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Draft Syllabus for the

M.Sc. Bioinformatics (With effective from: June 2010)

SWAMI RAMANAND TEERTH MARATHWADA UNIVERSITY

NANDED

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S.R.T.M.University, Nanded, M.S., India Course Structure for M.Sc. Bioinformatics

(T =Theory, P = Practical) First year

Course No. Course Name Teaching periods per week Total Marks

Semester-I Theory Practical MBI-101 (T) Basics of Biology and Biochemistry 4 50 MBI-102 (T) Genetic Information Flow & Processing 4 50 MBI-103 (T) Introduction to Bioinformatics 4 50 MBI-104 (T) Basic Concepts in Computing 4 50 MBI-105 (P) Lab Course Based on MBI-103 4+4 50 MBI-106 (P) Lab Course Based on MBI-104 4+4 50 Total= 300 Semester-II Course No. Course Name Total Marks

MBI-201 (T) Molecular Cell Biology and Genetics 4 50 MBI-202 (T) Statistical Methods in Bioinformatics 4 50 MBI-203 (T) Chemo informatics and Biodiversity Informatics 4 50 MBI-204 (T) Programming in C 4 50 MBI-205 (P) Lab Course Based on MBI-202 & MBI-203 4+4 50 MBI-206 (P) Lab Course Based on MBI-204 4+4 50 Total= 300 Total Marks (Semester I + Semester II) = 600

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Second year

Course No. Course Name Teaching periods per week Total Marks

Semester-III Theory Practical Course No. Course Name Total Marks

MBI-301 (T) Immunology and Parasite Bioinformatics 4 50 MBI-302 (T) Taxonomy & Phylogeny 4 50 MBI-303 (T) Structural biology & Molecular Modeling 4 50 MBI-304 (T) Biological Database Management 4 50 MBI-305 (P) Lab Course Based on MBI-302 & MBI-303 4+4 50 MBI-306 (P) Lab Course Based on MBI-304 4+4 50 Total= 300 Semester-IV

Course No. Course Name Total Marks

MBI-401 (T) Metabolomes and Metabolic Pathway Engineering 4 50

MBI-402 (T) Programming in Perl 4 50 MBI-403 (T) Comparative Genomics and Proteomics 4 50 MBI-404 (T) Genome to Drug and Vaccine 4 50 MBI-405 (P) Lab Course Based on MBI-402 & MBI-403 4+4 50 MBI-406 (P) Seminars and Project Work 4+4 50 Total= 300 Total Marks (Semester III+ Semester IV) = 600 Total marks (First year + Second year) =1200

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(MBI-101) Basics of Biology and Biochemistry

I Basic Biology

Objectives: The course aims at exposing the students to the diversity of microbial, plant and animal life. At the conclusion of the course the student would have become familiar with outlines of the classification of the organisms, their structural organization and functional complexities. 1. Bacteria and Viruses

Bacteria: Structure of bacterial cell; bacterial types; transformation, transfection, transduction and conjugation; nutrition; phylogeny

Viruses: Biology of viruses; bacteriophages, plant and animal viruses; replication of viral genome; HIV 2. Protists and Fungal World Protists: protozoans, algae, slime and water molds Fungal World: Feeding, reproduction, diversity and relationships 3. Plants and Animals Plant Diversity: Broad classification and inter-relationships of non-vascular and vascular plants; tissue organization; reproductive patterns; transport mechanisms, growth, photosynthesis, hormones. Animal Life: Major animal phyla, characteristics and interrelationships; tissues, organs and organ systems; principles of nutrition, digestion, thermoregulation, Osmoregulation and excretion, muscle contraction, neural reflexes, circulation, respiration and endocrines.

II Biochemistry

Objectives: The objective of the course is to make the students understand the chemistry of different classes of biomolecules, their interactions in an aqueous environment, the structure-function relationships of macromolecules. The principles of enzyme catalysis and regulation, organization of metabolic systems 4. Chemistry of Biomolecules Water as the universal biological solvent; concept of osmolarity. Carbohydrates: monosaccharides, oligosaccharides, polysaccharides, proteoglycans and glycoproteins. Lipids: fatty acids, acylglycerols; phospholipids, sphingolipids, cholesterol and membranes Isoprenoids, icosanoids and their biological importance. Proteins: amino acids and peptides; primary, secondary, tertiary and quaternary structures; structure, function and evolutionary relationships;

protein – protein interactions protein folding; allosteric proteins. Nucleic acids: bases, nucleotides, RNA and DNA; different structural forms of DNA; denaturation, renaturation and hybridization of DNA;

different types of RNA; Protein-nucleic acid interaction. Enzymes: details of enzyme nomenclature and classification; units of enzyme activity; coenzymes and metal cofactors; temperature and pH effects;

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Michaelis-Menten kinetics; Inhibitors and activators; active site and catalytic mechanisms; covalent and non-covalent regulations;

isoenzymes; osmolytes and intracellular modulation of enzymes. 5. Organization of metabolic systems Enzyme chains, multi-enzyme complexes and multifunctional enzymes; anaplerotic sequences and amphibolic pathways; pacemaker enzymes and feedback control of metabolic pathways; shuttle pathways; energy charge. Oxidation of glucose in cells: high energy bond, glycolysis, citric acid cycle and oxidative phosphorylation. Reference Books:

1. Biogenesis: Theories of life's origin by Lahav, N., New York. Oxford University Press, 1999.

2. Big-time biology by Beardsley Tim, Scientific American, 1994. 3. The Science of Life by R. A. Wallace, G. P. Sanders & R. J. Ferl, Harper Collins

Publishers, Biology, 1991. 4. Fundamentals of Biochemistry (2

nd edition) by D., Voet, Voet, J.G. & Pratt, C. W.

John Wiley & Sons, 2006. 5. Principles of Biochemistry (4

th edition) by Horton, H. R., Moran, L.A.,

Scrimgeour, K.G., Perry, M. D. & Rawn, J. D., Pearson-Prentice Hall,2006. 6. Lehninger, Principles of Biochemistry (4

th edition) by Nelson, D. L. & M. M.

