Bioinformatics

Neha BarveLecturer, Bioinformatics

School of Biotechnology, DAVVIndore

Topics covered

Introduction to Bioinformatics Area of Bioinformatics Fields Biological databases Sequence analysis

What Is Bioinformatics?

Bioinformatics is the unified discipline formed from the combination of: Biology, Computer science, and Information technology.

"The mathematical, statistical and computing methods that aim to solve biological problems using DNA and amino acid sequences and related information.“ –Frank Tekaia

Area

Algorithms, Databases and information

systems, Artificial intelligence and

soft computing, Information and

computation theory, Modeling and simulation,

Generating new knowledge of biology and medicine, and improving & discovering new models of computation (e.g. DNA computing, neural computing, evolutionary computing, immuno-computing, cellular-computing).

Related fields of Bioinformatics

Related Fields:Computational Biology

The study and application of computing methods for classical biology

Primarily concerned with evolutionary, population and theoretical biology, rather than the cellular or molecular level

Related Fields:Medical Informatics

The study and application of computing methods to improve communication, understanding, and management of medical data

Generally concerned with how the data is manipulated rather than the data itself

Related Fields:Cheminformatics

The study and application of computing methods, along with chemical and biological technology, for drug design and development

Related Fields:Genomics

Analysis and comparison of the entire genome of a single species or of multiple species

A genome is the set of all genes possessed by an organism

Genomics existed before any genomes were completely sequenced, but in a very primitive state

Related Fields:Proteomics

Study of how the genome is expressed in proteins, and of how these proteins function and interact

Concerned with the actual states of specific cells, rather than the potential states described by the genome

Related Fields:Pharmacogenomics

The application of genomic methods to identify drug targets

For example, searching entire genomes for potential drug receptors, or by studying gene expression patterns in tumors

Related Fields:Pharmacogenetics

The use of genomic methods to determine what causes variations in individual response to drug treatments

The goal is to identify drugs that may be only be effective for subsets of patients, or to tailor drugs for specific individuals or groups

Genomics

Classic Genomics Post Genomic era

Comparative Genomics Functional Genomics Structural Genomics

What is Genomics?

Genome complete set of genetic instructions for

making an organism Genomics

any attempt to analyze or compare the entire genetic complement of a species

Early genomics was mostly recording genome sequences

What next?

Post Genomic era Comparative Genomics Functional Genomics Structural Genomics

What Is Proteomics?

Proteomics is the study of the proteome—the “PROTEin complement of the genOME”

More specifically, "the qualitative and quantitative comparison of proteomes under different conditions to further unravel biological processes"

What Makes Proteomics Important?

All cells in an organism contain the same DNA. This DNA encodes every possible cell type in

that organism—muscle, bone, nerve, skin, etc. If we want to know about the type and state of a

particular cell, the DNA does not help us, in the same way that knowing what language a computer program was written in tells us nothing about what the program does.

What Makes Proteomics Important?

There are more than 160,000 genes in each cell, only a handful of which actually determine that cell’s structure.

Many of the interesting things about a given cell’s current state can be deduced from the type and structure of the proteins it expresses.

Changes in, for example, tissue types, carbon sources, temperature, and stage in life of the cell can be observed in its proteins.

Proteomics In Disease Treatment

Nearly all major diseases—more than 98% of all hospital admissions—are caused by an particular pattern in a group of genes.

Isolating this group by comparing the hundreds of thousands of genes in each of many genomes would be very impractical.

Looking at the proteomes of the cells associated with the disease is much more efficient.

Proteomics In Disease Treatment

Many human diseases are caused by a normal protein being modified improperly. This also can only be detected in the proteome, not the genome.

The targets of almost all medical drugs are proteins. By identifying these proteins, proteomics aids the progress of pharmacogenetics.

Examples

What do these have in common? Alzheimer's disease Cystic fibrosis Mad Cow disease An inherited form of emphysema Even many cancers

Biological databases

Data: any fact and statistics which has some useful information and used for analysis.

Biological system has tremendous data and it is difficult to maintain this much amount in paper

So need of a system to store and manipulate it.

Definition A biological database is a collection of data that is

organized so that its contents can easily be accessed, managed, and updated. The activity of preparing a database can be divided in to:

· Collection of data in a form which can be easily accessed

· Making it available to a multi-user system ( always available for the user)

The biological information of nucleic acids is available as sequences while the data of proteins is available as sequences and structures. Sequences are represented in single dimension where as the structure contains the three dimensional data of sequences.

