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Rapid advances in bioinformatics are providing new hopes to patients of life threatening diseases. Gene chips will be able to screen heart attack and diabetics years before patients develop symptoms. In near future, patients will go to a doctorâ„¢s clinic with lab- on- a- chip devices. The device will inform the doctor in real time if the patientâ„¢s ailment will respond to a drug based on his DNA. These will help doctors diagnose life-threatening illness faster, eliminating expensive, time-consuming ordeals like biopsies and sigmoidoscopies. Gene chips reclassify diseases based on their underlying molecular signals, rather than misleading surface symptoms. The chip would also confirm the patientâ„¢s identity and even establish paternity.
Bioinformatics is an inter disciplinary research area. It is a fusion of computing, biotechnology and biological sciences. Bioinformatics is poised to one of the most prodigious growth areas in the next to decades. Being the interface between the most rapidly advancing fields of biological and computational sciences, it is immense in scope and vast in applications.
Bioinformatics is the study of biological information as it passes from its storage site in the genome to the various gene products in the cell. Bioinformatics involves the creation and computational technologies for problems in molecular biology. As such ,it deals with methods for storing, retrieving and analyzing biological data, such as nuclei acid (DNA/RNA)and protein sequence, structures, functions, path ways and interactions. The science of Bioinformatics, which is the melding of molecular biology with computer science is essential to the use of genomic information in understanding human diseases and in the identification of new molecular targets of drug discovery. New discoveries are being made in the field of genomics, an area of study which looks at the DNA sequence of an organism in order to determine which genes code for beneficial traits and which genes are involved in inherited diseases.
If you are not tall enough, the stature could be altered accordingly. If you are weak and not strong enough, your physique could be improved. If you think this is the script for a science fiction movie, you are mistaken. It is the future reality.
2. EVOLUTION OF BIOINFORMATICS
DNA is the genetic material of organism. It contains all the information needed for the development and existence of an organism. The DNA molecule is formed of two long polynucleotide chains which are spirally coiled on each other forming a double helix. Thus it has the form of spirally twisted ladder. DNA is a molecule made from sugar, phosphate and bases. The bases are guanine (G), cytosine©adenine(A) and thiamine(T).Adenine pairs only with Thiamine and Guanine pairs only with Cytosine. The various combinations of these bases make up with DNA. That is; AAGCT, CCAGT, TACGGT etc. An infinite number of combinations of these bases is possible. And then the gene is a sequence of DNA that represents a fundamental unit of heredity. Human genome consists of approximately 30,000 genes, containing approximately 3 billion base pairs.
Currently, scientists are trying to determine the entire DNA sequence of various living organisms. DNA sequence analysis could identify genes, regulatory sequences and other functions. Molecular biology, algorithms, and computing have helped in sequencing larger portions of genomics of several species. Sequence is the determination of the order of nucleotides in a DNA as also the order of amino acids in a protein. Sequence analysis, which is at the core of bioinformatics, enables function identification of genes.
The human found in every cell of a human being consists of 23pairs of chromosomes. These chromosomes constitute the 3 billion letters of chemical code that specify the blue print for a human being. Human Genome Project, one of the best known project and implimentations in the world. The world Human Genome Project, a vast endeavor aimed at reading this entire DNA code will completely transform biology, medicine and biotechnology. Using this entire code all 30,000 human genes will be identified; all 5000 inherited diseases will become diagnosable and potentially curable; and drug design will be completely transformed. The Genome Project focuses on two main objective: mapping-pinpointing the genomic location of all genes and markers; and DNA sequencing-reading the chemical "text" of all the genes and their intervening sequences. DNA sequences are entered in to large data bases, where they can be compared with the known genes, including inter-species comparisons. The explosion of publicly available genomic information resulting from the Human Genome Project has precipitated the need for bioinformatics capabilities.
Determination of genome organization and gene regulation will promote the understanding of how humans develop from single cells to adults, why this process some times goes wrong, and the changes that take place as people age. Bioinformatics finds applications in medicine for recommending individually tailored drugs based on an individual's profile. It helps to identify a specific genetic sequence that is responsible for a particular disease, its associated protein, and protein function. For curing the disease a new drugs can be developed.
