Homol-MetReS is a web application framework that allow users to efficiently compare molecular circuits between any number of organisms with permitting functional (re)annotation of proteomes, in context of identifying a protein that are involved in the process(es) of interest, that have the similar function or sets of proteins those linked in processes.

1. Hiren Karathia, PhD scholar
Dept. de Ciències Mèdiques Bàsiques,
University of Lleida
Spain.

2.  Motivation for implementation of Homol-
MetReS.
 Homol-MetReS.
 Case study: Saccharomyces cerevisiae.
 Conclusion.
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3. To understand,
(A). How a given organism responds at the molecular level
to a given stimulus?
(B). What protein entities mediate the response?
(C). How do those molecular entities interact to coordinate
the response?
(D). How to answer these questions for any given organism?
Laboratory experiments on each and every
organism are not feasible!
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4. In silico alternative
 Identify networks of proteins responsible for a
given process/response.
 Compare the networks in silico, to identify
organism(s) with similar networks.
 Use the comparison to choose an appropriate
model organism to study process.
[Karathia et al., PLoS ONE, 2011].
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5.  No user-friendly tools are available to apply
the approach described in the previous slide.
 Having such a tool could be very useful for
anyone who wants to apply that approach.
 Therefore we designed and implemented
such a web application, Homol-MetReS.
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6.  Motivation for implementation of Homol-
MetReS.
 Homol-MetReS.
 Case study: Saccharomyces cerevisiae.
 Conclusion.
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7. Design requirements
(1). Management system that stores and manages molecular information for each
organisms, including:
(a). Protein/Gene Sequence.
(b). Functions/processes assigned to the sequence.
(2). Re-annotation module to allow any user to (re)assign functions to proteins or
genes (e. g. GO, EC Numbers, KEGG pathways, or user defined etc.).
(3) Integration module to allow any user to correlate different types of classifications.
(4). Method that can establish evolutionary relationships between
two organisms at the sequence homology scale.
(5). Visualization tools, to analyze the results.
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8. Homol-MetReS is such a web implemented tool that integrates
different applications to fulfill various independent tasks, in an
integrated way, as follows:
1. Manage whole proteome of your selected model organism.
2. Automatically and/or manual classification of the proteome into various biological
components.
3. Compare the proteome of your selected organism to those of more than 1000 other
organisms.
4. Automatically discriminating compared proteomes into orthologs, in-
paralogs, homologues and absent.
5. Provide graphical representation and textual analysis of proteome comparisons.
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9. MySQL
ZOPE BLAST
&
Python
Mathematica
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10. Model organism’s Annotation
whole proteome
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11. Model organism’s Comparison
whole proteome
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12. P1 P2 … Pn Model Organism’s Proteome
Other N number of Organism’s Proteome
P1
O1
D P1 P2 … Pm Cluster of orthologs
O2
H
O1 O2
… Om
P1 P2 … Pm
Cluster of homologs
H1 H2 … Hm
…….
P1 P2 … Pm
Cluster of domain
D1 D2 … Dm orthologs
Cluster of absent
P1 P2 … Pm
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13. Cluster of orthologs
Cluster of Cluster of Cluster of Cluster of
One-to-One One-to-Many Many-to-One Many-to-Many
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15. Model Org-2 …. …. …. …. …. Org-m
Org-1
Prot-1 1 1 1 1 1 1 1 1
Prot-2 1 0 Enzymes Susbtrate 1 Interaction
1 1 1 1
… 1
Bio-proc
Prot-3 1 1
Prot-1 0
1 0 2 1 3 1 02 1 2
… 1 0
Prot-2 1
2 0 0 0 6 1 01 0 1
… 1 1
Prot-3 0 1 3 0 8 1 1 1 3
The smaller the Hamming Distance between
0 1
Prot-n 1 … 1
the two vectors, the more similar the 1 2
0
1 1 2 0 1 0 0
0
function/process is in both organisms.
… 0 0 0 0 0
Prot-n 2 0 0 0 0
Calculate Hamming Distance (HD)
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16.  Motivation for implementation of Homol-
MetReS.
 Homol-MetReS.
 Case study: Saccharomyces cerevisiae.
 Conclusion.
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17. Saccharomyces cerevisiae functional reannotation
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18. Bulk annotated components Functional annotation
Green square - indicates a high level of
coincidence between the set of proteins
Organisms
included in specific components in a model
organism and the corresponding set in other
organism.
Red square - indicates complete absence of
the set of proteins involved in the specific
function/process (column) in a given
organism (row) with respect to the same
function/process in the Model organism.
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19. Biological Process
annotation
Organisms
Biological processes
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20.  Motivation for implementation of Homol-
MetReS.
 Homol-MetReS.
 Case study: Saccharomyces cerevisiae.
 Conclusion.
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21. Homol-MetReS provides a framework to:
Simplify functional classification and annotation of proteomes in new
organisms.
Facilitate correlation between different functional classification
schemes.
Discriminate orthologs, homologs and duplicated genes for a given
functional term, using sequence comparisons between any number
of organisms.
Do functional comparisons of full proteomes between any number of
organisms enabling a systems biology perspective of how the
organisms may work.
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