Biological databases It is a library of scientific information. Which type of data?

DNA (sequence) RNA Protein (sequence, structure, functions, annotations, localiztion etc) Chemical (structure, reactions, assays) Literature Enzymes (Functions) Signaling pathways (prok, euk.) Evolutionary (Phylogenetics) Clinical

From where this data come from: Experimentations (genome sequencing, structure

determination, chemical reactions) Literatures (scientific research papers) Computational analysis (predictions)

Need: Make it available to researcher all over the world Development / storage updation To make biological data available in computer-readable form.

Types

Primary Secondary Based on type of data

Sequence databases (protein/ nucleic acid) Structure database Enzyme database Signaling pathway Interaction databases (PPI/PDI)

04/24/23 14:07

Different classifications of databases….

Primary or derived databases Primary databases: experimental results directly into

database Secondary databases: results of analysis of primary

databases Aggregate of many databases

Links to other data items Combination of data Consolidation of data

Data types:•Relationships between

sequence 3D structure protein functions

•Properties and evolution of genes, genomes, proteins, metabolic pathways in cells

•Use of this knowledge for prediction, modelling, and design

TDQAAFDTNIVTLTRFVMEQGRKARGTGEMTQLLNSLCTAVKAISTAVRKAGIAHLYGIAGSTNVTGDQVKKLDVLSNDLVINVLKSSFATCVLVTEEDKNAIIVEPEKRGKYVVCFDPLDGSSNIDCLVSIGTIFGIYRKNSTDEPSEKDALQPGRNLVAAGYALYGSATMLV

Nucleic acid EMBL GenBank DDBJ (DNA Data Bank of

Japan)

Examples of databases

Primary: (Nucleic acid) DDBJ EMBL GeneBank(Protein) PIR MIPS SWISS-PROT TrEMBL

Secondary: PROSITE Pfam TrEMBL FSSP HSSP Etc………

Genebank

GenBank is the NIH genetic sequence database of all publicly available DNA and derived protein sequences, with annotations describing the biological information these records contain.

EMBL/GenBank/DDJB These 3 db contain mainly the same information (few

differences in the format and syntax) Serve as archives containing all sequences (single genes,

ESTs, complete genomes, etc.) derived from: Genome projects and sequencing centers Individual scientists Patent offices (i.e. USPTO, EPO)

Non-confidential data are exchanged daily There are approximately 126,551,501,141 bases in 135,440,924

sequence records in the traditional GenBank divisions and 191,401,393,188 bases in 62,715,288 sequence records in the WGS division as of April 2011.

Sequences from > 50,000 different species;

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GenBank

DDBJEMBL

EMBLEMBL

Entrez

SRS

getentry

NIGNIGCIB EBI

NCBI

NIHNIH

•Submissions•Updates

•Submissions•Updates

•Submissions•Updates

Each database store data in specific file format.

