Introduction to Bioinformatics
Subhadip Basu, Ph.D.
Department of Computer Science and Engineering,
Jadavpur University,
Kolkata, INDIA
Email: subhadip@[Link]
Course Objectives
• To introduce the bioinfomatics discipline
• To make the students familiar with the major
biological questions which can be addressed
by bioinformatics tools
• To introduce the major tools used for
sequence and structure analysis and explain
in general how they work (limitation etc..)
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What is Bioinformatics?
“The field of science in which biology, computer
science, and information technology merge to form a
single discipline”
Ultimate goal: to enable the discovery of new
biological insights as well as to create a global
perspective from which unifying principles in biology
can be discerned.
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Central Paradigm in Molecular
Biology
Gene (DNA) mRNA Protein
21ST centaury
Genome Transcriptome Proteome
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Complete Genomes
2010 2005
Total 1379 294
Eukaryotes 133 39
Bacteria 1152 235
Archaea 94 23
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1,000 Genomes Project: Expanding the
Map of Human Genetics
Researchers hope the effort will speed up
the discovery of many diseases's genetic
roots
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25000 genomes… What’s Next
The “post-genomics”
era
Annotation Comparative Functional Systems
genomics genomics Biology
Main Goal:
To understand the living
cell 7
From ….25000 genomes
To…Understanding living cells
Annotation
CCTGACAAATTCGACGTGCGGCATTGCATGCAGACGTGCATG
CGTGCAAATAATCAATGTGGACTTTTCTGCGATTATGGAAGAA
CTTTGTTACGCGTTTTTGTCATGGCTTTGGTCCCGCTTTGTTC
AGAATGCTTTTAATAAGCGGGGTTACCGGTTTGGTTAGCGAGA
AGAGCCAGTAAAAGACGCAGTGACGGAGATGTCTGATG CAA
TAT GGA CAA TTG GTT TCT TCT CTG AAT ......
.............. TGAAAAACGTA
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Identify the genes within a
given sequence of DNA
Identify the sites
Which regulate the gene
Annotation
Predict the function
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How do we identify a gene
in a genome?
A gene is characterized by several features (promoter, ORF…)
some are easier and some harder to detect…
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Using Bioinformatics approaches for Gene hunting
Relative easy in simple organisms (e.g. bacteria)
VERY HARD for higher organism (e.g. humans)
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Comparative
genomics
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Perhaps not surprising!!!
How humans
are chimps?
Comparison between the full drafts of the human and chimp genomes
revealed that they differ only by 1.23%
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So where are we different ??
Human ATAGCGGGGGGATGCGGGCCCTATACCC
Chimp ATAGGGGGGATGCGGGCCCTATACCC
Mouse ATAGCGGGATGCGGCGCTATACCA
Human ATAGCGGGGGGATGCGGGCCCTATACCC
Chimp ATAGGGG--GGATGCGGGCCCTATACCC
Mouse ATAGCG---GGATGCGGCGC-TATACC-A
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And where are we similar ???
VERY VERY SIMAILAR
DIFFERENT Conserved between
many organisms
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Functional
genomics
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TO BE IS NOT ENOUGH
In any time point a gene can be functional or not
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From the gene expression pattern we can lean:
What does the gene do ?
When is it needed?
What other genes or proteins interact with it?
…..
What's wrong??
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Systems
Biology
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Biological networks
Jeong et al. Nature 411, 41 - 42 (2001)
What can we learn from
Biological Networks
What can we
learn about this
protein
• Is the protein essential for the organism ?
• Is it a good drug targets?
Biological Databases
The different types of data are collected in
database
– Sequence databases
– Structural databases
– Databases of Experimental Results
All databases are connected
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Sequence databases
• Gene database
• Genome database
• Disease related mutation database
• ………….
