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ULB contribution to the MICROME Jamboree

Evry, June 27, 2011

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Tools used for ULB contrib to MICROME

From the Regulatory Sequence Analysis Tools (RSAT, http://rsat.ulb.ac.be/rsat/). infer-operons: predict operons from genome annotations footprint-discovery

• Gene-wise prediction of cis-regulatory elements by detecting conserved motifs in promoters of orthologous genes (phylogenetic footprints).

• Inference of a co-regulation network by linking pairs of genes with similar footprints.

Network Analysis Tools (RSAT, http://rsat.ulb.ac.be/neat/). pathway builder: extract a sub-network of a large metabolic networks (all reactions

and compounds) that connects at best a set of seed nodes (e.g. enzymes in the same operon).

compare-classes: comparison between two files describung grouping of elements (e.g. genes) into sets (e.g. operon members), classes (e.g. GO), clusters (e.g. co-expression), etc ...

• Pathway projection: comparison between annotated pathways and genome reaction content.

• Patwhay comparison: comparison between predicted and annotated pathways.

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From operons to pathways

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Operon prediction Example: Bacillus subtilis

http://rsat.ulb.ac.be/MICROME/results/operons/Bacillus_subtilis/Bacillus_subtilis_operons_inferred_dist55_2genes.html

We selected all the predicted operons containing at least 2 genes (single-gene transcription units are not reported).

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Examples of 1-to-1 operon/pathway correspondances

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Exercise: filling the gap

An operon from B.subtilis contains 4 enzyme-coding genes.

Those enzymes catalyze inter-connected reactions.

The pathway builder inferred 2 possible candidates as intermediates.

Can we use annotations to check the gap filling ?

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Predicting pathways from operons

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Case study: purine operon(s) The pur operon was splitted in 3 pieces by infer-operons, because some genes pairs have a larger spacing.

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Pathway projections

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All METACYC pathways against genome-wise reaction sets Results

http://rsat.ulb.ac.be/MICROME/results/pathway_projections/projection_against_metacyc/result_index.html Tool: compare-classes Approach: compare the set of all “possible” reactions in a given organism (enzyme-coding gene found

in genome or spontaneous reaction) with all pathways annotated in Metacyc. Stats: coverage + hypergeometric significance Detailed output: lists of reactions found and missing for each pathway. Example: Bacillus subtilis

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Pathway projection profiles (D4.4)

Each row represents one pathway Each column represents one organism Separate sheets are generated to show the absolute and relative coverage, significance, ...

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Pathway projection tree (D4.4)

The projections profiles can be mapped onto a taxonomic tree, using the tool GeneTrace (Victor Kunin and Christos Ouzounis).

Each intermediate node is annotated with the number of pathways found (green). Each branch is annotated with the number of lost pathways (blue) or gained

pathways (red).

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Prediction of co-regulated genes

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Detection of conserved motifs in promoters of orthologs

Example of footprint-discovery result http://rsat.ulb.ac.be/MICROME/results/footprints/Enterobacteriales/Escherichia_coli_K12/NP_416992.1/NP_416992.1_Escherich

ia_coli_K12_Enterobacteriales_ortho_dyads_3nt_sp0-20-2str-noov_taxfreq_sig0.png