For e.g. genbank file format Embl file format Ddbj file format

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GenBank Flat File (GBFF)LOCUS MUSNGH 1803 bp mRNA ROD 29-AUG-1997DEFINITION Mouse neuroblastoma and rat glioma hybridoma cell line NG108-15 cell TA20 mRNA, complete cds.ACCESSION D25291NID g1850791KEYWORDS neurite extension activity; growth arrest; TA20.SOURCE Murinae gen. sp. mouse neuroblastma-rat glioma hybridoma cell_line:NG108-15 cDNA to mRNA. ORGANISM Murinae gen. sp. Eukaryotae; mitochondrial eukaryotes; Metazoa; Chordata; Vertebrata; Mammalia; Eutheria; Rodentia; Sciurognathi; Muridae; Murinae.REFERENCE 1 (sites) AUTHORS Tohda,C., Nagai,S., Tohda,M. and Nomura,Y. TITLE A novel factor, TA20, involved in neuronal differentiation: cDNA cloning and expression JOURNAL Neurosci. Res. 23 (1), 21-27 (1995) MEDLINE 96064354REFERENCE 3 (bases 1 to 1803) AUTHORS Tohda,C. TITLE Direct Submission JOURNAL Submitted (18-NOV-1993) to the DDBJ/EMBL/GenBank databases. Chihiro Tohda, Toyama Medical and Pharmaceutical University, Research Institute for Wakan-yaku, Analytical Research Center for Ethnomedicines; 2630 Sugitani, Toyama, Toyama 930-01, Japan (E-mail:CHIHIRO@ms.toyama-mpu.ac.jp, Tel:+81-764-34-2281(ex.2841), Fax:+81-764-34-5057)COMMENT On Feb 26, 1997 this sequence version replaced gi:793764.FEATURES Location/Qualifiers source 1..1803 /organism="Murinae gen. sp." /note="source origin of sequence, either mouse or rat, has not been identified" /db_xref="taxon:39108" /cell_line="NG108-15" /cell_type="mouse neuroblastma-rat glioma hybridoma" misc_signal 156..163 /note="AP-2 binding site" GC_signal 647..655 /note="Sp1 binding site" TATA_signal 694..701 gene 748..1311 /gene="TA20" CDS 748..1311 /gene="TA20" /function="neurite extensiion activity and growth arrest effect" /codon_start=1 /db_xref="PID:d1005516" /db_xref="PID:g793765" /translation="MMKLWVPSRSLPNSPNHYRSFLSHTLHIRYNNSLFISNTHLSRR KLRVTNPIYTRKRSLNIFYLLIPSCRTRLILWIIYIYRNLKHWSTSTVRSHSHSIYRL RPSMRTNIILRCHSYYKPPISHPIYWNNPSRMNLRGLLSRQSHLDPILRFPLHLTIYY RGPSNRSPPLPPRNRIKQPNRIKLRCR" polyA_site 1803BASE COUNT 507 a 458 c 311 g 527 tORIGIN 1 tcagtttttt tttttttttt tttttttttt tttttttttt tttttttttg ttgattcatg 61 tccgtttaca tttggtaagt tcacaggcct cagtcaacac aattggactg ctcaggaaat 121 cctccttggt gaccgcagta tacttggcct atgaacccaa gccacctatg gctaggtagg 181 agaagctcaa ctgtagggct gactttggaa gagaatgcac atggctgtat cgacatttca 241 catggtggac ctctggccag agtcagcagg ccgagggttc tcttccgggc tgctccctca 301 ctgcttgact ctgcgtcagt gcgtccatac tgtgggcgga cgttattgct atttgccttc 361 cattctgtac ggcattgcct ccatttagct ggagagggac agagcctggt tctctagggc 421 gtttccattg gggcctggtg acaatccaaa agatgagggc tccaaacacc agaatcagaa 481 ggcccagcgt atttgtaaaa acaccttctg gtgggaatga atggtacagg ggcgtttcag 541 gacaaagaac agcttttctg tcactcccat gagaaccgtc gcaatcactg ttccgaagag 601 gaggagtcca gaatacacgt gtatgggcat gacgattgcc cggagagagg cggagcccat 661 ggaagcagaa agacgaaaaa cacacccatt atttaaaatt attaaccact cattcattga 721 cctacctgcc ccatccaaca tttcatcatg atgaaacttt gggtcccttc taggagtctg 781 cctaatagtc caaatcatta caggtctttt cttagccata cactacacat cagatacaat 841 aacagccttt tcatcagtaa cacacatttg tcgagacgta aattacgggt gactaatccg 901 atatatacac gcaaacggag cctcaatatt ttttatttgc ttattccttc atgtcggacg 961 aggcttatat tatggatcat atacatttat agaaacctga aacattggag tacttctact 1021 gttcgcagtc atagccacag catttatagg ctacgtcctt ccatgaggac aaatatcatt 1081 ctgaggtgcc acagttatta caaacctcct atcagccatc ccatatattg gaacaaccct 1141 agtcgaatga atttgagggg gcttctcagt agacaaagcc accttgaccc gattcttcgc 1201 tttccacttc atcttaccat ttattatcgc ggccctagca atcgttcacc tcctcttcct 1261 ccacgaaaca ggatcaaaca acccaacagg attaaactca gatgcagata aaattccatt 1321 tcacccctac tatacatcaa agatatccta ggtatcctaa tcatattctt aattctcata 1381 accctagtat tatttttccc agacatacta ggagacccag acaactacat accagctaat 1441 ccactaaaca ccccacccca tattaaaccc gaatgatatt tcctatttgc atacgccatt 1501 ctacgctcaa tccccaataa actaggaggt gtcctagcct taatcttatc tatcctaatt 1561 ttagccctaa tacctttcct tcatacctca aagcaacgaa gcctaatatt ccgcccaatc 1621 acacaaattt tgtactgaat cctagtagcc aacctactta tcttaacctg aattgggggc 1681 caaccagtag acacccattt attatcattg gccaactagc ctccatctca tacttctcaa 1741 tcatcttaat tcttatacca atctcaggaa ttatcgaaga caaaatacta aaattatatc 1801 cat//

