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PHYLOPAT: AN UPDATED VERSION OF THE PHYLOGENETICPATTERN DATABASE CONTAINS GENE NEIGHBORHOOD
Presenter: Reihaneh RabbanyPresented in Bioinformatics Course (CMPUT 606),
Instructed by Prof. Guohui Lin,
Computing Science Department,
University of Alberta,
Winter 2009
Tim Hulsen et.al., Nucleic Acids Research, 2009, Vol. 37, Database issue
INTRODUCTION
Phylogenetic patterns Show the presence or absence of certain
genes in a set of whole genome sequencesCan be used to determine sets of genes
that occur only in certain evolutionary branches
More Common as increasing amounts of orthology data have become available
Phylogenetic Patterns Search tools are available for querying proteins, but not for querying genes
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PHYLOPAT
PhyloPat is a database which offers the possibility of querying the Ensembl database using any phylogenetic pattern
Functionalities : Gene neighborhood view Anticorrelating patterns Support of Entrez ‘ Gene IDs Direct sequence retrieval of members of a
phylogenetic lineage
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ENSEMBL Human genome
3 billion base-pairs 35,000 genes
The genome alone is of little use Locations and relationships of individual genes
Manual annotation Ensembl
Ensembl (freely accessible) Sequence data is fed into a software "pipeline“ Creates a set of predicted gene locations Saves them in a MySQL database
Originally focus on Human Now includes mouse, fruitfly, zebrafish, plants, fungi,
…
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PHYLOPAT - DATABASE CONTENT A set of phylogenetic lineages Complete set of orthologies Collected
All 39 species’ genes in Ensembl 741 species pairs 815 452 genes 19 010 478 orthologous relationships
11 446 546 one-to-one 4 588 300 one-to-many 2 975 632 many-to-many
Ensembl ortholog detection pipeline Similarity values by
Best reciprocal hits and best score ratio (WU BLASTP) Graph of gene relations and Clustering Multiple alignment (MUSCLE ) Phylogenetic tree (TreeBeST ) Orthologous relationships 5
PHYLOPAT - DATABASE CONSTRUCTION
Generating phylogenetic lineages Determining evolutionary order
Using the NCBI Taxonomy Phylogenetic tree Phylogenetic lineages
For each gene in the first species Look for orthologs in the other species Add all orthologs to the phylogenetic lineage Check for orthologs themselves, until no additional
orthologies were found for any of the genes
Repeat for all genes in all 39 species that were not yet connected to any phylogenetic lineage 6
WEB APPLICATION
A web interface Query the PhyloPat MySQL database
Phylogenetic lineages Phylogenetic patterns
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OMNIPRESENT - OLIGOPRESENT - POLYPRESENT GENES Omnipresent
Genes present in all 39 species phylogenetic pattern
‘11111111111111111111111111111111111111’ (or MySQL regular expression ‘^1+$’)
688 omnipresent genes Which most likely have important functions, since they
are present in all species. Oligopresent
Genes that exist in only one or two species Which species are evolutionary most related
Polypresent Genes that are missing in only one or two
species Measure for evolutionary relatedness
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ANTICORRELATING PATTERNS
Patterns that are exactly opposite Phylogenetic lineages with anticorrelating
patterns can be functionally completely different, but could also be highly similar in function ‘00000000000000001011100111100111111001
0’ ‘11111111111111110100011000011000000110
1’These genes can be analogous i.e.
performing a similar function without being evolutionary related. 9
GENE NEIGHBORHOOD
Inferring ‘true’ orthology Orthologous conservation of gene neighborhood Human gene ENSG00000134398
Has two predicted orthologs in chimpanzee: gene ENSPTRG00000007893 gene ENSPTRG00000009535
Only correspond to the gene neighborhoods of gene ENSPTRG00000007893, for nine of the nearest neighbors
Inferring functional annotation Build hypotheses about the processes or
pathways that genes might be involved in10
FASTA-FORMAT SEQUENCE FILES
Both the pattern search output and the gene neighborhood view contain links to FASTA files of the peptide sequences
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DISCUSSION AND CONCLUSION
PhyloPat is useful in Orthology detection Evolutionary studies Gene annotation
Complex Queries It is possible to determine
A species set that should be included (1), A species set that should be excluded (0) A species set which presence is indifferent (*)
Using of regular expression queries Easy-to-use web interface Relies only on one database (Ensembl)
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DISCUSSION AND CONCLUSION (CONT.)
Gene neighborhood view Locating evolutionary-related genomic clusters of
genes Detecting the ‘true orthologs’ within large sets of
predicted orthologs Functional annotating less well known genes
PhyloPat will be updated with each major Ensembl release to ensure up-to-date and reliable phylogenetic lineages (species added)
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LINEAGE INFORMATION OF PP000255
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QUESTIONS
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