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Chapter 2
Bioinformatics is the application of complex statistics and automata
computation to the field of molecular biology. Bioinformatics was first
introduced by Paulien Hogeweg and Ben Hesper in 1978 for the biotic
systems study. [26, 27, and 28] its primarily use since late 1980s has been in
genomics and genetics, predominantly in those areas of genomics involving
huge amount of DNA sequencing.

Bioinformatics now entails the creation and advancement of databases,

algorithms, computational and statistical techniques and theory to solve
formal and practical problems arising from the management and study of
biological information. Over the last few years fast developments in genomic
and other molecular research technologies and developments in information
technologies have combined to produce a tremendous amount of information
related to molecular biology.

It is the name given to these mathematical and computing approaches used

to glean understanding of biological processes. regular activities in
bioinformatics include mapping and analyzing DNA and protein sequences,
aligning different DNA and protein sequences to compare them and creating
and viewing 3-D models of protein structures. The principal object of
bioinformatics is to enhance the accepting of biological processes.

What sets it apart from other approaches, however, is its focus on developing
and applying computationally severe techniques (e.g., pattern recognition,
data mining, machine learning algorithms, and visualization) to achieve this
purpose. Major research efforts in the field include sequence alignment, gene
finding, genome assembly, drug design, drug discovery, protein structure
alignment, protein structure prediction, prediction of gene expression and
protein-protein interactions, genome-wide relationship studies and the
modeling of progress.

Computational biology and bioinformatics are multidisciplinary areas,

involving researchers from different area of expertise, including (but in no
means limited to) complex statistics, computer science, physics,
biochemistry, genetics, molecular biology and mathematics. The goal of
these two fields is as follows Bioinformatics: in general refers to the field
concerned with the collection and storage of biological information.

All matters concerned with biological databases are considered

bioinformatics. Computational biology: Refers to the characteristic of
developing algorithms and statistical models essential to analyze biological
data through the aid of computers. 2.2

Applications of Bioinformatics Bioinformatics is the application of Information

Technology it uses in Biology for the data storage, data warehousing and
analyzing the DNA sequences. In Bioinformatics awareness of many subjects
are required like biology
<http://www.roseindia.net/bioinformatics/applications.shtml>, mathematics,
computer science, laws of physics & chemistry, and of course good
knowledge of IT to analyze biotech data.

Bioinformatics is not limited to the computing data, but in reality it can be

used to solve many complex biological problems and find out how living
things naturally works. It is the comprehensive application of mathematics
(e.g., probability and statistics), science (e.g., biochemistry), and a core set
of problem-solving methods (e.g., computer algorithms) to the
understanding of living systems
<http://www.roseindia.net/bioinformatics/applications.shtml>.

2.3 Gene Genes are functional units of DNA that contain the instructions for
making proteins or RNA. Genes also act as units of heredity, transferring the
same instructions from parent to offspring. The nature, structure, and
regulation of genes have been a central topic of scientific research for more
than 100 years.

Every gene consists of a linear sequence of bases in a nucleic acid molecule.

Genes are specified by the sequence of bases in DNA in prokaryotic,
archaeal, and eukaryotic cells, and in DNA or ribonucleic acid (RNA) in
prokaryotic or eukaryotic viruses. The ultimate expressions of gene function
are the formation of structural and regulatory RNA molecules and proteins.

These macromolecules carry out the biochemical reactions and provide the
structural elements that make up cells. Deoxyribonucleic acid (DNA), Nucleic
acid, Ribonucleic acid (RNA), Virus, A modern working definition of a gene is
"a locatable region of genomic sequence, corresponding to a unit of
inheritance, which is associated with regulatory regions, transcribed regions,
and or other functional sequence regions ".

Colloquial usage of the term gene (e.g. "good genes, "hair color gene") may
actually refer to an allele a gene is the basic instruction, a sequence of
nucleic acid (DNA or, in the case of certain viruses RNA), while an allele is
one variant of that gene. Thus, when the mainstream press refers to "having"
a "gene" for a specific trait, this is generally inaccurate.

In most cases, all people would have a gene for the trait in question, but
certain people will have a specific allele of that gene, which results in the
trait variant. In the simplest case, the phenotypic variation observed may be
caused by a single letter of the genetic code a single nucleotide
polymorphism. 2.4 Gene Expression Profile Gene expression is the process by
which information from a gene is used in the synthesis of a functional gene
product.

These products are often proteins, but in non-protein coding genes such as
ribosomal RNA (rRNA) genes or transfer RNA (tRNA) genes, the product is a
functional RNA. The process of gene expression is used by all known life-
eukaryotes (including multicellular organisms), prokaryotes (bacteria and
archaea) and viruses to generate the macromolecular machinery for life.

Several steps in the gene expression process may be modulated, including

the transcription, RNA splicing, translation, and post-translational
modification of a protein. Gene regulation gives the cell control over
structure and function, and is the basis for cellular differentiation,
morphogenesis and the versatility and adaptability of any organism.

