Bioinformatics Today
Prof. A.S. Kolaskar
Advisor
National Knowledge Commission
Data Escalation
• Full genome sequences
– Prokaryotes
~350
– Eukaryotes
~125
– Viruses
~2,000
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Proteomes
Microarray data
3-D Structures
Metabolomes
~50
~80
~2,500
~10
~50 TB
Doubles every
Twelve Months
Data Explosion in Biology
Metabolic
Pathways
Pharmacogenomics
Proteins
Medical Data Growth
Human
Genome
Petabytes
of
Data
SNPs
Combinatorial
Chemistry
External Research Partnerships
HTS
The Internet
Growth in Clinical Trials
ESTs
Mergers and Acquisitions
1990
2000
2004
Biodiversity Information System
• Species2000 Database
– Species 2000 & Integrated Taxonomic
Information System (IT IS) have assembled 37
taxonomic databases - 880,000 species
Also available on a free CD-ROM.
• Real time access to the Species 2000 array
of 26 online taxonomic databases
- 450,000 species
Indian Bioresource Information
Network (IBIN)
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Jeevsampada
Sasyasampada
Matsyasampada
Plants of India
Microbial Species Information System
Forest Resource Information System
Matsya Sampada
Fresh water Fin Fishes and Shell Fishes: Data on
1849 species include literature, distribution,
common name, coloration, images, synonyms,
remarks, references, morphology, economic
importance, size etc. and the datasets are collated
at National Bureau of Fish Genetic Resources,
Lucknow.
Searching Matsyasampada
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Vernacular Search
Scientific Search
Major Category
Chosen – Vernacular Search
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Search a vernacular name
Select Language – Maharashtra
Drop down menu: Marathi names of all the fish
Chosen - Shingat
Information Available
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Classification
Common names
Synonym
Images
Distribution
Morphology
References
Taxonomic
Information
Taxonomic Heirarchy
SuperOrder
Ostariophysi
Order
Siluriformes
Class
Actinopterygii
SubClass
Neopterygii
Order
Family
Siluriformes
Bagridae
SubFamily
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Genus
Mystus
Species
montanus
Shingat
• You are looking for 'Mystus montanus‘
• Common Names
– English Wynaad Mystus
– Kerala Vari kallencoori
– Maharashtra Shingat
Morphology (Mystus Montanus)
• Morphology Body elongate and compressed, its depth
about 5 times in standard length. Head depressed; occipital
process narrow, about 4 times as long as broad, reaching to
basal bone of dorsal fin; median longitudinal groove on
head not extending to occipital process
• Color In life, silvery above with a tinge of yellow along
abdomen; a silvery line along the flank terminating in a
dark spot at base of caudal fin, one or two light bands
along the side above lateral line; a bluish spot on shoulder.
Fins tinged with green
• Finformulae D 7; A iii 9; PI 6; Vi 5
• Fishery This species which attains a length of 15 cm, is of
minor interest to fisheries
Synonyms
Synonyms
References
Year
Bagrus
montanus
Jerdon
1849
Macrones
montanus
(Jerdon)
1849
Macrones
montanus
dibrugarensis
Chaudhuri
1913
Mystus
montanus
(Jerdon)
1849
Mystus vittatus
dibrugarensis
(Chaudhuri)
1913
References
Economic
Importance
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Author
Talwar and Jhingran
Book
Inland Fisheries vol.
