Introduction of bioinformatics
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- 2. Introduction • Bioinformatics is the science concerned with the development and application of computer hardware and software to the acquisition, storge,analysis, and visualization of biological information. • It has the following three component. - The development of new algorithms and statistics for assessing the relationship among large sets of biological data. e.g DNA Sequence data. - Application of these tools for the analysis and interpretation of the various biological data. e.g nucleotide sequences, amino acid sequences. - The development of database of database for an efficient storage, access and management of various biological informations. • The ‘bioinformatics’ is a combination of ‘biology’ and informatics. NEETHUASOKAN
- 3. Definition • Bioinformatics derives knowledge from computer analysis of biological data. • These can consist of the information stored in the genetic code, but also experimental results from various sources, patient statistics, and scientific literature. • Research in bioinformatics includes method development for storage, retrieval, and analysis of the data. • Bioinformatics is a rapidly developing branch of biology and is highly interdisciplinary, using techniques and concepts from informatics, statistics, mathematics, chemistry, biochemistry, and physics. • It has many practical applications in different areas of biology and medicine. NEETHUASOKAN
- 4. History of bioinformatics • The collection of amino acids sequences was complied in the ‘ Atlas of protein sequence and structure’ by the National Biomedical Foundation. • This collection was edited by margaret O.Dayhoff from 1965 to 1978. • Dayhoff and coworkers contributions to the comparison of amino acid sequences by developing computer software for detecting distantly related sequences. • The EMBL established their data library in 1980 to collect, organize and distribute nucleotide sequence data and related information. • NCBI was established in U.S.A. NCBI serves as primary information databank and provider of information. • The National Biomedical Research Foundation established the PIR in 1984. NEETHUASOKAN
- 5. DNASequences • The symbols used to represent DNA sequence data. • The four bases are denoted by single letters A (Adenine), C (cytosine ), G (guanine), and T (Thymine) • But often sequence data contain ambiguities in that it is not clear as to which of the four base present at several positions. • For example , the sequence data may indicate that the base present at a specific position may be either G or A, it is purine. • Similarly , if a position may have either C or T, it is pyrimidine. • The base sequence of the two complementary strands of a DNA molecules are represented by this system of symbols. NEETHUASOKAN
- 6. AminoAcid Sequences of Proteins • The amino acids were conventionally represented by three- letters symbols..e.g. Ala for alanine, Val for valine, etc. • But in Bioinformatics, they are denoted by single letter, e.g A for alanine C for cyctine, D for aspartics acid, etc. • But some position in protein sequences have ambiguities this situation is comparable to that for DNA sequences. • For e.g , it may not be clear that a position has glutamine or glutamic acid , the position is given the symbol Z. • The Protein synthesis begin at the N-terminus and proceeds to the C-terminus. • The amino acid Sequences in databases are listed from the N- terminus to the C-terminus of the polypeptide. NEETHUASOKAN
- 7. Conti... Single letter code Amino acid Three letter Code A Alanine Ala B Asparagine Asx C Cystine Cys D Aspartic acid Asp E Glutamic Acid Glu F Phenylanine Phe G Glcine Gly H Histidine His I Isoleucine Ile K Lysine Lys L Leucine Leu M Methionine Met NEETHUASOKAN
- 8. Conti..... Single letter code Amino acid Three letter Code N Asparagine Asn P Proline Pro Q Glutamine Glu R Arginine Arg S Serine Ser T Threonine Thr V Valine Val W Tryptophan Trp Y Tyrosine Tyr Z Glutamic acid Glx X Any amino acid Xaa NEETHUASOKAN
- 9. Types of Sequences in Nucleotide Sequence Databases • The databases on DNA sequences contain a different types. cDNA sequences : • A cDNA molecule is obtained by reverse transcription of an RNA molecule. • The cDNA sequences, therefore represent that part of the genome that is transcribed into RNA. • If the cDNA is obtained from mRNA, it will represent only the exon sequences of the gene expressed in the concerned cell / tissue/organisms. Genomic DNA sequences : • These sequences represent the complete genome of the organisms. • When the genome sequences is completed, it will contain the sequences of the entire genome of the organisms. NEETHUASOKAN