Cox, W. H. Freeman & Co., 2005.

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(MBI-102) Genetic Information Flow & Processing

Objectives: The aim is to make the student understand the current concepts in gene organization, transcription, translation and regulation of gene function as well as the biotechnological implications of recent developments in cloning and genome sequencing. 1 Introduction

Introduction: DNA as a genetic material. – Experiments done to prove this. Nucleic acid structure: Single stranded, double stranded. Secondary structures in single stranded molecules. Alternative double helical structures in double stranded DNA; Closed DNA as Super coiled molecule. 2. Genome Organization and Evolution Prokaryotic and eukaryotic genomes: C value paradox. Repetitive and non-repetitive DNA, transposons and retroposons. Exons and introns – organization of interrupted genes, one DNA sequence may code for multiple proteins. Gene numbers – essential genes and total gene number, gene clusters, Pseudogenes. Gene families – globin gene and immunoglobulin gene families; Organelle genome – mitochondrial and chloroplast. Packaging of genome – Bacterial genome as nucleoid. Eukatryotic genome – nucleosomes, chromatin, solenoids, loops, domains, scaffolds, chromosomes.

Evolution of Genomes. 3. DNA replication Prokaryotic DNA replication – DNA polymerases, origin of replication, initiation, elongation and termination of replication, Rolling circle model of replication. Eukaryotic DNA polymerases – multiple origins of replication, process of replication; Regulation of replication in both prokaryotes and eukaryotes. 4. DNA damage, repair and recombination Different types of DNA damages. Variety of DNA repair systems in prokaryotes and eukaryotes – Base excision repair system. Nucleotide excision repair system, Mismatch repair system, Recombination repair system; Recombination – homologous and non- homologous recombination. 5. Gene Expression – Transcription and Translation: Transcription in prokaryotes – RNA polymerase, initiation, elongation and termination of transcription. Regulation of transcription – operon concept, lactose and Tryptopahn operons. Transcription in eukaryotes: Different RNA polymerases – requirement of promoters by these RNA polymerases, Initiation, elongation and termination

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by these polymerases;. Processing of transcripts – 5’ capping, 3’ polyadenylation, splicing and editing; Regulation of transcription – Response elements, enhancers and silencers, HLH, Leucine zipper proteins., noncoding RNAs. Translation in prokaryotes: protein synthesis machinery – mRNA, tRNA and rRNA molecules; initiation, elongation and termination of translation; Genetic code – interpreting genetic code; Accuracy of translation. Eukaryotic translation: protein synthesis – initiation, elongation and termination; Post-transnational modifications of proteins; protein degradation; Regulation of translation - mRNA stability, 5’ and 3’ UTRs, mRNA Localization. Gene regulation by post-translational modifications of proteins (acetylation, methylation, ribosylation, phosphorylation etc.) and different intermediate RNAs (ribozymes, miRNAs, siRNAs etc.) Reference Books:

1. Genes VIII by B. Lewin, Pearson-Prentice Hall, 2004. 2. Essentials of molecular biology by D. Freifelder, New Delhi, Narosa Publishing

House, 2001. 3. Genetics from Genes to Genomes by L. H. Hartwell, L. Hood, M. L. Goldberg,

A.E. Reynolds, L. M. Silver & R. C. Veres, McGraw-Hill, 2004. 4. Human Molecular Biology by R. J. Epstein, Cambridge University Press, 2003. 5. Molecular Biology by D. Clark, Elsevier publishers, 2005 6. Genetics: A Molecular Approach (2

nd edition) by P.J. Russell, 2006.

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(MBI-103) Introduction to Bioinformatics

Objectives: • Understand the nature of biological data and need for Biological databases • Understand and explore the major biomolecular sequence databases (organization and contents)

and their respective search engines and database searches • Understand and appreciate the need and significance of sequence analysis and the

bioinformatics approaches for the same • Application of software analysis tools to sequence data 1 Introduction

Various Definitions History of Bioinformatics Bioinformatics in business. Scope of Bioinformatics. Bioinformatics Applications

Nature of biological data 2. Introduction to Biological databases What is Database?

Types of Databases Biological databases: Primary databases – GenBank, DDBJ, EMBL.

Protein sequence databases – Uniprot-KB: SWISS-PROT, TrEMBL, UniParc. PIR-PSD, PRINTS. Structural databases – PDB, NDB, PubChem, ChemBank, CCSD. Derived Darabases: Sequence- InterPro, Prosite, Pfam, ProDom. Structure- FSSP, DSSP. Specialized – FlyBase, HIV, BLOCKS, EST, SNP, AceDB, Microarray. Genome & genetic disorders – Genome databases at NCBI, EBI, TIGR, SANGER Human, model organisms, Microbes & Viral; OMIM. 3. Data Retrieval and Information Search Google, Bibliographic resources related to Life Sciences viz., PubMed, BioMed Central, Public Library of Sciences(PloS), citeXplore.Database search engines – Entrez, SRS etc. Biological Data warehousing and Data mining concept. Database Similarity Searching – FASTA, BLAST. Searches on Medline, etc. 4. Data generating Techniques Genome sequencing, PCR, RFLP, Fingerprinting, RAPDs, Microarrays, ESTs, X-ray Crystallography, NMR. 5. Problem Solving in Bioinformatics

Concepts in sequence analysis – Overview. Various file formats for bio-molecular sequences: GenBank, FASTA, GCG, MSF. Scoring matrices for Nucleic acids and proteins – PAM, MDM, BLOSUM, CSW. Pairwise sequence alignment algorithms – Needleman & Wunsch, Smith &

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Waterman. Multiple sequence alignment – CLUSTALW, PRAS. Human Genome Project. Genetic Diversity – Single Nucleotide Polymorphism (SNP) Gene Prediction. Reference Books:

1. Bioinformatics: Sequence and Genome Analysis by David Mount, New York, Cold Spring Harbor Laboratory Press, 2004.

2. Introduction to Bioinformatics by Attwood, T.K. & Parry-Smith, D.J., Delhi, Pearson Education (Singapore) Pte.Ltd., 2001.

