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Genomics
Functional associations Metabolic pathways Transcription
regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood
conservation Gene
Presence/Absence Comparing genomics
data Horizontal
comparative genomics
Vertical comparative genomics
Contents Genomics Functional associations
Metabolic pathways Transcription regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes
Gene Fusions Gene Neighborhood conservation Gene Presence/Absence
Comparing genomics data Horizontal comparative genomics
Conserved Co-expression Conserved Yeast-2-Hybrid
Vertical comparative genomics Evidence from multiple datasources Bayesian integration
Genomics
Functional associations Metabolic pathways Transcription
regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood
conservation Gene
Presence/Absence Comparing genomics
data Horizontal
comparative genomics
Vertical comparative genomics
Sequencing of genes and genomes
http://www.ncbi.nlm.nih.gov/genbank
Genomics
Functional associations Metabolic pathways Transcription regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood conservation Gene Presence/Absence Comparing genomics data Horizontal comparative genomics Vertical comparative genomics
Genome sequence of E. coliORIGIN
1 agcttttcat tctgactgca acgggcaata tgtctctgtg tggattaaaa aaagagtgtc
61 tgatagcagc ttctgaactg gttacctgcc gtgagtaaat taaaatttta ttgacttagg
121 tcactaaata ctttaaccaa tataggcata gcgcacagac agataaaaat tacagagtac
181 acaacatcca tgaaacgcat tagcaccacc attaccacca ccatcaccat taccacaggt
241 aacggtgcgg gctgacgcgt acaggaaaca cagaaaaaag cccgcacctg acagtgcggg
301 cttttttttt cgaccaaagg taacgaggta acaaccatgc gagtgttgaa gttcggcggt
361 acatcagtgg caaatgcaga acgttttctg cgtgttgccg atattctgga aagcaatgcc
421 aggcaggggc aggtggccac cgtcctctct gcccccgcca aaatcaccaa ccacctggtg
481 gcgatgattg aaaaaaccat tagcggccag gatgctttac ccaatatcag cgatgccgaa
541 cgtatttttg ccgaactttt gacgggactc gccgccgccc agccggggtt cccgctggcg
601 caattgaaaa ctttcgtcga tcaggaattt gcccaaataa aacatgtcct gcatggcatt
661 agtttgttgg ggcagtgccc ggatagcatc aacgctgcgc tgatttgccg tggcgagaaa
721 atgtcgatcg ccattatggc cggcgtatta gaagcgcgcg gtcacaacgt tactgttatc
781 gatccggtcg aaaaactgct ggcagtgggg cattacctcg aatctaccgt cgatattgct
841 gagtccaccc gccgtattgc ggcaagccgc attccggctg atcacatggt gctgatggca
901 ggtttcaccg ccggtaatga aaaaggcgaa ctggtggtgc ttggacgcaa cggttccgac
961 tactctgctg cggtgctggc tgcctgttta cgcgccgatt gttgcgagat ttggacggac
Genomics
Functional associations Metabolic pathways Transcription regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood conservation Gene Presence/Absence Comparing genomics data Horizontal comparative genomics Vertical comparative genomics
Complete genomes
What do we need them for? What can we use them for?
Visualization
How do genes make a complete cell?
Functions
Genomics
Functional associations Metabolic pathways Transcription
regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood
conservation Gene
Presence/Absence Comparing genomics
data Horizontal
comparative genomics
Vertical omparative genomics
For most genes in any genome we need function prediction
For many genes no function has been described
Even in a well-studied organism like E. coli only 43% have been characterized experimentally
Genomics
Functional associations Metabolic pathways Transcription regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood conservation Gene Presence/Absence Comparing genomics data Horizontal comparative genomics Vertical comparative genomics
Protein function Predicting
protein function
Levels of description
Homology for determining molecular function
Other aspect of function?