Features (AA seq)

DNA Sequence

Header•Title•Taxonomy•Citation

GenBank file format

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Accession.version

LOCUS, Accession, gi and PIDLOCUS HSU40282 1789 bp mRNA PRI 21-MAY-1998DEFINITION Homo sapiens integrin-linked kinase (ILK) mRNA, complete cds.ACCESSION U40282VERSION U40282.1 GI:3150001

CDS 157..1515 /gene="ILK" /note="protein serine/threonine kinase" /codon_start=1 /product="integrin-linked kinase" /protein_id="AAC16892.1" /db_xref="PID:g3150002" /db_xref="GI:3150002"

LOCUS: HSU40282 ACCESSION: U40282 VERSION: U40282.1 GI: 3150001 PID: g3150002 Protein gi: 3150002 protein_id: AAC16892.1 Protein_idprotein gi

ACCESSIONLOCUS

PIDgi

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Which Tool? BankIt: Web based tool which is simple, easy

to use, great for simple submissions, but not ideal for complicated ones. Sakura (DDBJ) WebIn (EMBL)

Sequin: Client that you need to d/l to your computer, a little harder to learn, but has great documentation, and ideal for complicated, large, multiple submissions.

tbl2asn: ideal for batch records, command line, scriptable, can work with sequin

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Which tool?mRNA Genomic

EST Other Other STS/GSS HTGS

dbEST Simple •Better control of annotations•pop/phylo•segmented sets

Simple dbSTSdbGSS

Customized software or tbl2asn

WWWBankIt

WWWBankIt

E-mailor FTP

E-mailor FTP

E-mailor FTP

Sequinor tbl2asn

E-mail

Protein databases

•SWISS-PROT: Annotated Sequence Database•TrEMBL: Database of EMBL nucleotide translated sequences•InterPro:Integrated resource for protein families, domains and functional sites.•CluSTr:Offers an automatic classification of SWISS-PROT and TrEMBL.Etc………..

Swiss prot It is a high quality annotated and non-redundant protein

sequence database, which brings together experimental results, computed features and scientific conclusions.Since 2002, it is maintained by the UniProt consortium and is accessible via the UniProt website.

Statistics: Release 2011_12 of 14-Dec-11 of UniProtKB/Swiss-Prot contains 0.5 million sequence entries, comprising 189261966 amino acids abstracted from 205244 references. 629 sequences have been added since release 2011_11, the sequence data of 146 existing entries has been updated and the annotations of 182184 entries have been revised.

