1, StarOmics course,Lausanne, Monday November 19th
Training agenda
2, StarOmics course,Lausanne, Monday November 19th
Outline
Part I:• Introduction• Data model
L-lysine biosynthesis• Pathway resources
UniPathway, KEGG, MetaCyc, Reactome, GO
Part II:• UniPathway tutorial
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Gene Ontology: biological processhttp://amigo.geneontology.orgKEGGhttp://www.genome.jp/kegg/compound MetaCychttp://metacyc.org Reactomehttps://www.reactome.orgUniPathwayhttp://www.unipathway.org…
Metabolic pathway resources
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– Dealing with the metabolic network as a whole is complex, and usage consists in decomposing the network into sub-parts, called metabolic pathways. Beside this pragmatic reason, another reason is that these pathways may be considered as elementary functional "modules" or building blocks. They can be combined, may have been conserved through evolution or may have evolved independently.
Metabolic pathways
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– Dealing with the metabolic network as a whole is complex, and usage consists in decomposing the network into sub-parts, called metabolic pathways. Beside this pragmatic reason, another reason is that these pathways may be considered as elementary functional "modules" or building blocks. They can be combined, may have been conserved through evolution or may have evolved independently.
– A metabolic pathway can be common to several organisms, meaning that the same set of reactions and enzyme families occurs in these organisms.
However, some deviations (alternative reactions) can be observed for a specific organism (or a group of organisms), leading to the notion of "variants”.
Metabolic pathways
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Variations in the biosynthesis of L-lysine
Yuchen Liu et al. J Bacteriol. 2010, 192:3304-3310.
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DAP pathway
Torruella et al. J Mol. Evol. 2009, 69:240-248.
AAA pathway
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L-lysine biosynthesis via DAP pathway L-lysine biosynthesis via AAA pathway
L-alpha-aminoadipate from 2-oxoglutarate
LL-2,6 diaminopimelate from(S)-tetrahydrodipicolinate
(acetylase route)
LL-2,6 diaminopimelate from(S)-tetrahydrodipicolinate(aminotransferase route)
LL-2,6 diaminopimelate from(S)-tetrahydrodipicolinate
(succinylase route)
L-lysine from DL-2,6 diaminopimelate
(S)-tetrahydrodipicolinate fromL-aspartate
DL-2,6-diaminopimelate fromLL-2,6diaminopimelate
DL-2,6-diaminopimelate from(S)-tetrahydrodipicolinate
L-alpha-aminoadipate from 2-oxoglutarate
L-lysine from L-alpha-aminoadipate(fungal route)
L-lysine from L-alpha-aminoadipate
(Thermus route)
L-lysine from L-alpha-aminoadipate
(Thermus route)
L-lysine biosynthesis
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DAP pathway
AAA pathway
L-Lysine
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variant I II III IV V VII 9 6 5 0 0 6II 10 5 0 0 6III 7 0 0 5IV 9 5 0V 10 0VI 7
Individual Amino Acids BiosynthesisLysine biosynthesis
• Lysine biosynthesis I• Lysine biosynthesis II • Lysine biosynthesis III • Lysine biosynthesis IV • Lysine biosynthesis V• Lysine biosynthesis VI
a
AAA pathway (2 variants)
DAP pathway (4 variants)
V
IV
I II III
VI c
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Gene Ontology: biological processhttp://amigo.geneontology.orgKEGGhttp://www.genome.jp/kegg/compound MetaCychttp://metacyc.org Reactomehttps://www.reactome.orgUniPathwayhttp://www.unipathway.org…
Metabolic pathway resources
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L-lysine biosynthesis via DAP pathway L-lysine biosynthesis via AAA pathway
L-alpha-aminoadipate from 2-oxoglutarate
LL-2,6 diaminopimelate from(S)-tetrahydrodipicolinate
(acetylase route)
LL-2,6 diaminopimelate from(S)-tetrahydrodipicolinate(aminotransferase route)
LL-2,6 diaminopimelate from(S)-tetrahydrodipicolinate
(succinylase route)
L-lysine from DL-2,6 diaminopimelate
(S)-tetrahydrodipicolinate fromL-aspartate
DL-2,6-diaminopimelate fromLL-2,6diaminopimelate
DL-2,6-diaminopimelate from(S)-tetrahydrodipicolinate
L-alpha-aminoadipate from 2-oxoglutarate
L-lysine from L-alpha-aminoadipate(fungal route)
L-lysine from L-alpha-aminoadipate
(Thermus route)
L-lysine from L-alpha-aminoadipate
(Thermus route)
L-lysine biosynthesis
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UniPathway concepts
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UCR03444: Left-to-Right direction is used in UER00029
UCR04371: Right-to-Left direction is used in UER00029
UER00028 (EC 2.3.3.14)= UCR00271 [LR]
UER00029 (EC 4.2.1.36)= UCR03444 [LR] + UCR04371 [RL]
+
ULS00012L-a-aminoadipate from 2-oxoglutarate
UCR00271: Left-to-Right direction is used in UER00028
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Protein-Reaction curation is performed in UniProt
UniPathway provides a structured controlled vocabulary for the annotation of pathway information within UniProtKB protein records.