Genomics
Functional associations Metabolic pathways Transcription
regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood
conservation Gene
Presence/Absence Comparing genomics
data Horizontal
comparative genomics
Vertical comparative genomics
“Beyond” homology and molecular function
Homology based function prediction works very well, yet:
a large fraction of genes are poorly described (no homologs, uncharacterized homologs; this holds for ~60% of the human genes)
There are other aspects of function: functional associations, e.g. the target of a protein kinase or a transcriptional regulator, I.e. to understand the cell we need to know the interactions of the genes
Thus: predicting associations
Genomics
Functional associations Metabolic pathways Transcription
regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood
conservation Gene
Presence/Absence Comparing genomics
data Horizontal
comparative genomics
Vertical comparative genomics
PP
There are many types of functional associations (AKA functional interactions, interactions, functional links, functional relations) in molecular biology
Metabolic Pathways
Protein complexes
Transcription regulation
Cellular processes
Signaling
Genomics
Functional associations Metabolic pathways Transcription
regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood
conservation Gene
Presence/Absence Comparing genomics
data Horizontal
comparative genomics
Vertical comparative genomics
Types of functional associations
Filling gaps in metabolic pathways Genomics
Functional associations Metabolic pathways Transcription
regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood
conservation Gene
Presence/Absence Comparing genomics
data Horizontal
comparative genomics
Vertical comparative genomics
Types of functional associations
PP
Transcription regulation Signaling pathways Genomics
Functional associations Metabolic pathways Transcription
regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood
conservation Gene
Presence/Absence Comparing genomics
data Horizontal
comparative genomics
Vertical comparative genomics
Types of functional associations
Protein complexes Cellular process:
“DNA repair”
“Apoptosis”
Genomics
Functional associations Metabolic pathways Transcription
regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood
conservation Gene
Presence/Absence Comparing genomics
data Horizontal
comparative genomics
Vertical comparative genomics
Functionally associated proteins leave evolutionary traces of their relation in genomes
Genomics
Functional associations Metabolic pathways Transcription
regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood
conservation Gene
Presence/Absence Comparing genomics
data Horizontal
comparative genomics
Vertical comparative genomics
Gene fusion If two genes in another organism are fused
into one polypeptide A very reliable indicator for physical
interaction
Fusion
Genomics
Functional associations Metabolic pathways Transcription
regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood
conservation Gene
Presence/Absence Comparing genomics
data Horizontal
comparative genomics
Vertical comparative genomics
How to detect gene fusions?
Compare predicted protein sequences with each other using Homology searches 1. Find orthologs, Match
two complete orthologs to unmatched genes. - orthology definition
2. Find two complete homologs matching your gene. - More complicated rules.
Fusion
Genomics
Functional associations Metabolic pathways Transcription
regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood
conservation Gene
Presence/Absence Comparing genomics
data Horizontal
comparative genomics
Vertical comparative genomics
Orthology Common gene in
last common ancestor
Problems Duplication and loss Horizontal gene
transfer Methods
Bidirectional Best Hit Phylogenetic
reconstructions
A B
A1 A2 B1 B2
xx xx
Duplication
Speciation
A2B2
Duplication
Speciation
1
1 2
Genomics
Functional associations Metabolic pathways Transcription
regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood
conservation Gene
Presence/Absence Comparing genomics
data Horizontal
comparative genomics
Vertical comparative genomics
Gene order evolves rapidly Positional
mapping of orthologs between two species
Conservation of gene neighbors
Conserved operons (transcriptional units of more than one gene)
Genomics
Functional associations Metabolic pathways Transcription
regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood
conservation Gene
Presence/Absence Comparing genomics
data Horizontal
comparative genomics
Vertical comparative genomics
Conserved gene neighborhoodGenomics
Functional associations Metabolic pathways Transcription
regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood
conservation Gene
Presence/Absence Comparing genomics
data Horizontal
comparative genomics
Vertical comparative genomics
Comparison to associations in pathways: conservation implies a functional association
1
10
100
1000
10000
0 3 6 9 12
15
18
21
24
27
30
co-occurrences in operons
nu
mb
er
of
CO
Gs
0
1
2
3
4
5
6
avera
ge m
eta
bo
lic d
ista
ncenumber of
COGS
averagemetabolicdistance
Genomics
Functional associations Metabolic pathways Transcription regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood conservation Gene Presence/Absence Comparing genomics data Horizontal comparative genomics Vertical comparative genomics
Presence / absence of genes
L. Innocua (non-pathogen) L. monocytogenes (pathogen)
Genomics
Functional associations Metabolic pathways Transcription regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood conservation Gene Presence/Absence Comparing genomics data Horizontal comparative genomics Vertical comparative genomics
Presence / absence of genes
Differences in gene contentDifferences in metabolic Capacities?