Gene regulation may also serve as a substrate for evolutionary change, since
control of the timing, location, and amount of gene expression can have a
profound effect on the functions (actions) of the gene in a cell or in a
multicellular organism. In genetics, gene expression is the most fundamental
level at which the genotype gives rise to the phenotype.

The genetic code stored in DNA is "interpreted" by gene expression, and the
properties of the expression give rise to the organism's phenotype Gene
Expression profile Gene expression profiling or microarray analysis has
enabled the measurement of thousands of genes in a single RNA sample.
There are a variety of microarray platforms that have been developed to
accomplish this and the basic idea for each is simple a glass slide or
membrane is spotted or "arrayed" with DNA fragments or oligonucleotides
that represent specific gene coding regions.

Purified RNA is then fluorescently- or radioactively labeled and hybridized to

the slide/membrane. In some cases, hybridization is done simultaneously
with reference RNA to facilitate comparison of data across multiple
experiments. After thorough washing, the raw data is obtained by laser
scanning or auto radiographic imaging.

At this point, the data may then be entered into a database and analyzed by
a number of statistical methods. These profiles can, for example, distinguish
between cells that are actively dividing, or show how the cells react to a
particular treatment. Many experiments of this sort measure an entire
genome simultaneously, that is, every gene present in a particular cell.

DNA Microarray technology measures the relative activity of previously

identified target genes. Sequence based techniques, like serial analysis of
gene expression (SAGE, SuperSAGE) are also used for gene expression
profiling. SuperSAGE is especially accurate and can measure any active
gene, not just a predefined set.

The advent of next-generation sequencing has made sequence based

expression analysis an increasingly popular, "digital" alternative to
microarrays. However, microarrays are far more common, accounting for
7,000 PubMed articles by year 2010. Expression profiling is a logical next
step after sequencing a genome the sequence tells us what the cell could
possibly do, while the expression profile tells us what it is actually doing now.

Genes contain the instructions for making messenger RNA (mRNA), but at
any moment each cell makes mRNA from only a fraction of the genes it
carries. If a gene is used to produce mRNA, it is considered "on", otherwise
"off". Many factors determine whether a gene is on or off, such as the time of
day, whether or not the cell is actively dividing, its local environment, and
chemical signals from other cells. Skin cells, liver cells and nerve cells turn
on (express) somewhat different genes and that is in large part what makes
them different.

Therefore, an expression profile allows one to deduce a cell's type, state,

environment, and so forth. Expression profiling experiments often involve
measuring the relative amount of mRNA expressed in two or more
experimental conditions. This is because altered levels of a specific sequence
of mRNA suggest a changed need for the protein coded for by the mRNA,
perhaps indicating a homeostatic response or a pathological condition.

For example, higher levels of mRNA coding for alcohol dehydrogenase

suggest that the cells or tissues under study are responding to increased
levels of ethanol in their environment. Similarly, if breast cancer cells
express higher levels of mRNA associated with a particular transmembrane
receptor than normal cells do, it might be that this receptor plays a role in
breast cancer. A drug that interferes with this receptor may prevent or treat
breast cancer.

In developing a drug, one may perform gene expression profiling

experiments to help assess the drug's toxicity, perhaps by looking for
changing levels in the expression of cytochrome P450 genes, which may be a
biomarker of drug metabolism. Gene expression profiling may become an
important diagnostic test. Expression profiling provides new information
about what genes do under various conditions. Overall, microarray
technology produces reliable expression profiles.

From this information one can generate new hypotheses about biology or
test existing ones. However, the size and complexity of these experiments
often results in a wide variety of possible interpretations. In many cases,
analyzing expression profiling results takes far more effort than performing
the initial experiments.

Most researchers use multiple statistical methods and exploratory data

analysis before publishing their expression profiling results, coordinating
their efforts with a biostatistician or other expert in microarray technology.
Good experimental design, adequate biological replication and follow up
experiments play key roles in successful expression profiling experiments.
2.5

Cancer Cancer is a term used for diseases in which abnormal cells divide
without control and are able to invade other tissues. Cancer cells can spread
to other parts of the body through the blood and lymph systems. Cancer is
not just one disease but many diseases. There are more than 100 different
types of cancer.

Most cancers are named for the organ or type of cell in which they start for
example, cancer that begins in the colon is called colon cancer; cancer that
begins in basal cells of the skin is called basal cell carcinoma. Cancer types
can be grouped into broader categories. [32, 33, 34] The main categories of
cancer include: Carcinoma - cancer that begins in the skin or in tissues that
line or cover internal organs Sarcoma - cancer that begins in bone, cartilage,
fat, muscle, blood vessels, or other connective or supportive tissue.

Leukemia - cancer that starts in blood-forming tissue such as the bone

marrow and causes large numbers of abnormal blood cells to be produced
and enter the blood. Lymphoma and myeloma - cancers that begin in the
cells of the immune system. Central nervous system cancers - cancers that
begin in the tissues of the brain and spinal cord

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