 Comparative genetics of the plant genomes has shown that
the organisation of their genes has remained more
conserved over evolutionary time than was previously
believed.
 These findings suggest that information obtained from the
model crop systems can be used to suggest improvements
to other food crops.
 At present the complete genomes of Arabidopsis thaliana
(water cress) and Oryza sativa (rice) are available.

Insect resistance
 Genes from Bacillus thuringiensis that can control a
number of serious pests have been successfully transferred
to cotton, maize and potatoes.
 This new ability of the plants to resist insect attack means
that the amount of insecticides being used can be reduced
and hence the nutritional quality of the crops is increased.

Improve nutritional quality
 Scientists have recently succeeded in transferring genes
into rice to increase levels of Vitamin A, iron and other
micronutrients.
 This work could have a profound impact in reducing
occurrences of blindness and anaemia caused by
deficiencies in Vitamin A and iron respectively.
 Scientists have inserted a gene from yeast into the tomato,
and the result is a plant whose fruit stays longer on the vine
and has an extended shelf life.

Development of Drought
resistance varieties
 Progress has been made in developing cereal varieties that
have a greater tolerance for soil alkalinity, free aluminum
and iron toxicities.
 These varieties will allow agriculture to succeed in poorer
soil areas, thus adding more land to the global production
base.
 Research is also in progress to produce crop varieties
capable of tolerating reduced water conditions.

Veterinary Science
 Sequencing projects of many farm animals including cows,
pigs and sheep are now well under way in the hope that a
better understanding of the biology of these organisms will
have huge impacts for improving the production and health
of livestock and ultimately have benefits for human
nutrition.

Comparative Studies
 Analyzing and comparing the genetic material of different species is an
important method for studying the functions of genes, the mechanisms
of inherited diseases and species evolution.
 Bioinformatics tools can be used to make comparisons between the
numbers, locations and biochemical functions of genes in different
organisms.
 Organisms that are suitable for use in experimental research are termed
model organisms.
 They have a number of properties that make them ideal for research
purposes including short life spans, rapid reproduction, being easy to
handle, inexpensive and they can be manipulated at the genetic level.
 An example of a human model organism is the mouse.
 Mouse and human are very closely related (>98%) and for the most
part we see a one to one correspondence between genes in the two
species.

application_of_bioinformatics_in_various_fields.ppt

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