Bioinformatics is an emerging scientific discipline representing the combined power of Biology, Mathematics, IT, Computer Science and Electronics to solve complex problems in life sciences and particularly in biotechnology.
Electronics and computational techniques are increasingly being used to analyze biological cells to diagnose diseases, discover drugs, and develop methodologies to deliver the drugs inside the human body. Electronic is playing a leading role by way of developing Gene chips, Bio chips, Control of DNA via RF signal and many more.
1. Bio chips: Multi function bio chips allow simultaneous detection of several diseases and point out DNA, Antibodies on a single biochip system.
2. DNA control via RF signal: The RF signal of 1 GHz generated out side the body can control the changes in the DNA (at research stage at MIT).
3. GeneChip: The GeneChip System supports both DNA and RNA analysis. These chip are based on the electrical and electron charges exhibited by the cells of the human body.
In this paper it aimed to show the relevance of electronics in a field of bioinformatics, this paper deals with the analysis of cancer using GeneChip (DNA microarrays). Gene chip are used for Global understanding of abnormal gene expression contributing to malignancy, prediction of drug side effects during preclinical development and toxicology studies, which predicts treatment success or failure.
And the applications go on…..
INTRODUCTION:
Bioinformatics is an integrated multidisciplinary field. It comprises molecular biology (biochemistry, genetics, structural biology etc.), computer science (computational theory, artificial intelligence, machine learning, dynamic programming etc.), physical chemistry (thermodynamics, molecular modeling etc) and mathematics (algorithms, modeling, probabilistic, statistics etc.).It is hard to draw a clear line between the ‘exact disciplines’ of bioinformatics research because this is a broad and fast growing field.
It is widely believed that thousands of genes and their products (i.e., RNA and proteins) in a given living organism function in a complicated and orchestrated way that creates the mystery of life.
Cancers are caused through gene mutations and other types of chromosomal or molecular abnormalities. Gene mutations in cancers invariably lead to alterations of gene expression patterns with respect to normal cellular counterparts.An overview of genes and their expression profiles possibly involved in cancer is essential to gain a detailed understanding of molecular carcinogenesis. Molecular data may be of clinical use to improve cancer diagnosis i.e. to predict appropriate treatment selection.
THE MOLECULAR DIAGNOSTICS OF CANCERS:
Molecular diagnostics nowadays explore an astonishingly wide variety of nucleic acid sources for tumour diagnosis. DNA or RNA extracted from bone marrow can be used to detect specific chromosomal translocations in leukemia by sensitive polymerase chain reaction (PCR). Sensitive molecular techniques allow us to detect tumour cells in urine. Since the Human Genome Project now maps thousands of genes and their sequences, a wealth of genetic information has become available for potential diagnostic use. However, many molecular methods may be too cumbersome to survey all relevant molecular markers in a tumour biopsy. New techniques may help to overcome this limitation.
DNA MICROARRAY (GENOME CHIP):
It is widely believed that thousands of genes and their products (i.e., RNA and proteins) in a given living organism function in a complicated and orchestrated way that creates the mystery of life. However, traditional methods in molecular biology generally work on a "one gene in one experiment" basis, which means that the throughput is very limited and the "whole picture" of gene function is hard to obtain.
1) Identification of sequence (gene / gene mutation).
2) Determination of expression level (abundance) of genes.
MONITORING THE GENOME ON A CHIP:
A simple cDNA array experiment has five basic steps
1 .The target cDNA is spotted or printed onto a substrate.
2. The sample RNA is isolated to get good data.
3. The cDNA is synthesized, a procedure that also involves labeling it for later detection.
4. The labeled probe cDNA is hybridized to target the cDNA on the substrate.
5. Finally the hybridization results are imaged and analyzed.
Monitoring gene expression lies at the heart of a wide variety of medical and biological research projects, including classifying diseases, understanding basic biological processes, and identifying new drug targets. Until recently, comparing expression levels across different tissues or cells was limited to tracking one or a few genes at a time.
Standard eukaryotic gene expression assay
The basic concept behind the use of GeneChip arrays for gene expression is simple:
labeled cDNA or cRNA targets derived from the mRNA of an experimental sample are hybridized to nucleic acid probes attached to the solid support. By monitoring the amount of label associated with each DNA location, it is possible to infer the abundance of each mRNA species represented. Although hybridization has been used for decades to detect and quantify nucleic acids, the combination of the miniaturization of the technology and the large and growing amounts of sequence information, have enormously expanded the scale at which gene expression can be studied.