3. HUMAN ELECTRONICS
The nucleus is the most obvious organelle in the human cell. Within the nucleus is the DNA responsible for providing the cell with its unique characteristics. The DNA is similar in every cell of the body, but depending on the specific cell type; some genes may be turned on or off-that is why a liver cell is different from a muscle cell, and a muscle cell is different from a fat cell. About 99.9% of the sequence is identical between any two people. But because the small percentage of DNA that differs can relate to an individualâ„¢s disease. Scientists are comparing sequence using DNA chips from healthy people and those from patients with a specific disease to help identify genetic targets for drug discovery information about genetic variation can help to predict which patients are likely to benefit from specific drugs
The most significant and the biggest application of DNA chips is the use of DNA micro arrays for expression profiling. In expressions profiling the chip controls how different parts of the genes turned on or off to create certain types of cells. If the gene is expressed in one way, it may result in normal muscle, for instance. If it is expressed in another way, it may result in a tumor. By comparing these different expressions, researchers hope to discover ways to predict and perhaps to prevent diseases.
Electronic circuit can be incorporated in the chip to detect various states of DNA. DNA carries an electric charge. That charge can be read on the chip, just like cells on a memory array. This DNA chip would like to diagnose life-threatening bacterial infections.
In DNA the medium is a chain of two units (phosphate & ribose), and the most easily recognizable message is provided by a sequence of letters (bases) attached to the chain. The DNA has two sequences of letters wrapped in the form of a double helix. The DNA has two sequences of letters wrapped around each other in the form of a double helix. One is the complement of other, so that the sequence of one string (strand) can be inferred from the sequence of other. The DNA sequence of bases encodes 20 amino acids. Under instructions received from DNA, amino acids join together in the same order as they are encoded in DNA to form proteins. Chains of amino acids, which fold in complicated ways, play a major role in determining how we interact with the environment.
Genomic information is revolutionizing life sciences. The quest for under standing how genetic factors contribute to human disease is gathering speed. The 46 human chromosomes house almost three billion base pairs of DNA that contain 30,000 to 40,000 protein-coding genes. Using bioinformatics find out how genes contribute to diseases that have a complex pattern of inheritance, such as diabetics, asthma, and mental illness. No one gene can tell whether a person has a disease or not. A number of genes may make a subtle contribution to a person's susceptibility to a disease. Gene may also affect how a person reacts to the environment. As the entire human genome is too big a sequence on its own, sequencing and reading a genome demand heavy computational resources.
DNA control via RF signal
Researchers at MIT have moved a step closer towards integrating electronics and biological functions. They have been able to control biomolecules using RF energy and nanocrystal antena. They remotely controlled the behaviour of DNA, the basic building block of humans and other forms of life, causing it to switching from one state to another at will.
An electronic interface to the biomolecule was created. RF magnetic field was inductively coupled to a 1nm long nanocrystal antenna linked covalently to a DNA molecule. The inductive coupling, ie; the transfer of energy to the nanocrystal energy, incresed the local temperature the bound DNA, allowing the change of state to take place, while leaving molecules surrounding the DNA relatively un affected. The swithing was fully reversible, as dissolved molecules dissipated the heat in less than 50 picoseconds. Thus RF signal generated out side the body can control changes in the DNA. THE signal used in this experiment was 1 GHz
4. CHIP ELECTRONICS
Chip electronics can be divided into two.
2. Clinical chip
Biochip is an IC whoâ„¢s electrical and logical functions are performed by protein molecules appropriately manipulated. Advances in molecular biology and semiconductor fabrication have resulted in new formats for hybridization arrays. Instead of these being based on a membrane or a glass slide platforms these arrays several electrodes covered by a thin layer of agarose coupled with affinity moiety. Each micro electrode is capable of generating a controllable electric current that can be used to draw biological samples, reagents and probes to specify locations on the chip surface. The number of genes covered by these arrays depends on the number of electrodes made within the area of that array.