Structure database PDB An Information

Portal to Biological Macromolecular Structures

As of Tuesday Dec 20, 2011 there are 78020 Structures

NMR X-ray Electron microscopy

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HEADER LEUCINE ZIPPER 15-JUL-93 1DGC 1DGC 2 COMPND GCN4 LEUCINE ZIPPER COMPLEXED WITH SPECIFIC 1DGC 3 COMPND 2 ATF/CREB SITE DNA 1DGC 4 SOURCE GCN4: YEAST (SACCHAROMYCES CEREVISIAE); DNA: SYNTHETIC 1DGC 5 AUTHOR T.J.RICHMOND 1DGC 6 REVDAT 1 22-JUN-94 1DGC 0 1DGC 7 JRNL AUTH P.KONIG,T.J.RICHMOND 1DGC 8 JRNL TITL THE X-RAY STRUCTURE OF THE GCN4-BZIP BOUND TO 1DGC 9 JRNL TITL 2 ATF/CREB SITE DNA SHOWS THE COMPLEX DEPENDS ON DNA 1DGC 10 JRNL TITL 3 FLEXIBILITY 1DGC 11 JRNL REF J.MOL.BIOL. V. 233 139 1993 1DGC 12 JRNL REFN ASTM JMOBAK UK ISSN 0022-2836 0070 1DGC 13 REMARK 1 1DGC 14 REMARK 2 1DGC 15 REMARK 2 RESOLUTION. 3.0 ANGSTROMS. 1DGC 16 REMARK 3 1DGC 17 REMARK 3 REFINEMENT. 1DGC 18 REMARK 3 PROGRAM X-PLOR 1DGC 19 REMARK 3 AUTHORS BRUNGER 1DGC 20 REMARK 3 R VALUE 0.216 1DGC 21 REMARK 3 RMSD BOND DISTANCES 0.020 ANGSTROMS 1DGC 22 REMARK 3 RMSD BOND ANGLES 3.86 DEGREES 1DGC 23 REMARK 3 1DGC 24 REMARK 3 NUMBER OF REFLECTIONS 3296 1DGC 25 REMARK 3 RESOLUTION RANGE 10.0 - 3.0 ANGSTROMS 1DGC 26 REMARK 3 DATA CUTOFF 3.0 SIGMA(F) 1DGC 27 REMARK 3 PERCENT COMPLETION 98.2 1DGC 28 REMARK 3 1DGC 29 REMARK 3 NUMBER OF PROTEIN ATOMS 456 1DGC 30 REMARK 3 NUMBER OF NUCLEIC ACID ATOMS 386 1DGC 31 REMARK 4 1DGC 32 REMARK 4 GCN4: TRANSCRIPTIONAL ACTIVATOR OF GENES ENCODING FOR AMINO 1DGC 33 REMARK 4 ACID BIOSYNTHETIC ENZYMES. 1DGC 34 REMARK 5 1DGC 35 REMARK 5 AMINO ACIDS NUMBERING (RESIDUE NUMBER) CORRESPONDS TO THE 1DGC 36 REMARK 5 281 AMINO ACIDS OF INTACT GCN4. 1DGC 37 REMARK 6 1DGC 38 REMARK 6 BZIP SEQUENCE 220 - 281 USED FOR CRYSTALLIZATION. 1DGC 39 REMARK 7 1DGC 40 REMARK 7 MODEL FROM AMINO ACIDS 227 - 281 SINCE AMINO ACIDS 220 - 1DGC 41 REMARK 7 226 ARE NOT WELL ORDERED. 1DGC 42 REMARK 8 1DGC 43 REMARK 8 RESIDUE NUMBERING OF NUCLEOTIDES: 1DGC 44 REMARK 8 5' T G G A G A T G A C G T C A T C T C C 1DGC 45 REMARK 8 -10 -9 -8 -7 -6 -5 -4 -3 -2 -1 1 2 3 4 5 6 7 8 9 1DGC 46 REMARK 9 1DGC 47 REMARK 9 THE ASYMMETRIC UNIT CONTAINS ONE HALF OF PROTEIN/DNA 1DGC 48 REMARK 9 COMPLEX PER ASYMMETRIC UNIT. 1DGC 49 REMARK 10 1DGC 50 REMARK 10 MOLECULAR DYAD AXIS OF PROTEIN DIMER AND PALINDROMIC HALF 1DGC 51 REMARK 10 SITES OF THE DNA COINCIDES WITH CRYSTALLOGRAPHIC TWO-FOLD 1DGC 52 REMARK 10 AXIS. THE FULL PROTEIN/DNA COMPLEX CAN BE OBTAINED BY 1DGC 53 REMARK 10 APPLYING THE FOLLOWING TRANSFORMATION MATRIX AND 1DGC 54 REMARK 10 TRANSLATION VECTOR TO THE COORDINATES X Y Z: 1DGC 55 REMARK 10 1DGC 56 REMARK 10 0 -1 0 X 117.32 X SYMM 1DGC 57 REMARK 10 -1 0 0 Y + 117.32 = Y SYMM 1DGC 58 REMARK 10 0 0 -1 Z 43.33 Z SYMM 1DGC 59 SEQRES 1 A 62 ILE VAL PRO GLU SER SER ASP PRO ALA ALA LEU LYS ARG 1DGC 60 SEQRES 2 A 62 ALA ARG ASN THR GLU ALA ALA ARG ARG SER ARG ALA ARG 1DGC 61 SEQRES 3 A 62 LYS LEU GLN ARG MET LYS GLN LEU GLU ASP LYS VAL GLU 1DGC 62 SEQRES 4 A 62 GLU LEU LEU SER LYS ASN TYR HIS LEU GLU ASN GLU VAL 1DGC 63 SEQRES 5 A 62 ALA ARG LEU LYS LYS LEU VAL GLY GLU ARG 1DGC 64 SEQRES 1 B 19 T G G A G A T G A C G T C 1DGC 65 SEQRES 2 B 19 A T C T C C 1DGC 66 HELIX 1 A ALA A 228 LYS A 276 1 1DGC 67 CRYST1 58.660 58.660 86.660 90.00 90.00 90.00 P 41 21 2 8 1DGC 68 ORIGX1 1.000000 0.000000 0.000000 0.00000 1DGC 69 ORIGX2 0.000000 1.000000 0.000000 0.00000 1DGC 70 ORIGX3 0.000000 0.000000 1.000000 0.00000 1DGC 71 SCALE1 0.017047 0.000000 0.000000 0.00000 1DGC 72 SCALE2 0.000000 0.017047 0.000000 0.00000 1DGC 73 SCALE3 0.000000 0.000000 0.011539 0.00000 1DGC 74 ATOM 1 N PRO A 227 35.313 108.011 15.140 1.00 38.94 1DGC 75 ATOM 2 CA PRO A 227 34.172 107.658 15.972 1.00 39.82 1DGC 76