Data Acquisition and Basic Analysis:
Analyzing GeneChip gene expression experiments can be done using software such as (MAS), ArraVision, Array stat etc. MAS tool manages both the acquisition and processing of GeneChip-generated data, providing a seamless transition from assay performance to data analysis.
Comparison Analysis:
Most gene expression studies involve comparing data from two or more arrays. To facilitate these comparisons, MAS enables users to designate one of their arrays as a baseline and another as experimental.
ANALYSES OF CANCER WITH DNA MICROARRAYS:
In cancers, the diagnostic material usually consists of RNA samples extracted from tumours of interest, which are labeled for hybridization on chips to study large-scale gene expression profiles. Many protocols foresee a comparative and competitive hybridization of tumour RNA samples on the chip against normal or reference RNA labeled with different colours. As with more traditional molecular diagnostic methods, the enrichment of tumour cells is important. This can be achieved by ‘virtual dissection’ of chip data in a computer.
Gene chip
Figure: Schematic representation of a DNA microchip
The major application of microchips falls into three categories:
1. Gene Expression Profiling: RNA is extracted from tumour samples and hybridized to the microarray to assess simultaneously and in a single experiment the expression of thousands of genes within the sample.
2. Genotyping: Genomic DNA from an individual is tested for hundreds or thousands of genetic markers in a single hybridization. This will yield a genetic fingerprint, which in turn may be linked to the risk of developing single gene disorders or particular common complex diseases.
3. DNA Sequencing: Sequence variations of specific genes can be screened in a test DNA sample, thereby greatly increasing the scope for precise molecular diagnosis in single gene disorders or complex genetic diseases.
ADVANTAGES:
1)The DNA chip of Microarray technology shares the problem of standardization.with other molecular diagnostic techniques.
2)Accuracy of diagnosis is 85% -90%
3)Less time required for diagnosis as compared to other molecular diagnostic techniques.
4)Identification of genes and hence the associated proteins that are part of the disease process. Researchers could then use that information to synthesize drugs that interact with these proteins, thus reducing the disease's effect on the body.
5)Use of this chip may improve treatment results, cut down on side effects and reduce costs potentially spent on a priori useless drugs.
6)An array is a technology that provides massively parallel molecular-genetic information, usually in a visual format.
7)Recent studies demonstrate that chromosomal rearrangements resulting in the loss of genes that play an important role in preventing cells from becoming malignant, a phenomenon known as loss of heterozygosity can be efficiently detected with MicroArrays.
8)Open Access to a View of Systems Biology – All GeneChip microarray content is designed from genomic information in the public domain. The research community
has the opportunity to openly collaborate and share data obtained on a single standardized platform.
Arrays currently under development show promise of extending these capabilities even further.
DISADVANTEGES:
1). But if assumptions are incorrect then it will find spurious patterns and the process could go on for years never knowing that you're going in the wrong direction.
2). A kit containing a simple array with limited density can cost as little as $1,100.
3). Since the minute size of microarray features limits the amount of material that can be located at any feature, detection methods must be extremely sensitive.
CASE STUDY:
Researchers described a new class of leukemia based on GeneChip expression profiles. Using to monitor the expression of approximately 12,000 genes in 37 leukemia samples, Armstrong and his colleagues found that leukemias carrying a chromosomal translocation known as MLL have a highly distinctive pattern of gene expression that correlates with their poor prognosis. The study provides insight into the cellular origins of the disease and gene target candidates, such as the tyrosine kinase receptor FLT3, for the development of new therapies.
CONCLUSION:
State-of-the-art microarrays, optimized assays, precision instrumentation, and open access to biological information together comprise an integrated solution, which delivers the most accurate and reproducible results possible today. Reliable data means you can make better decisions, and better decisions enable you to move your research forward with confidence.
DNA microarrays are used for Global understanding of abnormal gene expression contributing to malignancy, discovery of new prognostic or predictive indicators and biomarkers of therapeutic response, prediction of drug side effects during preclinical development and toxicology studies, which predicts treatment success or failure. Targeting of therapy may improve treatment results, cut down on side effects and reduce costs potentially spent on a priori useless drugs.
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