Biochips can be mainly classified into two based on the applications:
1. Internal biochips
2. External biochips
Applications of internal biochips are
1. Glucose measurement
2. Brain surgery for Parkinsonâ„¢s disease
3. Cochlear implant
4. Eye implant
5. Personal identification
Applications of external biochips are
1. lab on a chip
2. mass spectrometry
APPLICATION OF INTERNAL BIOCHIPS
1. GLUCOSE MEASUREMENT
Nowadays diabetics measure the level of sugar glucose in their blood by using a skin prick and a hand held blood test and medicate them with insulin. The disadvantage of this simple system is that the need to draw blood makes the diabetics not to test the sugar levels themselves as often as they could.
By using Biochips the measurement can be done in a much simpler way. The chips are of size less than an uncooked grain of rice can be injected under the skin. It sense the glucose level and send the result back out by radio frequency communication.
Fig.1. S4MS chip
The light emitting diode (LED) starts off the detection process. The light that it produces hits a fluorescent chemical. The property of the fluorescent chemical is to absorb the incoming light and re-emit the light at a longer wavelength. The longer wavelength of light is then detected and the result is send to a control panel outside the body.
Glucose is detected because the sugar reduces the amount of light the fluorescent chemical reemits. The more the glucose, the less the light is detected.
The biochip used in glucose sensing is S4MS chip. In this chip, the LED is kept in a sea of fluorescent molecules. The LED used is almost 40 times less powerful than the tiny power on buttons on a computer keyboard. The low power requirement mean that energy can be supplied from outside by a process called induction. The fluorescent detection itself does not consume any chemicals or proteins, so device is self sustaining.
2. BRAIN SURGERY FOR PARKINSONâ„¢S DISEASE
Parkinsonâ„¢s disease is caused by a brain messenger dopamine, which is a product of dying brain cells. This disease causes uncontrolled movements or tremors on body parts.
Drug therapy for Parkinsonâ„¢s disease aims to replace dopamine but the drugs effect wear off after some time. This causes the erratic movements coming back to the patients.
Activa implant is a biochip which uses high frequency electrical pulses to reversibly shut off the thalamus. These chips turn off brain signals that cause the uncontrolled movements or tremors. The implantation surgery is far simpler. Electrodes will be entered in to the thalamus region whose extension is connected to the pulse generator placed near the chest. The pulse generator generates pulses according to the heart beat of the patient.
If there are any post operative problems the simulator (pulse generator) can be simply turned off.
FIG.2. ACTIVA IMPLANT
3. COCHLEAR IMPLANT
Hearing aids used in present days are glorified amplifiers, but the cochlear implant is for patients who have lost the hair cells that detect sound waves. For these individuals no amount of amplification is enough.
Fig.3. cochlear implant
The cochlear implant delivers electrical pulses directly to the nerve cells in the cochlea, the spiral shaped structure that translates sound into nerve pulses. In normal hearing individuals, sound wave set up vibrations in the walls of the cochlea, and hair cells detect these vibrations.
High frequency noises vibrate the base of the cochlea, while low frequency notes vibrate near the top of the spiral.
The cochlear implant does the job of the hair cells. It splits the frequencies of incoming noises into a number of channels and then stimulates the appropriate part of cochlea.
Increasing the number of channels will improve sound perception. But speech is perceived in an area of the cochlea only 14 mm long and spacing the electrodes to close to each other causes signals to bleed from one channel to another. This causes a broad version of hearing.
4. EYE IMPLANT
Vision occurs as the light reflected from a body is received by photoreceptors, the light sensing cells at the back of the eye. Blindness occurs if the photoreceptors are lost in retinitis pigmentosa, a genetic disease and in related macular degeneration.
The chip used in eye implant does the function of photoreceptors. The chip will be at least ten times smaller than the thickness of the human hair with an area of 1mm2. There will be a camera mounted on a pair of glasses. The camera will detect and encode the scene and then send it into the eye as a laser pulse. The laser will also provide the energy to drive the chip. The energy required for stimulating a nerve cell in the eye is almost 100 times lower than that required in stimulating a nerve cell in an ear.