3. Bioinformatics: A Practical Guide to the analysis of Genes and Proteins (2nd

Ed.) by Baxevanis, A.D. & Ouellettee, B., F. F., New York, John Wiley & Sons, Inc. Publications, 2002.

4. Bioinformatics: Concepts Skills and Applications by S. C. Rastogi, Namita Mendirata, Parag Rastogi, Estern Economi Edition, PHI (Prentice – Hall India), 2006.

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(MBI-104) Basic Concepts in Computing

Objectives: To introduce the students to fundamentals of computers, computing and software. 1. Introduction Overview and functions of a computer system, storage, devices, memory, etc Types of Processing: Batch, Real-Time, Online, Offline Types of modern computers: The workstation, The Minicomputer, Mainframe Computers, Parallel Processing Computer, The Super Computer, etc The Internet and its Resources, World Wide Web (WWW): associated tools, services, resources and various terminologies Introduction to operating systems: DOS/Windows/Unix/Linux File System Concept – NTFS, FAT etc. 2. Computer Networking; Network and Data security OSI Reference Model, TCP/IP, topologies and protocols, designing networks Networking gadgets (Router, Switch, etc); Data Communication (ISDN, VPN, DSL, cable modem, cellular modem, etc); Communication Links (Wire pairs, Coaxial cables, Fiber optics, Microwave, Satellite, etc) Network security fundamentals: types of attacks, firewall, packet filtering, classification of data security threats, protection mechanism (authentication, access control, access rules) An overview of Computer viruses: How do they get transmitted? What are the dangers? General Precautions to be taken. Encryption/Decryptions techniques Current & future technologies (Grid Computing, VPN, wireless, mobile computing, biometrics etc.) 3. Introduction to Windows Operating System Features of MS Windows – GUI, Multitasking etc. Elements of Windows – Desktop, Windows, Applications, Icons, Group window etc. Main modules of Windows O.S. – Program Manager, File manager, Control Panel, Networks, Print manager. Switching between applications – Running MS DOS applications, Windows Help. Study of Windows important files – DLL, INI, etc. 4. Introduction to Linux Operating System Introduction to Linux – Features of Linux; Hardware Requirements Installation.

Linux Commands and Utilities – Add User, alias, at, banner, batch, bind, cat, cd, chmod, chown, chroot, cp, cpio, dc, dd, df, dir, du,dump, grep, zip, unzip, gzip, halt, hostname, kill, locate, lpc, lpd, lpr, lprm, ls,mail, man, mcopy, mdel, mdir, mformat, mkdir, mlevel, more, mount, mt, mv, passwd, ping, , ps, pwd, rm , rmdir, set, shutdown, sort, stat, su,tar,tree, umount, unzip, vdir, vi, view, wc, who, whoami, zip,

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Reference Books:

1. Computers Today by Sanders D. H., McGraw Hill. 2. Fundamentals of Computers by Rajaraman V., PHI. 3. Introduction to Computers by A. Leon and M. Leon, Vikas Publishing House. 4. Computer Architecture and Organizations by J. P. Hayes, Mc Graw Hill. 5. Computer Network by Andrew S. Tanenbaum, PHI. 6. Inter Networking With TCP/IP: Principles, Protocol And Architecture by

D.E. CornerVol1, 2nd Edition Prentice Hall, 1991. 7. Linux. The Complete Reference.

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(MBI-201) Molecular Cell Biology and Genetics

Objectives: The objective is to expose the student to the principles of structure and function of cells, membranes and organelles, laws of inheritance and population genetics. 1 Life Begins with Cell Molecules of Cell Cells and Genomes Cell Chemistry and Biosynthesis An overview of organelles, (mitochondria, chloroplasts, ER, Golgi, lysosomes and peroxisomes; nucleus and nucleolus) and organelle genetic systems. Working of Cell 2. Internal Organization of Cell Prokaryotic and eukaryotic cell membranes and cellular compartmentation. Cellular membranes: Structure, transport, channels, carriers, receptors, endocytosis, membrane potentials. Cell motility and shape: cytoskeletal elements, cilia and flagella; motor proteins. Cell-cell interactions and signal transduction: Intercellular junctions, signaling by hormones and neurotransmitters; receptors, G-proteins, protein kinases and second messengers Protein traffic in cells: Protein sorting and signal sequences; protein translocation in ER and vesicular transport to Golgi, lysosmes and plasma membrane; protein import into nuclei, mitochondria, chloroplasts and peroxisomes. Cell cycle and its regulation; events during mitosis and meiosis; Mechanics of cell division; Programmed cell death. 3. Intigrating Cells into Tissues Cell-Cell and cell matrix adhesion: an overview The extracellular matrix of epithelial sheets The extracellular matrix of non-epithelial tissues Plant Tissues 4. Molecular Basis of Development Different types of DNA damages. Variety of DNA repair systems in prokaryotes and eukaryotes – Base excision repair system. Nucleotide excision repair system, Mismatch repair system, Recombination repair system; Recombination – homologous and non- homologous recombination. 5. Development of Multicellular Organisms Universal mechanism of animal development Cell movements and shaping of the vertibate body 5.3 Plant development 6. Cancer Genetic basis of Cancer Mutations causing loss of growth inhibiting and cell cycle controls

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The role of carcinogens and DNA repair in cancer 7. Genetics Science of genetics – objectives, terminologies, methods Mendelian principles of inheritance, sex linked inheritance Chromosomes, linkage, linkage maps and recombination Mutations – molecular, gene/point and chromosomal Gnetics of viruses and bacteria Phenotype and genotype relationships, role of environment, from gene to phenotype, gene interactions Study of quantitative traits Genetics of populations, genetics and evolution Reference Books:

1. Essential Cell Biology (2nd

edition), by B. Alberts, D. Bary, K. Hopkin, A. Johnson, J. Lewis, M. Raff, K. Roberts & P. Walter, Garland Science, 2004.