2
Page no
Pg.567
Images
Distribution
Shingta
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You are looking for 'Mystus cavasius‘
Common Names
Andhra Pradesh Muti-jhella Nahara-jella Thella jella
Assam Barsingarah Singarah
Bihar Palwa Tengra
English Gangetic Mystus
Karnataka Nai-kirle
Maharashtra Katima Khirkirya Shingta
Orissa Guntea Kontia Tengra
Punjab Kinger
Tamil Nadu Cutta Nai-kelunti Solai-kelunti Vazhappu Vella- kellette
Uttar Pradesh Kala-tenguah Kavasi Shingti Singhara Tenguah
West Bengal Kabasi-tengra Tengra
Images
Distribution
Explore & Have Fun
http://www.ibin.co.in/
Understanding Biology using
Metabolic Pathways Database
Development of Metabolic Pathways and
related tools
• Some of the major metabolic pathway databases
are:
KEGG
Boehringer Mannheim
WIT
Ginsburg Malaria Database
BioCyc
PUMP-E
KEGG
KEGG LIMITATIONS
 Pathways are composites of pathways found
in many organism (Unclear what subpathways occur in specific organism)
 Static visualization
 No detailed information about enzymes
(inhibitors, subunits)
 No literature citations, no comments
Boehringer Mannheim
LIMITATIONS
 No query system
 Overloaded with information
WIT
Better representation but still
readability needs to be
improved
PUMP-E: Salient Features
• Dynamic Representation of pathways
• Dynamically building the organism-specific pathways from
genomic data
• Development of Software for
– Automated data updating (Perl scripts)
– Reformatting and organization of relevant information
from different databases
– Drawing pathways diagrams
– Comparison of pathways
– Visualization of ligands, enzymes
– Prediction of enzyme-substrate interactions
• URL-
http://202.41.70.51/mpe/
PUMP-E
Comparison of Metabolic Pathways
Case studies
Malarial parasite,
Mosquito & Human
Metabolome of Plasmodium falciparum
• Metabolic pathways of Plasmodium falciparum are known
to be stage-specific.
• Asexual blood-stage parasites depend on glycolysis and
conversion of pyruvate to lactate to derive energy.
• MS-MS studies carried out by Florens et.al(2002),
revealed that gametocyte and sporozoite stages of the
malarial parasite contain peptides of enzymes known to be
involved in mitochondrial TCA cycle and oxidative
phosphorylation.
In Plasmodium falciparum
Chromosomal locations of TCA cycle-enzymes
Enzyme
Chromosome
Hs
Ag
Pf
Citrate synthase
12
3L
10
Aconitase
22
3R
13
Isocitrate dehydrogenase
2
2L
13
Alpha-keto glutarate dehydrogenase (E1)
Alpha-keto glutarate dehydrogenase (E2)
7
14
2R
3L
8
13
Alpha-keto glutarate dehydrogenase (E3)
7
3L
12
Succinyl CoA ligase
13
2L
14
Succinate dehydrogenase (Cyt b560) (SDHA)
Succinate dehydrogenase ( Cyt b small) (SDHB)
Succinate dehydrogenase (flavoprotein) (SDHC)
1
11
5
3L
X
3L
10
Succinate dehydrogenase (iron-sulfur) (SDHD)
1
2L
12
Fumarase
Malate dehydrogenase
1*
7
2R*
3R
9**
6
• * Class II non-iron dependent Fumarase
• ** Class I iron-dependent Fumarase
Comparison of TCA cycle enzymes of
Plasmodium falciparum-Anopheles gambiae-Homo sapiens
Comparison of TCA cycle
90
80
70
60
50
40
30
20
10
0
Query:Human Database:
Anopheles
Query: Human Database:
Plasmodium
SD
SC
H_
oA
cy
tb
SD 560
H_
c
SD ytb
H_
fla
SD v o
H_
Fu iron
m
ar
as
e
M
DH
Ci
t_
sy
Ac
n
on
ita
se
IC
D
AK H
G
DH
1
AK
G
DH
2
AK
G
DH
3
Query: Anopheles Database:
Plasmodium
Enzyme
Plasmodium contains
only two SDH subunits
in contrast to 4 SDH
subunits in human &
anopheles
Fumarase class I is present
in Plasmodium whereas
Fumarase class II is present
in human & anopheles
TCA cycle: Comparison of proteome of
host,vector and parasite revealed…
• TCA cycle-specific enzymes of Homo sapiens and Anopheles gambiae
have high degree of sequence identity.
• Aconitase and Fumarase enzymes of Plasmodium falciparum show
very less similarity with their human and mosquito counterparts.
• An iron regulatory protein that has a C terminal domain similar to
Aconitase is present in Plasmodium and it likely carries out the function
of Aconitase enzyme.
• Fumarase (Class I) an iron-dependent enzyme is present in Plasmodium
whereas Fumarase (Class II), an non-iron dependent enzyme is present
in human and mosquito.
• Succinate dehydrogenase in Plasmodium contains only two subunits in
contrast to its human & mosquito counterparts, which have four
subunits.