Fig.4. size of a chip implanted in eye (compared with a penny)
5. PERSON IDENTIFICATION
Biochips when implanted into human body can have an identification number, and all the details about that person. This can help agencies to locate lost children, soldiers and Alzheimerâ„¢s patient. Biochips are widely used in identification of criminals and terrorists in America.
APPLICATIONS OF EXTERNAL CHIPS
1. LAB ON A CHIP
Biochips scan, process biological data very rapidly. The technology is commonly known as Ëœlab on a chipâ„¢. The idea of a cheap and reliable computer chip look alike that performs thousands of biological reactions is very attractive to drug developers. Because these chips automate highly repetitive laboratory tasks by replacing cumbersome equipment with miniaturized microfluidic assay chemistries. Biochips are able to provide ultrasonic detection methodologies at significantly lower costs per assay than traditional and also amount of space.
Applications of lab on a chip are basically two
ÃƒËœ For the detection of mutations in specific genes as diagnostic markers on the onset of a particular disease. E.g.: HIV gene chip
ÃƒËœ To detect the differences in gene expression levels in cells those are diseased versus those that are healthy.
E.g.: cancer studies
2. MASS SPECTROMETRY
Mass spectrometry determines molecular structures from ionized samples of materials. Biochips can be used to perform mass spectrometry and researches are going in that area. This can help in saving much space and time in laboratories.
2. CLINICAL CHIPS
A decade ago, an eight-year old kid jumped from his swing set and landed flat, shattering a leg bone where most kids would have sprained an ankle. An X-ray revealed this problem. Where there should have been hard bone, a soft tumour was present. The kid needed a precise diagnosis. If the cancer was aggressive, it needed immediate treatment with the powerful but toxic drug 'adriamycin'. If the tumour was growing slowly, doctors had the time to try out weaker but safer drugs.
A biopsy was inconclusive. Like many paediatric bone tumours, the kidâ„¢s tumour was a small, round blue- cell tumour. The doctor had a problem treating the kid. As adriamycin could cause serious heart damage, doctors weren't willing to give it to the kid. Of all blue cell tumours spreads aggressively enough to require this potentially deadly medicine. Doctors hoped that a less toxic medicine will do and gave the same to the kid, resulting in the death of the kid just after six months. Today, rapid advances in bioinformatics are providing new hopes to such patients. The new technology enables doctors to proceed straight to genetic codes that instruct tumours to grow, finding invisible molecular signals that differentiate cancers as well as a host of other deadly diseases.
The key to this life saving, cost effective diagnostic power is a tiny glass chip peppered with DNA strips, called the gene chip. Today, 60% of gene chips are used for are research purposes, where these are speeding up drug design and helping researchers to mine genomic data bases.
Gene chip will be able to screen diseases like heart attack and diabetics years before patients develop symptoms. These will help doctors diagnose life-threatening illness faster, eliminating expensive, time-consuming ordeals like biopsies and sigmoidoscopies, or simple blood, saliva, stool, or urine tests. Gene chips reclassify diseases based on their underlying molecular signals, rather than misleading surface symptoms.
5. FUTURE DEVELOPMENT
Researchers are working on Bioinformatics that will perform fundamental body changes apart from customizing looks of the people. If you arenâ„¢t born perfect, any disease and deformity, you need not despair. Because rapid advances in bioinformatics are providing new hopes to such patients. Researchers are going on in the field of` biological computersâ„¢ hybrid machine like science fiction cyborg which would blend organics and electronics in a single machine. The information processing and storage capabilities of organic molecules are far more superior than the devices that human have been able to create out of silicon.
A few specific areas that fall within the scope of bioinformatics are as follows:
1.Sequence assembly â€œ
The genome of an organisation is assembled from thousands of fragments, which must be correctly 'switched' together. this process requires sophisticated computer- based methods and is carred out by bioinformatics specialists.