2. The Cell: A Molecular Approach by G. M. Cooper, A. S. M. Press, 2000. 3. Molecular Cell Biology (5

th edition) by H. Lodish, A. Berk, P. Matsudaira,

C.A. Kaiser, M. Krieger, M. P. Scott, S. L. Zipursky & J. Darnell, W. H. Freeman & Company, 2004.

4. Principles of Genetics (8th

edition) by E. J. Gardner, M. J. Simmons & D. P. Snustad John Wiley & Sons, 2002.

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(MBI-202) Statistical Methods in Bioinformatics

Objectives: To upgrade the skills of the students in statistics those are essential for learning Bioinformatics 1 Introduction

Definition Concept of statistical population Concept of statistical sample Concept of Data – Discrete and continuous data Representation of data – Histogram, PolyGram, Frequency curve, Pie Diagram

2. Elementary Statistics Arithmetic Mean – Definition for ungrouped and grouped data. Combine mean, weighted mean.

Median – Definition, formula, and computation for ungrouped and grouped data.

Mode – Definition, formula, and computation for ungrouped and grouped data.

Quartiles – Definition, formula, and computation for ungrouped and grouped data. Range – Definition for ungrouped and grouped data.

3. Probability Theory Experimental Probability & Probability law. Probability functions – Probability mass function, Probability density function

Random Variables – Discrete & Continuous Random Variables, Definitions The Mean of a Discrete Random Variable The Mean, Variance, and Median of a Continuous Random Variable Definitions Chebyshev’s Inequality The Variance of a Discrete Random Variable General Moments of a Probability Distribution The Probability-Generating Function Continuous Random Variables Probability Distributions and Parameters Independence Probability Distributions – Discrete and Continuous Discrete Probability Distributions – One Bernoulli trial, The Binomial, Distribution, The Hyper geometric Distribution, The Uniform Distribution, The Geometric Distribution, The Poisson distribution, Approximations

Continuous Distributions – The Uniform Distribution, the Normal, Distribution, the Exponential Distribution, the Gamma Distribution,

The Beta Distribution 4. Events

What Are Events? Complements, Unions, and Intersections

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Probabilities of Events Conditional Probabilities Independence of Events

5. Entropy and Related Concepts Information theory Entropy Relative Entropy Scores and Support Inference Reference Books:

1. Statistics: concepts and applications by Frank, Harry & Althoen, S. C., Cambridge University Press, 1995.

2. Introduction to probability and statistics by Lipschutz, S. & Schiller, J. J., New York. McGraw-Hill, 1999.

3. Statistical methods in bioinformatics: an introduction by Ewens, W. J. & Grant, G. R., New York. Springer, 2001.

4. Handbook of computational statistics: concepts and methods by Gentle, J.E., Hardle, W. & Mori, Y., Berlin, Springer-Verlag, 2004.

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(MBI-203) Chemoinformatics and Biodiversity Informatics

Objectives: • To provide an introduction to the major aspects of chemoinformatics, with particular emphasis

on applications in modern drug discovery. • The major aspects of Biodiversity informatics like databases of biodiversity. 1. Introduction Role of Chemoinformatics in pharmaceutical/chemical research – Integrated databases; HTS analysis; Ligand based design of compounds;

Structure based design of compounds Structure representation systems, 2D and 3D structures Chemical Databases – Design, Storage and Retrieval methods Introduction to database filters, property based & (drug-like)-Lipinski Rule of Five 2. Characterization of chemicals Introduction to pharmocophore Identification of pharmacophore features Building pharmacophore hypothesis Searching databases using pharmocophores Chemoinformatics tools for drug discovery 3. QSAR & application to Hit to lead optimization Introduction to QSAR Methods- Hansch analysis, Free-wilson QSAR, GFA Practical Session: QSAR using some public domain tools In silico ADMET; QSAR approach, Knowledge-based approach Design & Analysis of combinatorial libraries 4. Biological Diversity Biological Information Biodiversity of life – Species diversity: taxonomic information plants, animals, microbes and viruses; Genetic diversity; Ecological/ecosystem diversity; urban biodiversity Methodes for species identification classification 5. Biodiversity Databases Organizing biological species information Accessing existing databases on World Wide Web – Species 2000; Tree of Life Project; GBIF; ATCC; NBII; ICTV; AVIS; Species analyst Collaboration 6. Species Identification Software for species identification Probabilistic and deterministic identification Delta, Micro IS, AVIS, ICTV Biocomplexity issues in Biodiversity Reference Books:

1. An introduction to Chemoinformatics by Andrew R. Leach and Valerie J. Gillet, Kluwer Academic Publisher, 2003.

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2. Chemoinformatics by Johann Gasteiger and Thomas Engel, 2004. 3. Handbook of Chemoinformatics. From Data to Knowledge by Johann

Gasteiger. 4. Chemometrics and Chemoinformatics by Barry K. Lavine, ACS Symposium

series 894. 1.