- 10. Cont... • In Case of prokaryotes, genome consists of usually, a single chromosome, while in case of eukaryotes it relates to the nuclear DNA Expressed Sequence Tag (EST) sequences : • The sequences are obtained by sequencing only a part of the cDNA molecules produced using mRNA. • These sequences are dubbed as ‘tags’ because they can be used as probes for the isolation of the concerned genes from the genomic DNA. • This approach was used by J. Craig Venter and his group for obtaining the sequence of expressed portion of human genome. • The EST technique generated enormous sequence data that permitted the construction of a preliminary transcript map of the human genome. NEETHUASOKAN
- 11. Conti... Genome Sequence Tag (GST) Sequences: • GSTs were developed for identifying the genes of Plasmodium falciparum. • It was observed that the enzyme mung bean nuclease (Mnase) cuts P.falciparum genomic DNA between genes. • GSTs are developed by sequencing the DNA Fragments on either side of the points of cuts generated by Mnase. Organellar DNA Sequences: • Organellar DNA is the DNA found in mitochondria (mtDNA ) and chloroplasts (cpDNA). • The sequence of the data are complied in databases. NEETHUASOKAN
- 12. Branches of Bioinformatics • A living cell is a system where cellular components such as genome, the gene transcript, and the proteins interact with each other, and these interactions determine the fact of the cell. e.g Whether a stem cell is going to become a liver cell or a cancer cell. The three branches of bioinformatcs... 1. Genomics 2. Transcriptomics 3. Poteomics NEETHUASOKAN
- 13. Conti.... Genomics Makes Trancriptomics Makes Proteomics The three major branches of Bioinformatics DNA RNA Protein NEETHUASOKAN
- 14. Genomics : • Genomics play a significant role in modern biological research in which the nucleotide sequences of ali the chromosomes of an organism are mapped and the location of different genes and their sequence are determined. • This involves extensive analysis of the nucleic acids through molecular biology techniques before the data are ready for processing by Computer. • It is a science that attempts to describe a living organisms in terms of the sequence of its genome. • It Was not reliable to estimate the number of genes in an organism based on the number of nucleotide base pairs because of the presence of high numbers of redundant copies of many genes. • Genomics has helped to rectify this problem. NEETHUASOKAN
- 15. Conti... • Genomics uses technique of molecular biology and bioinformatics to identify cellular components such as proteins, rRNA, tRAN,etc and analyse the sequences attributed to the structural genes regulatory sequences, and non-coding sequence. • The first automatic DNA sequencer was developed in 1986 by Leroy Hood. • Haemophilus influenzae was the first bacterium to be sequenced in 1995. • Even if one can identify all the genes on a genome , the genes only indicate that, at some point in time, it might be transcribed to produce cellular componts. • eg. A human genome contains about 30,000 to 60,000 protein coding genes, but only a subset of them is expressed in a particular cell type at a particular time. NEETHUASOKAN
- 16. Transcriptomics • Transcriptomics is the study of the transcriptome, which includes the whole set of mRAN molecules in one or a population of biological cells. • This study helps us to depict the expression level of genes, often using techaniques such as DNA microarrys, that is capable of sampling ten thousands of different mRNAs at a time. • This kind of new technique has helped biologist to routinely monitor the gene expression between the control cells and treatment cells. • Transcriptomics has a few limitations • The relative abundance of transcripts as characterized by the sequential analysis of gene expression (SAGE) or microarry experiments. NEETHUASOKAN
- 17. Conti.... 1. Differential adaptation to the translational machinery. 2. Differential usage of amino acid of different abundances. 3. The lack of information on post-translation modification of amino acid residues although post-transcriptional modification such as acetylation , hydroxylation, glycosylation, phosphorylation, and cleavage are fundamental in understanding the interaction of cellular components. Proteomics : • Proteomics represents the earliest to identify a major sub- class of cellular components, the proteins and their interactions. • Proteomics involves the sequencing of amino acid in a protein determining its 3D structure and relating it to the function of the protein. NEETHUASOKAN