2.Sequence (gene) analysis â€œ
Once the DNA sequence of a fragment of the genome is determined, the next step is the understanding of the function of the gene. This involves various analyses, which are carried out by high- powered computing and specialised software. Many would concider this activity as the most important area of focus within bioinformatics.
A relatively new area, proteomics studies not the entire genome, but the portion of the genome that is expressed in particular cells. This involves the collections between patterns of expression of the genes and a particular disease state to determine likely targets for drug and/or gene therapy. Bioinformatics specialists work closely with scientists to accomplish the same.
Alterations in the genome at specific positions can be associated with particular disease states, reduced or increased sensitivity to particular drugs, or with side effects to those medications. Such databases are rapidly evolving, and are likely to play an important role in the future drug development efforts and in the design of clinical trails. Bioinformatics experts are at the forefront to collect, analyse and apply this crucial data.
Days aren't far off when beauty saloons will perform fundamental body changes apart from customizing looks of the people. If you aren't born perfect, free from any diseases and deformity, you need not despair. Rapid advances in bioinformatics are providing new hopes to such patients. At the first sign of physical defect or deformity, people will shop around for a better and stronger organically grown heart, brain, or kidney, as the case may be. With bioinformatics man kind will be able to prolong its life or , even live forever.
Ã‚Â· Electronics For You-February 2003- page(36-42)
Ã‚Â· Information Technology-June 2003-page(26-29)
1. INTRODUCTION 1
2. EVOLUTION OF BIOINFORMATICS 2
3. HUMAN ELECTRONICS 4
4. CHIP ELECTRONICS 7
1. BIOCHIP 9
Ã‚Â· Internal biochips
Ã‚Â· External biochips
2. CLINICAL CHIP 16
5. FUTURE DEVELOPMENT 18
6. CONCLUSION 20
7. REFERENCE 21
I express my sincere gratitude to Dr.Nambissan, Prof. & Head, Department of Electrical and Electronics Engineering, MES College of Engineering, Kuttippuram, for his cooperation and encouragement.
I would also like to thank my seminar and presentation guide Mrs. Nafeesa K. (Lecturer, Department of EEE), Asst. Prof. Gylson Thomas. (Staff in-charge, Department of EEE) for their invaluable advice and wholehearted cooperation without which this seminar and presentation would not have seen the light of day.
Gracious gratitude to all the faculty of the department of EEE & friends for their valuable advice and encouragement.
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Bioinformatics was applied in the creation and maintenance of a database to store biological information at the beginning of the "genomic revolution", such as nucleotide and amino acid sequences. Development of this type of database involved not only design issues but the development of complex interfaces whereby researchers could both access existing data as well as submit new or revised data.
In order to study how normal cellular activities are altered in different disease states, the biological data must be combined to form a comprehensive picture of these activities. Therefore, the field of bioinformatics has evolved such that the most pressing task now involves the analysis and interpretation of various types of data, including nucleotide and amino acid sequences, protein domains, and protein structures. The actual process of analyzing and interpreting data is referred to as computational biology. Important sub-disciplines within bioinformatics and computational biology include:
a) the development and implementation of tools that enable efficient access to, and use and management of, various types of information. b) the development of new algorithms (mathematical formulas) and statistics with which to assess relationships among members of large data sets, such as methods to locate a gene within a sequence, predict protein structure and/or function, and cluster protein sequences into families of related sequences.
Bioinformatics is the application of information technology and computer science to the field of molecular biology. The term bioinformatics was coined by Paulien Hogeweg in 1979 for the study of informatic processes in biotic systems. Its primary use since at least the late 1980s has been in genomics and genetics, particularly in those areas of genomics involving large-scale 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 analysis of biological data. Over the past few decades rapid 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. Common 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 primary goal of bioinformatics is to increase our understanding of biological processes. What sets it apart from other approaches, however, is its focus on developing and applying computationally intensive techniques (e.g., pattern recognition, data mining, machine learning algorithms, and visualization) to achieve this goal. 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 association studies and the modeling of evolution.
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