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(MBI-204) Programming in C

Objectives: To be able to conceptualize and formulate the logic and flow for the implementation of a computational task and to code the same using the structured programming approach as provided by the ‘C’ programming language. 1. Introduction Types Of Programming Languages , Introduction To C ,Historical Development Of C Language, Structure Of C Program. 2. C Fundamentals The C Character Set ,Identifiers And Keywords ,Data Types, Constants , Operators Used In C ,Variables And Types Of C Variables , Declaration, Expressions ,Statements ,Symbolic Constants ,I/O Statements used in C 3. Control Statements Introduction Branching:The If Statements, If-Else Statements, If-Else ,Ladder,Switch Statements Looping :While Loop, Do-While Loop, For Loop, Multiple , Initialization In The For Loop, Nested Control Structures, Jumps In Loop, Break Statement, Continue Statements, Goto Statement 4. Arrays What Is An Array ? , Declaring And Initializing An Array , One-Dimensional Array , Multi-Dimensional Array , Passing array to function , Strings. 5. Storage Classes Automatic Storage Class , Register Storage Class , Static Storage Class External Storage Class . 6. User Defined Functions Introduction , Need For User-Defined Functions , Return Types , Passing Arguments To A Functions , Scope And Life Time Of Variables In Function, Nesting Of Functions ,Recursion ,Functions And Array. 7. Character String What Are Strings ,Declaring And Initializing String Variables ,Reading And Writing Of String ,Standard Library String Function 8. Pointers Introduction To Pointers , Declaring And Initializing Pointers , Accessing A Variable Through Its Pointer , Pointer Expression , Pointers And Arrays, Pointers And Character Strings , Array of Pointer and pointer to pointer 9. Structurs And Union Introduction ,Structure ,Structure Initialization , Array Of Structures , Arrays Within Structure ,Structure Within Structure ,Introduction To Union 10. File Manegement In C Introduction ,Defining And Opening A File ,Closing A File ,Input/Output Operations On File ,Error Handling During I/O Operations ,Random Access To

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File. 11. Introduction to OOPS Object oriented programming, Basic concepts of OOPS, Benefits of OOPS. Reference Books:

1. Programming With C By Byron Gottfried Second Edition, Tata Mcgraw Hill

2. Let Us C By Yashwant Kanetkar 4th Edition Bpb Publication. 3. Pointers In C By Yashwant Kanetkar 3rd Edition. 4. Programming in Ansi C by E. Balagurusami

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(MBI-301) Immunology and Parasite Bioinformatics

Objectives: • To provide the system-level understanding of the immune system. • To take into account the growing relevance of immunology in the design and development of

vaccines. •Understanding of life cycles and biology of select parasites as well as their interactions with the

host and vector • Understanding the role of Bioinformatics in combating parasitic diseases through parasite-

specific databases and analysis of genomic, proteomic data • Appreciating the need and approaches for novel drugs/vaccines for parasitic diseases in the

context of multidrug resistance 1. Introduction Immune systems and systems biology – Innate and adaptive immunity in vertebrates; Antigen processing and presentation Antibodies – Immunoglobulins, Immunoglobulin classes and subclasses CDR and LDR regions and sequence numbering; Immunogenetics Membrane receptors for antigen – The B-cell surface receptor for antigen (BCR), The T-cell surface receptor for antigen (TCR); Antigen recognition diversity; The major histocompatibility complex (MHC) Contemporary challenges to the immune system – Infectious diseases, Clustering of infectious disease organisms, Autoimmune diseases 2. Epitopes and primary interaction with antigen Epitopes – Affinity Maturation, Recognition of Antigen by B cells, Neutralizing Antibody, Prediction of epitopes The primary interaction with antigen – The nature of B-cell epitopes, Antigen and Antibody interaction, The specificity of antigen recognition, Binding of the peptides on the MHC, Super antigens, Tools and servers available 3. Vaccine design Categories of vaccines Polytope vaccines Therapeutic vaccines Evolution and escape due to variations Immunogenomics and viral bioinformatics 4. Parasitic Diseases to be covered Malaria Leishmaniasis Trypanosoma Entamoeba histolytica Toxoplasma Filariasis 5. Parasites and Vectors of parasites Biology of Parasites – Life Cycle, Infectivity, Demographic distribution of strains

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Parasite Genome and Proteome Databases Vectors of parasites – Biology of vectors; Genome & Proteome databases: Mosquito 6. Application of Bioinformatics Data Mining tools for Identification of Parasite-specific genes/gene products (e.g. house-keeping genes, genes essential for survival), Resistant Genes Structural genomics of parasites Host-Parasite and Host-Vector-Parasite Interactions –

Pathway databases 7. Multi-Drug Resistance Mechanism of MDR: genomic, molecular, cellular Identification of genes responsible for MDR Approaches to novel drug discovery Challenges and opportunities in vaccine development Plant Parasites and diseases – Disease resistance genes of plants;

Plant-pathogen interactions Reference Books:

1. Essential immunology. Blackwell Science by Ivan M. Roitt and Peter J. Delves, ISBN 0-632-5902-8.

2. Immunoinformatics: Bioinformatics Strategies for Better Understanding of Immune Function, ISBN 0-470-09075-8

3. Immunological Bioinformatics by Ole Lund, Morten Nielsen, Claus Lundegaard, Can Kesmir, and Soren Brnak, The MIT press, ISBN 0-262-12280-4.

4. A modern textbook of Parasitology by Latey, A.N, Pune, Narendra prakashan, 1991.

5. Modern parasite biology: cellular immunological and molecular aspects by Wyler, D.J. Ed., 1990.

6. Parasitism by Bush, A. O., Fernandez, J. C., Esch, G.W. & Seed, R. J., Cambridge. Cambridge University Press, 2001.

7. Parasite genomics protocols by Melville, S.E., New Jersey. Humana Press, 2004.

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(MBI-302) Taxonomy & Phylogeny

Objectives: • Understand the concepts in Systematics, Classical Taxonomy and Phylogeny in the viral,

microbial, animal and plant universe: basis for classification, nature of characteristic properties used for the same

• Understand the concepts of molecular evolution and the nature of data for deriving molecular phylogeny

• Understand the statistical approaches and models that can be used for Phylogenetic analysis and tree reconstruction