Comparative Metabolomics Bacterial Identification
Total number of pathways in bacteria under study as per BioCyc 9.1
Organism name
Phylum
Genome Size
(Mbp)
Total number
of pathways
Agrobacterium tumefaciens
Bacillus anthracis
Bacillus subtilis
Caulobacter crescentus
Chlamydia trachomatis
Escherichia coli
Francisella tularensis
Haemophilus influenzae
Helicobacter pylori
Mycoplasma pneumoniae
Mycobacterium tuberculosis
CDC1551
Mycobacterium tuberculosis H37Rv
Shigella flexneri
Treponema pallidum
Vibrio cholerae
Proteobacteria
Firmicutes
Firmicutes
Proteobacteria
Chlamydiae
Proteobacteria
Proteobacteria
Proteobacteria
Proteobacteria
Firmicutes
Actinobacteria
Actinobacteria
Proteobacteria
Spirochaetes
Proteobacteria
5.673462
5.22729
4.21463
4.01695
1.04252
4.63968
1.89282
1.83014
1.66787
0.816394
4.40384
4.41153
4.6072
1.13801
4.03346
207
254
145
176
61
198
184
127
123
48
186
184
179
56
207
Pathways identical in all 15 bacteria under study w.r.t
E.coli
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Aspartate biosynthesis and degradation
Gluconeogenesis
Glycolysis
Pentose-Phosphate-Cycle
Purine nucleotides de novo biosynthesis I
De novo biosynthesis of pyrimidine ribonucleotides
Salvage pathway of adenine, hypoxanthine and their
nucleotides
• Salvage pathways of pyrimidine ribonucleotides
Importance of identical pathways
• Aspartate is a constituent of proteins and participates in several
biosyntheses pathways such as de novo biosynthesis of pyrimidine
ribonucleotide, purine nucleotide de novo biosynthesis I, NAD
biosynthesis I, pantothenate biosynthesis. Approximately 27 percent of
the cell's nitrogen flows through aspartate.
• Gluconeogenesis is a process by which glucose is generated. Glucose
is an important source of energy.
• Glycolysis is one of the most important metabolic processes. It is
known to be present in all types of organisms.
• Pentose-Phosphate-Cycle is one of the essential pathways of central
metabolism. This pathway is an important source of NADPH.
• Bases and nucleosides that are formed during degradation of RNA and
DNA can be recovered through salvage pathways, which can be
reconverted into nucleotides.
• All the above pathways are essential for survival of an organism
Pathways similar but not identical in all 15 bacteria under
study w.r.t E.coli
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Glycine biosynthesis I
TCA
FormylTHF biosynthesis I
Superpathway of biosynthesis of aspartate and
asparagine
• Colanic acid building blocks biosynthesis
Comparison of pathways with respect to E.coli
Organism name
Identical Similar
Pathways Pathways
Pathways Additional
Absent
Pathways
Agrobacterium tumefaciens (207)
Bacillus anthracis (254)
Bacillus subtilis (145)
Caulobacter crescentus (176)
Chlamydia trachomatis (61)
Francisella tularensis (184)
Haemophilus influenzae (127)
Helicobacter pylori (123)
Mycoplasma pneumoniae (48)
Mycobacterium tuberculosis CDC1551 (186)
Mycobacterium tuberculosis H37Rv (184)
Shigella flexneri (179)
Treponema pallidum (56)
Vibrio cholerae (207)
114
94
107
90
43
76
98
59
33
96
94
114
39
113
65
72
70
86
142
94
82
112
155
81
81
60
143
61
19
32
21
22
13
28
18
27
10
21
23
24
16
24
9
56
9
Hamming Distance Calculations
• Identical Pathways (0):
– Start and end products are identical;
intermediate steps are same.
• Similar Pathways (1):
– Start and end products are identical;
intermediate steps are different
• Pathways are absent (2):
– Start or end products are not same
Metabolic pathway path profile
Columns represents ‘n’ number of pathways and rows represent 15 bacteria under study. Each column
corresponds to a particular type of pathway. 2 denote pathway follows same path, 1 denotes pathway follows
different path while 0 denotes absence of pathway. This represents a part of the organism specific metabolic
pathway path profile.
Metabolic pathway path profile based tree
Acknowledgements
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Shweta Kohli
Manjari
Ms. Deshpande
Sangita Sawant