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L-lysine biosynthesis via AAA pathway
UniPathway : label construction
An enzymatic reaction is labelled by its relative position in the sub-pathway : step n/m
step 1/4
step 2/4
step 3/4
step 4/4
L-alpha aminoadipate from 2-oxoglutarate
A sub-pathway is labelled by its terminal compounds :
product from substrate
A pathway is labelled by its terminal compound(s)“product biosynthesis” | “substrate degradation” [via xxx pathway]
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CC -!- PATHWAY: Amino-acid biosynthesis; L-lysine biosynthesis via AAACC pathway; L-lysine from L-alpha-aminoadipate (Thermus route): stepCC 5/5.
Acetyl-lysine deacetylase (T.thermophilus) (LYSK_THET2; Q8VUS5)
UniProt Headlineshttp://www.uniprot.org/news/2009/01/20/release
UPA00033 L-lysine via AAA pathway
UPA00402 Amino-acid biosynthesis
ULS00014 L-lysine from L-alpha-aminoadipate (Thermus route)
UER00039 step 5/5
CC-!-PATHWAY: super-pathway; pathway; sub-pathway: enzymatic-reaction.
UniPathway : label construction
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General annotation : Pathway link to UniPathway web site
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Pathway explorationhttp://www.unipathway.org
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Chemical view
Taxonomy view
Protein view
P1
P2
glutamine glutamate+
pyruvateO O
OO
O
CH2
OH H
H
O O
NH2
anthranilatechorismate
Molecular enzyme :TrpEDEnzyme classification : EC 4.1.3.27
Anthranilate synthase
How a given pathway is distributed into kingdoms, species,…?
Genomic view
genea geneb
How genes coding for the enzymes of a metabolic pathway are distributed into the genome?
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OBIWarehouse
TrEMBL reference proteomes
Swiss-Prot
UniPathway
Calculation
NCBI. RefSeq genomes
GeneOntology
Enzyme /IntEnz
Taxonomy. NCBI
Data update:sync. with UniProt releases
UniProtKB (part.)
RhEA
BioCyc Eco/MetaCyc
KEGG LIGAND
ChEBI
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UniProt complete proteomes
Protein view
Chemical view
Ontology view
PathwaySub-pathwayEnz-reaction
Genomic viewTaxonomy view
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UniPathway tutorial
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UniPathway short tour http://www.unipathway.org
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The home page is organized in 8 sections accessible through tabs
List of pathways for a given species
List of compounds used in UniPathway
List of pathways in UniPathway
Search UniPathway
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Quick search: lysine
Linear Sub-pathway: ULS
Pathway: UPA
Enzymatic-Reaction: UER
Action: Click on Quick search tabthen enter lysine in the UniPathway text field then click on Go button
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Browse pathway – compound - organism
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Table widget: known bug
if you encounter this error message just reload the web page
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Browse organism
Action: Enter ECOL then select ECOLI then click on Go button
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Browse organism provides the list of metabolic pathways for a selected organism
oscode=ECOLI
UniProtKB/Swiss-Prot annotation(reviewed)
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Action: Click again on Quick searchthen click on UPA00034 (L-lysine biosynthesis via DAP pathway)
Browse one pathway
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UniPathway: Pathway: Overview
tabs sections
Action: Click on map00300 to open the KEGG map with highlighted reactions
upid=UPA00034
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Lysine biosynthesis via DAP pathway in Acinetobacter
Click on ACIAD (Acinetobacter) – the scientific name is given in the tooltip
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UniPathway:Pathway: Genome view
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Thank you for your attention!
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