• Understand the computational approaches for Phylogenetic analysis and their applications 1. Introduction Systematics, Taxonomy and Phylogeny: Basic concepts – Species concept; kingdom to species; the five kingdoms; classical, phenetic and cladistic approaches; taxonomic information on viruses, microbes, plants & animals; Concepts in Molecular Evolution Nature of data used in Taxonomy and Phylogeny – Morphological and molecular character data 2. Phylogenetic trees and their comparison Definition and description Various types of trees Consensus (strict, semi-strict, Adams, majority rule, Nelson). Data partitioning and combination. Tree to tree distances, similarity 3. Phylogenetic analysis algorithms Maximum Parsimony Distance-based – UPGMA, Transformed Distance, Neighbors-Relation, Neighbor-Joining Probabilistic models and associated algorithms – Probabilistic models of evolution; Maximum likelihood algorithm 4. Approaches for tree reconstruction Character optimization Delayed and accelerated transformation. Reliability of trees. Bootstrap Jackknife Decay Randomization tests. 5. Applications of phylogeny analyses Comparison of Phylogenetic Trees obtained using DNA seq. Vs. protein seq. Vs. Full genomes. Need for addition of other properties towards total phylogenetic analysis Comparative methods for detection of species / organism relationships Gene duplication, Horizontal transfer, Domain evolution Study of co-evolution: Plant-insect interactions. Host-parasite interactions.

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Viral evolution. Reference Books:

1. Molecular Evolution a Phylogenetic Approach by R. D. M. Page and E.C. Holmes, Blackwell Scientific, 1998.

2. Fundamentals of Molecular Evolution by D. Graur and W-H Li, 2nd Edition, Sinauer Associates.

3. Protein Evolution by L. Patthy, Blackwell Scientific, 1999. 4. Practical taxonomic computing by Pankhurst, R.J., 1991

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(MBI-303) Structural biology & Molecular Modeling

Objectives: • Understanding the levels of structure organization of macromolecules and related methods of

structure determination • Knowledge of various methods of structure prediction • Understanding the interaction between macromolecules • To know the approaches for structure analysis 1. Macromolecular Structure Protein - Primary, Secondary, Super secondary, Tertiary and Quaternary structure Nucleic acid – DNA and RNA Carbohydrates 3D Viral structures 2. Proteins Principles of protein folding and methods to study protein folding Structure of Ribosome Macromolecular interactions –

Protein – Protein Protein – Nucleic acids Protein - carbohydrates

3. Macromolecular x-ray crystallography Principles of crystallography Methods to study 3D structure Co-ordinate systems Fitting and refinement Validation Analysis of 3D structures Mass spectrometry and computational approaches in structural biology 4. Molecular modelling An Overview Introduction and challenges Molecular modelling methods – Conformational searching, Potential energy maps, Ramachandran maps, Ab-initio methods, Semi-empirical methods Empirical methods. 5. Conformational analysis Introduction and Methods – Molecular fitting Conformations: global vs. local Force fields: expressions for stretch, bond, torsion, etc. Energy Minimisation – Non-derivative and derivative methods Free energy calculations Global optimisation (simulated annealing, Tabu search, genetic algorithms) Applications of energy minimisation 6. Methods for 3D structure prediction Knowledge based & Fold recognition

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Advance techniques in Prediction of 3D Structure – Hidden Markov Model, Neural networks, Rossetta Stone, Genetic algorithms Designing of molecules like drug, inhibitors using – Structure based & ligand based docking methods Different Scoring schemes Reference Books:

2. Principles of protein X-ray Crystallography by Jan Drenth, Springer-Verlag, 1994.

3. Structural Bioinformatics - Methods of biochemical Analysis V. 44 by Philip E. Bourne (Editor), Helge Weissig (Editor) New Jersey. Wiley-Liss, 2003.

4. Introduction to Protein Structure by Branden, Carl & Tooze, John, Garland Publishing, 1991.

5. Molecular Modeling: Principles and Applications by Andrew Leach, Prentice Hall, 2001.

6. Prediction of protein structure and the principles of protein conformation by Fasman, G.D. New York. Plenum Press, 1989.

7. Computational methods for protein folding : advances in chemical physics vol. 120 by Friesner, R.A. Ed., Prigogine, L. Ed. & Rice, S.A.New York. John wiley & sons, Inc. publication, 2002.

8. Neural Networks: A Comprehensive Foundation (2nd Edition) by Simon Haykin.

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(MBI-304) Biological Database Management

Objectives: • To be able to understand the concepts of data, data models and relationships. • To be aware of various data representation techniques and various types of databases. 1. Introduction Database designing, data capturing; Data Abstraction, Data Models, Instances & Schemes; Textual Databases; Introduction to Distributed Database Processing. Basic concepts and applications of Network Data Model, Hierarchical Data Model, Multimedia Databases E-R Model – E-R diagrams; Entity and entity sets; Relations and relationship sets; Reducing E-R Diagrams to tables. Basic concepts of – Indexing and Hashing; ISAM; B+ Tree indexed files; Static Hash functions; Dynamic Hash functions 2. ORACLE, SQL Oracle Architecture Oracle objects - Tables, Views, Indexes, Sequences; Synonyms, Snapshots, Clusters Database - Table space, Data files, Blocks, Extents, Segments; Oracle Background Processes, control files; Oracle Memory Management; Rollback Segments; Redo logs/Archival; Security, Grants, Roles, Privileges Oracle Utilities & SQL *DBA - Oracle Server Manager; Export-Import/SQL Monitor Backup & Recovery (Archiving); Physical Storage & Logical Storage. Oracle * Reports - Reports Features; Full Integration with Forms and Graphics; Data Model and layout editors. Layout Objects - Frames, Repeating Frames, Fields, Boiler Plate, Anchor; Interface Components; Report Formats; Example Reports; Single Query, Multi Query, Matrix, Master-Detail etc.; User Defined Columns; PL/SQL Interface/ Triggers; Packaged Procedure; Calling Report from a Form. Menu - Default Menus; Custom Menus; Menu Objects; Menu Module, Main Menu, Individual Menus, Sub Menus, Menu Items; Menu Editor, PL/SQL in Menu Modules, Menu Security. Select Statements, Data Definition Statements, Data Manipulation Statements, Data Control Statements. 3. More on SQL SQL commands used to create table, modify table structure, drop table, rename table. SQL commands used to change the data within the database – inserting of records in the tables, updation of all or specific set of records in tables, viewing the attributes of table’s column. Querying data – Selecting the data from table using Arithmetic and logical Operators, Range searching and pattern matching, Function, group function,

