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Organization of Biological Data
and Databases
Pramod Wangikar
Dept. of Chemical Engineering
IIT Bombay
ORGANIZATION OF BIOLOGICAL DATA
Gene i
Genomics
m-RNA i
Transcriptomics
Protein i
Protein Sequence /
Proteomics
Function
(Enzyme,
hormone etc.)
3-D Structural
Database
Primary Structure of Deoxyribonucleic Acid (DNA)
A
C
3’
P
G
3’
P
5’
T
3’
P
5’
3’
P
5’
OR
pApCpGpTpTpG
OR
ACGTTG
G
T
3’
P
5’
3’
P
5’
OH
5’
The Basic Principle of Transcription
RNA
Polymerase
5’
Double
stranded
DNA
RNA
Nucleotides
The Code
• 64 ways of writing the codon
• 20 amino acids
M
uac 5'
5'... aug
F
gaa 5'
uuu ...
Adjacent mRNA codons
x=
Uxu
uxc
uxa
uxg
Cxu
cxc
cxa
cxg
u
c
F
L
Y
C
H
W
P
R
Q
N
I
S
T
C-S
K
R
M
NH+
gxu
gxc
gxa
gxg
g
S
axu
axc
axa
axg
a
D
V
A
G
O-
E
H:D/A
The Flow of Genetic Information
5’
DNA
Sequense same as RNA
3’
ACTGCACCATGGGGCTCAGCGACGGGGAATGGCACTTGGTG
TGACGTGGTACCCCGAGTCGCTGCCCCTTACCGTGAACCAC
Sequence complementary to RNA
mRNA 5’
ACUGCACCAUGGGGCUCAGCGACGGGGAAUGGCACUUGGUG
Initiation
signal
codons
Protein
Met-Gly-Leu-Ser-Asp-Gly-Gln-Trp-His-Leu-Val
Memory Requirements for Storing Genomes
00
01
10
11
Prokaryotic
Eukaryotic
=
=
=
=
a
c
g
t
0.5-7.0 Mbp
10 Mbp - 1000 Gbp
How Much Data Does a
Bacteria (E. coli) contain?
E. coli and Data size
Genome
Proteome
Sequence Structure
4.6 x 106 1.2 x 106 1.3 x 107
letters
letters,
atoms, atom
identifier, type, amino
description acid,
, location charge, 3
co-ordinates
per atom
1.1 Mbyte 10 Mbyte 400 Mbyte
Function
Substrate,
product,
reaction,
ligand,
specifcity,
transport
100 Mbyte
Metabolites
Structure Connection
800
Intercompound conversion
s, 10-50
of compds,
atoms,
reactions,
bonds, 3- rates,
coordinate enzymes
s per atom
50 Mbyte 500 Mb
Numbers are approximate: The data size increases roughly by
three orders of magnitude for human system
Minimal Life:
Self- assembly, Catalysis, Replication, Mutation, Selection
Environment
Monomers
RNA
Growth rate
Cell Boundary
Maximal Life:
Self- assembly, Catalysis, Replication, Mutation, Selection
Regulatory & Metabolic Networks
Metabolites
DNA
RNA
Protein
Growth rate
Expression
stem cells
cancer cells
microbes
Regulation: More biological data
What is regulation: A catalogue of possible scenarios
and respective course of action.
The information for regulation can be stored in the form of:
• Protein-protein interaction
• Protein-DNA interaction
• Protein-metabolite interaction
• Molecular switches, controls, set-points, etc.
Genome + Environment: Input file
Biological Machinery: Executable program
Observations: Output file
Can we crack the executable program?
Upstream activating
sequences (UAS)
Some useful regulatory signals on Genes
m-RNA expression
start & end
TATA box
DNA
x
x
mRNA
Ribosomal
binding site
protein
Protein
synthesis
starts
Protein
synthesis
stops
Minimal Gene Complement of Mycoplasma genitalium
DESCRIPTION OF A LIVING CELL / VIRUS
Genome /
Genomics
Transcriptomics
Proteomics /
Protein Map
General Capability
of the Cell
Readyness of the Cell
Physiological state
of the cell
Paradigm Shift in the Bioinformatics Age
Conventional Path
Function

Structure
Gene
Bioinformatics Age:
Gene
sequence
Protein Map
2D-PAGE,
pI, mol. wt.
Functional
Genomics
Structure
of Protein
Proteomics
Function
Possible Relationships Between Databases
Genome Sequence
Transcriptomics
Expression Profile
Protein-DNA
interactions
Proteomics
Protein Seqeunce
Protein Profile
Protein Structure
Protein-Protein
Interaction
Protein Function
Metabolome
Phenotype
Combinatorial Problems in Biology
•
Prediction of ORF; gene finding
•
Prediction of DNA regulatory sites
•
DNA regulatory Proteins
•
Protein-Protein interactions
•
Protein Function
•
Prediction of Metabolic capability
•
Prediction of Genetic Regulatory Circuits
Biological Databases
•
Raw databases
•
Processed databases
•
Querying in databases.
Raw Databases
Conventional Ones
DNA / Gene / Genome Sequence Databases.
EMBL, GenBank, GSDB etc.
> 106 genes, Doubles every 18 months.
Genome Projects: E. coli, plants, Human, Mouse, etc.
Protein Sequence Databases.
PIR, SwissProt, GenBank, etc.
> 105 protein sequences, Doubles every 21 months
Three Dimensional structure Database.
Brookhaven Protein Databank (PDB)
> 20,000 structures, doubles every 24 months.
Proteomics Database (SwissProt)
• Each Protein Identified by: pI, mol wt., mass spectra,
microsequencing, peptide mass fingerprint, etc.
• Entries for E.coli, yeast, human etc.
Hoogland et al, Nucl. Acids Res. (2000) 28, 286
Cluster of Orthologous Groups (COG) of Proteins:
A Processes Database
• Compares genes from different genomes.
• Forms clusters with similar sequences.
• Each COG contains genes connected through vertical
evolutionary descent.
• 30 genomes (68,571 genes), 2,791 COGs with 45,350 genes
• Assignment of function for genes based on known functions
for some members of the cluster.
• Highly useful for functional assignments for newly sequenced
genomes.
EcoCyc Database: Encyclopedia of E. coli genes and Metabolism
4300 genes, 695 enzymes, 595 reactions, 123 pathways
Blue: E. coli only; Green: both E. coli and H. influenzae.
Karp et al, Nucl. Acids Res. (1998) 26, 50
Querying in Databases
• Based on sequence similarity; gives similar
sequences and the similarity score or expectation
value.
• Normally a BLAST, FASTA search (local alignment).
Can look for a sequence motif.
• Gene names, biological source, functional category,
cellular location / role.
• Structural features (for known 3-D structures).
Bioinformatics:
A multidisciplinary effort is required
•
Generation of biological data
•
Storage and Retrieval of Data
•
Conversion of known biological hypotheses into
mathematical/statistical models
•
Building models from data
•
Fitting new data to existing models.
•
Searching for patterns in data
•
Derive new biological knowledge from Data