Pcmd bioinformatics-lecture i
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Molecular Medicine in Collaboration with Bioinformatics
M. Kamran Azim, Ph.D.International Center for Chemical and Biological Sciences
H.E.J. Research Institute of Chemistry, Dr. Panjwani Center for Molecular Medicine and Drug Research
University of Karachi
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What is Bioinformatics?
Bioinformatics is the science of storing, retrieving and analyzing large amounts of biological information. It cuts across many disciplines, including biology, computer science and mathematics. (as defined by EBI)
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Application of Bioinformatics in Molecular Medicine
Molecular basis of pathogenicity; e.g. Amyloid protein in neurodegenerative diseases
Novel targets of therapeutic intervention; e.g. Caspase inhibitors in diseases characterized by tissue degradation
Molecular Diagnostics; e.g. Bird Flu
Host-pathogen interaction; e.g. Bacterial adherence factors
Novel Research tools; e.g. GFP-based techniques
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How Bioinformatics can support Molecular Medicine?
Genome-level sequence analysis of medically important organisms in order to;
gain comprehensive knowledge for their life cycle,characterization of disease causing factors,identify new targets for therapeutic intervention
Development of Bioinformatics such as novel algorithms, specialized databases and java-based tools for application in genomics and proteomics.
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Catalysts for Bioinformatics
Large-scale DNA/genome sequencing projects have led to an explosion of information concerning the DNA and protein sequence data.
Development in the field of computer technology including the use of computerized databases for storing, retrieving and comparing sequences; computer graphics for displaying and manipulating three-dimensional structures.
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6http://www.ncbi.nlm.nih.gov/Genbank/genbankstats.html
The explosion in sequence information
billions of bases from over 100,000 species
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Bioinformaticsand
Molecular basis of life
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Central paradigms of Molecular Biology and
Bioinformatics
DNARNA
ProteinFunction
Genetic InformationProtein
FunctionCell
TissuesOrganismPopulation
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DNA for Information
Protein for Execution
Bioinformatics as the Science of Sequence
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Molecular Biology in Urdu poetry
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Frederick Sanger and the Science of Sequence
at MRC, Cambridge University First Nobel Prize (1958)
was awarded for developing methods to determine the order (sequence) of the building blocks of the protein, insulin.
Second Nobel Prize (1980) for developing several and ever-improving methods to sequence nucleic acids (DNA and RNA).
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Prof. Zafar H. Zaidi and Bioinformatics
Pioneered Protein Chemistry;Protein Sequencing;Sequence analysis(1975-2001)
Initiated Bioinformatics;Protein Structure Prediction,Homology modeling(1991-2001)
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Scope of topics Biological databases (utilization, development and
integration etc.) Analyses of nucleotide and protein sequence
information Analyses of 3D structural data of macromolecules. Assessment of how small molecules interact with
macromolecules in biological systems. Studies on networks of protein-protein
interactions Simulation of biological processes More
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Scope of topics Biological databases (utilization, development and
integration etc.) Analyses of nucleotide and protein sequence
information Analyses of 3D structural data of macromolecules. Assessment of how small molecules interact with
macromolecules in biological systems. Studies on networks of protein-protein
interactions Simulation of biological processes More
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Bioinformatics Resources
Sequence Databases 1960s; The first sequences to be collected were those of proteins by Margaret Dayhoff at the NBRF, Washington, USA. [Protein sequence atlas; PIR]
1970s; First DNA sequences databases were (a) the GenBank at Los Alamos National Labotaroy, New Maxico, USA (b) EMBL at the European Molecular Biology Laboratory at Heidelberg, Germany.
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Primary Bioinformatics Databases
DNA sequence databasesGenBank, EMBL and DDBJ
Genome Centers databasesSanger Center, TIGR
Protein sequence DatabasesSwissProt, PIR, UniProt
Protein 3D structure databasesPDB, SCOP, CATH
Specialized databasesMEROPS, Protein Kinase Resource
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Accessing Bioinformatics Databases
ENTREZ; a window-based program with a web-based interface developed at the NCBI, USA.