ATOM 842 C5 C B 9 57.692 100.286 22.744 1.00 29.82 1DGC 916 ATOM 843 C6 C B 9 58.128 100.193 21.465 1.00 30.63 1DGC 917 TER 844 C B 9 1DGC 918 MASTER 46 0 0 1 0 0 0 6 842 2 0 7 1DGC 919 END 1DGC 920

PDB HEADER COMPND SOURCE AUTHOR DATE JRNL REMARK SEQRES ATOM COORDINATES

Other databases

Pathway databases Enzyme databases Ligand databases Motif, domain databases etc…………..

Sequence analysis

term sequence analysis refers to the process of subjecting a DNA, RNA or peptide sequence to any of a wide range of analytical methods to understand its features, function, structure, or evolution.

Need The comparison of sequences in order to find

similarity often to infer if they are related (homologous) Identification of intrinsic features of the sequence such

as active sites, post translational modification sites, gene-structures, reading frames, distributions of introns and exons and regulatory elements

Identification of sequence differences and variations such as point mutations and single nucleotide polymorphism (SNP) in order to get the genetic marker.

Revealing the evolution and genetic diversity of sequences and organisms

Identification of molecular structure from sequence alone

Types

Pair wise sequence alignment (two sequnces e.g. BLAST)

Multiple sequence alignment (more than two e.g. ClustalW, Tcoffee, MUSCLE etc )

Algorithms for sequence alignment

Needleman Wunsch algorithm Smithwaterman algorithms BLAST FASTA

Needleman Wunsch algorithm Used for global alignment Used to align protein and nucleotide sequences Dynamic programming (complex to similar)A divide-and-conquer strategy: Break the problem into smaller subproblems. Solve the smaller problems optimally. Use the sub-problem solutions to construct an optimal solution for the original problem.The Needleman-Wunsch algorithm consists of three steps: 1. Initialization of the score matrix 2. Calculation of scores and filling the traceback matrix 3. Deducing the alignment from the traceback matrix

APPLICATIONS

Profile comparison (all sequences of a family)

Gene prediction Annotation Homology modelling (Protein Structure

Prediction) Primer designing

Applications of bioinformatics Molecular medicine Gene therapy Drug development Microbial genome

applications Waste cleanup Climate change Studies Alternative energy

sources Biotechnology Vetinary Science

Antibiotic resistance Forensic analysis of

microbes Bio-weapon creation Evolutionary studies Crop improvement Insect resistance Improve nutritional quality Development of Drought

resistance varieties

Classification

Protein sequence databases: UniProt Universal Protein Resource (UniProt Consortium: EBI,

Expasy, PIR) PIR Protein Information Resource (Georgetown University Medical

Center (GUMC)) Swiss-Prot Protein Knowledgebase (Swiss Institute of

Bioinformatics) PEDANT Protein Extraction, Description and ANalysis Tool

(Forschungszentrum f. Umwelt & Gesundheit) PROSITE Database of Protein Families and Domains DIP Database of Interacting Proteins (Univ. of California) Pfam Protein families database of alignments and HMMs (Sanger

Institute) PRINTS PRINTS is a compendium of protein fingerprints

(Manchester University) ProDom Comprehensive set of Protein Domain Families

(INRA/CNRS)