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scalar function. Defining Constraints – Types: I/O constraints like Primary Key, Foreign key, Null and Unique constraints. Business constraints like check constraints. Levels: Table level constraints, column level constraints, creating and deletion of constraints using the Alter Table clause. Joining multiple tables, joining a table to itself. Security Management using SQL – Granting rights on user objects such as Tables, Views, and Sequences; Revoking rights on user objects such as Tables, Views, and Sequences. 4. PL/SQL PL/SQL blocks; Database triggers Handling with cursors in PL/SQL blocks; Types of cursors: Implicit and Explicit cursors. 5. Introduction to Front-end application development Introduction to Front-end application development, working with code and forms, variables, procedures and controlling program executor, standard controls, data access. . Establishing connection to various databases. Need of metadata standards & ontology.

Reference Books:

1. SQL, PL/SQL: the programming language of oracle by I. Bayross, Ed. 2, New Delhi. BPB Publications, 2002.

2. Oracle SQL & PL/SQL Handbook: a guide for data administrators, developers, and business analysis (With CD) by J. Palinski, Delhi, Pearson Education, 2003.

3. Database System Concepts by Hanery Korth and Abraham Silberschatz, Tata 4. An Introduction to Database Systems by C.J. Date, Addison-Wesley. 5. ORACLE: Power Objects Handbook by Bruce Kolste, David Peterson.

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(MBI-401) Metabolomes and Metabolic Pathway Engineering

Objectives: • Learning the basic biochemical concepts of metabolic pathways • Understanding the role of Bioinformatics in the study of metabolic pathways • Learning the Bioinformatics-based approaches for predicting and engineering metabolic

pathways 1. Introduction Enzyme Nomenclature and Classification Major Metabolic Pathways: - Gluconeogenesis - Pentose phosphate pathway - Glycogen synthesis and degradation - Fatty acid oxidation and synthesis - Amino acid catabolism - Purine and pyrimidine nucleotide synthesis 2. Metabolic Pathways databases KEGG, PathDB EcoCyc and MetaCyc EMP Malaria Parasite Metabolic Pathways Boehringer Mannheim - Biochemical Pathways 3. Enzymes, Compounds and Reactions databases LIGAND - Biochemical Compounds and Reactions ENZYME - Enzymes BRENDA - Comprehensive Enzyme Information System 4. More on Metabolic Pathways Full Genome Annotation through knowledge of Metabolic Pathways Organism Specific Metabolic Pathways Comparison of Metabolic Pathways 5. Metabolic Pathway Engineering Mathematical modeling of metabolic pathways . Engineering of Metabolic Pathways Representation of Metabolic Pathways Generation and Dynamic Representation of Metabolic Pathways Deriving Common Principles from the Metabolic Pathways Knowledge - E.g. deriving sets of enzymes specific for various reactions (e.g. oxidation), Alternative paths for synthesis of metabolites etc. Reference Books:

1. Fundamentals of Biochemistry (2nd

edition) by D., Voet, Voet, J.G. & Pratt, C. W. John Wiley & Sons, 2006.

2. Lehninger Principles of Biochemistry (4th

edition) by D. L. Nelson & M. M. Cox, W. H. Freeman & Co, 2005.

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3. The Enzyme Reference by D. L. Purich & R. D. Allison (2002) Academic Press. IUBMBM,1992.

4. Enzyme Nomenclature, Academic Press, 2002. 5. Metabolic Engineering by G.N. Stephanopoulos, A. A. Aristidou & J. Nielsen

Academic Press, 2006. 6. Gene regulation and metabolism: postgenomic computational approaches. By

Collado-Vides, J. & Hofestadt, R. Cambridge, The MIT Press, 2002.

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(MBI-402) Programming in Perl Objectives: To upgrade the skills of the students in Perl programming essential for Bioinformatics 1. Introduction: What is Perl? Why use Perl in Bioinformatics? History of Perl, Availability,

Support, Basic Concepts 2. Scalar Data: What Is Scalar Data? Numbers, Strings, Scalar Operators, Scalar Variables,

Scalar Operators and Functions 3. Arrays and List Data: What Is a List or Array? Literal Representation, Variables, Array

Operators and Functions, Scalar and List Context 4. Control Structures: Statement Blocks 5. Hashes: What Is a Hash? Hash Variables, Literal Representation of a Hash, Hash

Functions, Hash Slices 6. BasicI/O 7. Regular Expressions: Concepts About Regular Expressions, Simple Uses of Regular

Expressions, Patterns, More on the Matching Operator, Substitutions, The split and joinFunctions

8. Subroutines: System and User Functions, The local Operator, Variable-length Parameter Lists, Notes on Lexical Variables

9. Miscellaneous Control Structures: 10. File handles and File Tests: What Is a File handle? Opening and Closing a File handle,

Using Pathnames and Filenames, A Slight Diversion: die, Using File handles, The -x File Tests, The stat Function

11. Formats: What Is a Format? Defining a Format, Invoking a Format 12. Directory Access: Moving Around the Directory Tree, Globbing, Directory Handles,

Opening and Closing a Directory Handle, Reading a Directory Handle File and Directory Manipulation 13. Process Management: Using system and exec, Using Backquotes, 14. Other Data Transformation: Finding a Substring, Extracting and Replacing a Substring 15. Formatting Data: Sorting, Transliteration 16. System Information: Getting User and Machine Information, Packing and Unpacking

Binary Data Getting Network Information 17. Database Manipulation: DBM Databases and DBM Hashes, Opening and Closing

DBM Hashes, Fixed-Length Random-Access Databases, Variable-Length (Text) Databases, Win32 Database Interfaces

18. CGI Programming: The CGI.pm Module, Your CGI Program in Context, Simplest CGI Program, Passing Parameters via CGI, Perl and the Web

19. Object oriented perl: Introduction to modules, Creating Objects 20. Bioperl: Introduction, Installation procedures, Architecture, Uses of bioperl Reference Books:

1. Beginning Perl for Bioinformatics by James Tisdall, O-Reilly. 2. Learning Perl by Randal L. Schwartz, Tom Phoenix, O-Reilly. 3. Programming Perl by Larry Wall, Tom Christiansen, Jon Orwant, O-Reilly. 4. Advanced Perl Programming by Sriram Srinivasan, O-Reilly.