- 18. Cont... • Before computer processing comes into the picture, extensive data, particularly through crystallography and nuclear magnetic resonance (NMR). • With such data known as proteins, the structure and its relationship to the function of newly discovered proteins. • In such areas, bioinformatics has enormous analytical and predictive potential. • Metabolic proteins such as haemoglobin and insulin have been subjected to intensive proteomic investigation. • The term ’proteomics’ was coined to make an analogy with genomics. • Scientists feel that the bioinformatics of proteins is crucial , to understands the cellular components and the interactions completely. NEETHUASOKAN
- 19. Aims of Bioinformatics • The various important ways in which bioinformatics can be used. • The aim of bioinformatics is fourfold and includes data acquisition, tool and database development, data analysis, and data integration. Data Acquisition: • Data Acquisition is primarily concerned with accessing and storing data generated directly from the biological experiments. • The data generated by various sequencing projects have to be retrieved in the appropriate format, and capable of being linked to all the information related to the DNA samples. • The data are organized in different databases so that the researchers can access existing information. NEETHUASOKAN
- 20. Tool and Database Development • Many laboratories generate large volumes of data such as DNA sequences, gene expression information, 3D molecular structure , and highly-throughput screening. • Consequently, they must develop effective databases for storing and quickly accessing data. The other aim is to develop tools and resources that aid in the analysis of data. Data Analysis: • The third aim is to use these tool to analyse the data and interpret the results in a biologically meaningful manner. Efficient analysis require an efficiently deigned database. • It must allow researchers to place their query effectively and provide them with all the information they need to begin their data analysis. NEETHUASOKAN
- 21. Conti... • If queries cannot be performed , or if the performance is too slow, the whole system breaks down since scientists will not be inclined to use the database. Data Integration : • Once information has been analysed , a researcher must often associate or integrate it with the related data from the other databases. • For e.g a scientist may run a series of gene expression analysis experiments and observe that a particular et of 100 genes is more highly expressed in a cancerous lung tissue than in a normal lung tissue. • The scientist may wonder which of the genes is most likely to be truly related to the disease. NEETHUASOKAN
- 22. Bioinformatics Applications Molecular medicine : • The human genome will have profound effects on the fields of biomedical research and clinical medicine. Every disease has a genetic component. • This may be inherited or a result of the body's response to an environmental stress which causes alterations in the genome (eg. cancers, heart disease, diabetes.) • The completion of the human genome means that we can search for the genes directly associated with different diseases and begin to 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. NEETHUASOKAN
- 23. Conti... • Personalised medicine: • Clinical medicine will become more personalised with the development of the field of pharmacogenomics. This is the study of how an individual's genetic inheritence 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 make 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. NEETHUASOKAN
- 24. Conti... 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. NEETHUASOKAN
- 25. Conti... 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. NEETHUASOKAN
- 26. Conti... • The reality of bioweapon 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 Defence as part of a biowarfare response program to prove to the world the reality of bioweapons. The researchers also hope their work will discourage officials from ever relaxing programs of immunisation. This project has been met with very mixed feelings. NEETHUASOKAN
- 27. Conti..... Antibiotic resistance : • Scientists have been examining the genome of Enterococcus faecalisa 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. NEETHUASOKAN
- 28. References • Bioinformatics Principles and Applications – Zhumur Ghosh, Bibekanand Mallick. • Bioinformatics – B.D Singh • WWW.Scfbio.iitd.org • WWW.ncbi.nim.nih.gov • http.//genes.mit.edu/Genscan html. NEETHUASOKAN