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Genome Browsers
Easy “walk” through the genome
UCSC Genome Browser
[Link]
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Disease related database
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Sickle Cell Anemia
• Due to 1 swapping an A for a T, causing inserted amino
acid to be valine instead of glutamine in hemoglobin
Image source: [Link]
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Healthy Individual
>gi|28302128|ref|NM_000518.4| Homo sapiens hemoglobin, beta (HBB), mRNA
ACATTTGCTTCTGACACAACTGTGTTCACTAGCAACCTCAAACAGACACCATGGTGCATCTGACTCCTGA
GGAGAAGTCTGCCGTTACTGCCCTGTGGGGCAAGGTGAACGTGGATGAAGTTGGTGGTGAGGCCCTGGGC
AGGCTGCTGGTGGTCTACCCTTGGACCCAGAGGTTCTTTGAGTCCTTTGGGGATCTGTCCACTCCTGATG
CTGTTATGGGCAACCCTAAGGTGAAGGCTCATGGCAAGAAAGTGCTCGGTGCCTTTAGTGATGGCCTGGC
TCACCTGGACAACCTCAAGGGCACCTTTGCCACACTGAGTGAGCTGCACTGTGACAAGCTGCACGTGGAT
CCTGAGAACTTCAGGCTCCTGGGCAACGTGCTGGTCTGTGTGCTGGCCCATCACTTTGGCAAAGAATTCA
CCCCACCAGTGCAGGCTGCCTATCAGAAAGTGGTGGCTGGTGTGGCTAATGCCCTGGCCCACAAGTATCA
CTAAGCTCGCTTTCTTGCTGTCCAATTTCTATTAAAGGTTCCTTTGTTCCCTAAGTCCAACTACTAAACT
GGGGGATATTATGAAGGGCCTTGAGCATCTGGATTCTGCCTAATAAAAAACATTTATTTTCATTGC
>gi|4504349|ref|NP_000509.1| beta globin [Homo sapiens]
MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLG
AFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVAN
ALAHKYH
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Diseased Individual
>gi|28302128|ref|NM_000518.4| Homo sapiens hemoglobin, beta (HBB), mRNA
ACATTTGCTTCTGACACAACTGTGTTCACTAGCAACCTCAAACAGACACCATGGTGCATCTGACTCCTGA
GGTGAAGTCTGCCGTTACTGCCCTGTGGGGCAAGGTGAACGTGGATGAAGTTGGTGGTGAGGCCCTGGGC
AGGCTGCTGGTGGTCTACCCTTGGACCCAGAGGTTCTTTGAGTCCTTTGGGGATCTGTCCACTCCTGATG
CTGTTATGGGCAACCCTAAGGTGAAGGCTCATGGCAAGAAAGTGCTCGGTGCCTTTAGTGATGGCCTGGC
TCACCTGGACAACCTCAAGGGCACCTTTGCCACACTGAGTGAGCTGCACTGTGACAAGCTGCACGTGGAT
CCTGAGAACTTCAGGCTCCTGGGCAACGTGCTGGTCTGTGTGCTGGCCCATCACTTTGGCAAAGAATTCA
CCCCACCAGTGCAGGCTGCCTATCAGAAAGTGGTGGCTGGTGTGGCTAATGCCCTGGCCCACAAGTATCA
CTAAGCTCGCTTTCTTGCTGTCCAATTTCTATTAAAGGTTCCTTTGTTCCCTAAGTCCAACTACTAAACT
GGGGGATATTATGAAGGGCCTTGAGCATCTGGATTCTGCCTAATAAAAAACATTTATTTTCATTGC
>gi|4504349|ref|NP_000509.1| beta globin [Homo sapiens]
MVHLTPVEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLG
AFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVAN
ALAHKYH
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Structure Databases
• 3-dimensional structures of proteins,
nucleic acids, molecular complexes etc
• 3-d data is available due to techniques such
as NMR and X-Ray crystallography
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Databases of Experimental Results
• Data such as experimental microarray
images- gene expression data
• Proteomic data- protein expression data
• Metabolic pathways, protein-protein
interaction data, regulatory networks
• ETC………….
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Literature Databases
PubMed
[Link]
Service of the National Library of Medicine
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Putting it all Together
• Each Database contains specific
information
• Like other biological systems also these
databases are interrelated
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PROTEIN
DISEASE
PIR
LocusLink ASSEMBLED
SWISS-PROT GENOMES
OMIM
GoldenPath
OMIA
WormBase
MOTIFS
TIGR
BLOCKS
Pfam
Prosite
GENOMIC DATA
GenBank
ESTs DDBJ GENES
dbEST EMBL RefSeq
unigene AllGenes
SNPs GENE
GDB
dbSNP EXPRESSION
PATHWAY Stanford MGDB
KEGG NetAffx
STRUCTURE COG ArrayExpress
PDB
LITERATURE
MMDB
PubMed
SCOP
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