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(MBI-403) Comparative Genomics and Proteomics Objectives: • Appreciate the importance of full genome comparisons • Understand and appreciate the full genome comparative studies of viruses, microbes, pathogens

and eukaryotes • Understand and explore the comparative genomics databases • Understand the concepts of SNPs and their significance • Understand and appreciate the proteomics concepts and technology • Understand the basis and nature of protein-protein interactions and related databases 1. Objective and Overview of Genome Comparisons 2. GenomeAlignments

BLAST2 MUMmer PipMaker VISTA

3. Comparison of Gene Order GeneOrder

4. Comparative Genomics Viruses Microbes Pathogens Eukaryotes

5. Comparative Genomics Databases COG VirGen CORG HOBACGEN Homophila XREFdb Gramene

6. Single Nucleotide Polymorphism, dbSNP and other SNP-related databases 7. Overview of Proteomics

Experimental Techniques Bioinformatics Approaches

8. Protein-Protein Interaction Networks, databases and software DIP (Database of Interacting Proteins) PPI Server BIND - Biomolecular Interaction Network Database PIM -Hybrigenics PathCalling Yeast Interaction Database MINT - a Molecular Interactions Database\ GRID - The General Repository for Interaction Datasets InterPreTS - protein interaction prediction through tertiary structure

Reference Books:

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1. Comparative genomics: empirical and analytical approaches to gene order dynamics, map alignment and the evolution of gene families by Sankoff, D. & Nadeau, J.H., Netherlands, Kluwer Academic Publishers, 2000.

2. Bioinformatics: sequence and genome analysis by David Mount, cold springer harbour press, 2004.

3. Introduction to proteomics: tools for the new biology by Liebler, D.C. & Yates, J.R. III, New York. Humana Press, 2002.

4. Proteomics: from protein sequence to function by Pennington, S. R. & Dunn, M. J.: New Delhi, Viva Books Private Ltd, 2002.

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(MBI-404) Genome to Drug and Vaccine

Objectives: • Appreciate and understand the changes in the approaches for computational analysis between

the pre- and post-genomic era. • Understand the role of Bioinformatics in the genome sequencing process and post genomic

analyses for gene identification, full genome comparison, structural and functional elucidation of genomes, drug target identification etc.

• Appreciate the role of Bioinformatics in post-genomics technologies and areas such as DNA micro-array experiments, Proteomics, protein-protein interactions, pharmacogenetics, identification of disease genes, drug and vaccine design etc.

1. Overview of genome sequencing: strategies & approaches 2. GenomeAssembly 3. Genome Databases and related data resources (EST, STS, GSS, HSS etc.)

Nature and types of data Organization of data in databases; OMIM Genome Data Visualization (With emphasis on Human Genome)

4. Tools for Genomic Data Mining Basic Aspects of Genome Annotation Database Search Engines: Special tools for searching genomic data Prediction of ORFs and Genes; Gene Modeling Prediction of Signal sequences (Promoters, Primers, splice sites, UTRs etc.),

Operons 5. Identification of Disease Genes (in the context of Human Genetics and Genetics of Model Animals)

Identification of Drug Targets Metabolic diseases and Pathogenic diseases Gene Expression Analysis Structural Genomics Functional Genomics

6. Pharmacokinetics Classification Case study Comparative screening ADMET: Drug metabolism; Role of cytochromes P450; Elimination half-life;

Toxicity screening Pharmacogenetics The genetics of drug metabolism The genetics of therapeutic targets Interactions of small molecules and gene-based drug targets Proteome analysis and Prediction of epitopes on Genomic scale

Reference Books:

1. Guide to Human Genome Computing by Martin J. Bishop, Academic Press. ISBN 0-12-102051-7.

2. From Genome to Therapy: Integrating new technologies with drug development by Novartis Foundation, John Wiley. ISBN 0-471-62744-5.

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3. Bioinformatics - from genomes to drugs (vol. 1), basic technologies (vol.1) by Lengauer, T., Germany, Wiley-VCH, 2002.

4. Bioinformatics approach Guide to the analysis of genes and proteins by Andceas Baxevanis and B.F. Francis Ouellettee. John Wiley 2004.

5. Genome mapping and sequencing By Ian Dunham, Horizon, ISBN1-898486-50-6.

6. The Genome by Ram S. Verma, VCH, ISBN 1-56081-043-2.

Project should be based on the following topics 1. Parasite bioinformatics 2. Biodiversity informatics 3. Microbial informatics 4. Immunology bioinformatics 5. Plant bioinformatics 6. Molecular modeling 7. Any recent advance topic.

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Question Paper pattern_ M.Sc. Examination

Bioinformatics

(Paper Code)

(Paper Name)

------------------------------------------------------------------------------------------------------------ Time: Three Hours Maximum Marks: 50 N.B.: - (i) All questions carry equal marks. (ii) Draw neat-labeled diagrams wherever necessary. (iii) Assume data wherever necessary. Q1: 10

Or 10 Q2: 10

Or 10 Q3: 10

Or 10 Q4: 10

Or 10 Q5: Short notes (any two) 10 a. b. c. d. NOTE: There will be annual practical exam at the end of first and second year. But the practical should be conducted in respective semesters.