SRS; similar service at the EBI, UK.
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Specialized databases useful in Molecular Medicine
OMIM- Online Mendelian Inheritance in Man. This database is a catalog of human genes and genetic disorders.
ENSEMBL- is designed to allow free access to all the genetic information available about the Human Genome.
Human Gene Mutation DB- contains sequences and phenotypes of human disease-causing mutations.
KEGG- to computerize knowledge of molecular interactions namely metabolic pathways, regulatory pathways and molecular assemblies.
dbSNP- Single Nucleotide Polymorphisms DB GeneCards- an integrated DB of human genes that
includes automatically-mined genomic, proteomic and transcriptomic information, as well as orthologies, disease relationships, SNPs, gene expression, gene function etc.
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Scope of topics Biological databases (utilization, development and
integration etc.) Analyses of nucleotide and protein sequence
information Analyses of 3D structural data of macromolecules. Assessment of how small molecules interact with
macromolecules in biological systems. Studies on networks of protein-protein
interactions Simulation of biological processes More
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Sequence Analysis
Sequence Analysis Programs As more DNA sequences became available
in the late 1970s, interest also increased in developing computer programs to analyze the sequences.
In early 1980s, the Genetics Computer Group (GCG) was started at the University of Wisconsin, USA, offering a set of programs for sequence analysis.
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Sequence Analysis
Methods for Comparing Sequences
The Dot Matrix method (DOTPLOT, COMPARE) Dynamic programming matrices Word or k-tuple methods (FASTA, BLAST)
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Sequence analysis by DotPlotsK A M R A N
K *A * *M *R *A * *N *
KAMRANKAMRANAlignment
K A M R A N
K *EM *R *A * *N *
KAMRANKEMRAN
Substitution
K A M R A A N
K *EM *R *A * *N *
KAMRAANKEMRA-N
Insertion/deletion
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DotDlot analysis; repetitive sequencesK A M R A N K A M R A N
K * *E
M * *R * *A * * * *N * *K * *E
M * *R * *A * * * *N * *
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Dynamic Programming for sequence alignment
identity and substitution scoring, gap penalty
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Sequence Analysis
Sequence comparison and alignmentPairwise sequence alignment
FASTA; BLASTMultiple sequence alignment
PILEUP; ClustalW Pattern search; PROSITE Phylogenetic analysis; Phylip Genome-level sequence analysis
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Pairwise sequence alignment of(a) human and chicken cathepsin B and (b) human and hookworm cathepsin B.
Identical residues are indicated as dark blocks.
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Multiple sequence alignment
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Multiple sequence alignmentof the family of kunitz-type proteinase inhibitors
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Phylogenetic Analysis of kunitz-type proteinase inhibitors based on multiple sequence alignment
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Scope of topics Biological databases (utilization, development and
integration etc.) Analyses of nucleotide and protein sequence
information Analyses of 3D structural data of macromolecules.
three dimensional strutures and Structural Bioinformatics
Assessment of how small molecules interact with macromolecules in biological systems.
Studies on networks of protein-protein interactions Simulation of biological processes More
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End Note Bioinformatics is the body of Knowledge; A wealth of data on sequences and structures.
Key Resource is KNOWLEDGE
And the key technology is INFORMATION HANDLING
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Leading Bioinformatics InstitutionsEuropean Bioinformatics Institute, Cambridge, UKNational Center for Biotechnology Information, USANational Human Genome Research Institute, USAEMBL, Heidelberg, GermanyJ. Craig Ventor Institute, USA[formerly The Institute of Genome Research (TIGR)]The Sanger Institute, UK
Bioinformatics Journals and BooksBioinformaticsGenome ResearchNucleic Acid ResearchBioinformatics by D.W. MountIntroduction to Bioinformatics by AttwoodStructural Bioinformatics by P.E. BourneBioinformatics; A beginner’s Guide by ClaverieBioinformatics Computing by B. Bergeron
Bioinformatics SocietiesInternational Society for Computational Biology (ICSB)Asia Pacific Bioinformatics Network (APBioNet)European Conference on Computational Biology (ECCB)