Shared genes: shared metabolic capacities?It does not make sense to have just one member of a pathway.
Genomics
Functional associations Metabolic pathways Transcription regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood conservation Gene Presence/Absence Comparing genomics data Horizontal comparative genomics Vertical comparative genomics
Presence / absence of genes
L. Innocua (non-pathogen) L. monocytogenes (pathogen)
Pathogenicity genes?
Maybe not significant for one comparison, but maybe significant generalized over many genomes.
Genomics
Functional associations Metabolic pathways Transcription regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood conservation Gene Presence/Absence Comparing genomics data Horizontal comparative genomics Vertical comparative genomics
Phylogenetic profilesGenomics
Functional associations Metabolic pathways Transcription regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood conservation Gene Presence/Absence Comparing genomics data Horizontal comparative genomics Vertical comparative genomics
Context methods for prediction of functional associations
Benchmark with Kegg metabolic pathways
Integration into one score
0 0.2 0.4 0.6 0.8 1Score
0
0.2
0.4
0.6
0.8
1
FusionGene OrderCo-occurrenceF
ract
ion
sam
e K
EG
G m
a p (
Si)
Genomics
Functional associations Metabolic pathways Transcription regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood conservation Gene Presence/Absence Comparing genomics data Horizontal comparative genomics Vertical comparative genomics
How can you use this?
STRING Database No skills needed
Parse data yourself Some programming skills needed Orthologs
COG database Genomes
Genbank Genome Atlas Database
http://string.embl.de//
http://www.ncbi.nlm.nih.gov/COG/
http://www.ncbi.nlm.nih.gov/Genbank
http://www.cbs.dtu.dk/services
Genomics
Functional associations Metabolic pathways Transcription regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood conservation Gene Presence/Absence Comparing genomics data Horizontal comparative genomics Vertical comparative genomics
Correlated expression No operons in
eukaryotes Regulation by
the same transcription factors
Similarity in expression patterns in HTP expression data
High correlation between vectors
-1,5
-1
-0,5
0
0,5
1
1,5
Genomics
Functional associations Metabolic pathways Transcription regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood conservation Gene Presence/Absence Comparing genomics data Horizontal comparative genomics Vertical comparative genomics
N
i i
iN
iN
i i
i
YN
Y
XN
X
Nr
1
21
1
2 )(1
)(1
1
Correlated mRNA expression
Genes with correlated RNA expression often function in the same pathway.
Not reliable enough for function prediction.
Genomics
Functional associations Metabolic pathways Transcription regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood conservation Gene Presence/Absence Comparing genomics data Horizontal comparative genomics Vertical comparative genomics
Orthology predictionGenomics
Functional associations Metabolic pathways Transcription regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood conservation Gene Presence/Absence Comparing genomics data Horizontal comparative genomics Vertical comparative genomics
Total # of pairs
# of pairs > 0.6
Observed fraction > 0.6
Expected fraction > 0.6
Observed/Expected
Gene-pairs with an orthologous gene-pair > 0.6
Worm 18161 803 0.0442* 0.00379 12
Yeast 36548 1215 0.0332* 0.00216 15
Gene-pairs with a paralogous gene-pair > 0.6
Worm 207214
29031 0.1401* 0.00379 37
Yeast 38253 2167 0.0566* 0.00216 26
Low but significant levels of conservation of Low but significant levels of conservation of co-expressionco-expression(see Teichmann et al, TIBS 2002, Stuart et al., Science 2003)
van Noort et al, TIG, 2003Genomics
Functional associations Metabolic pathways Transcription regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood conservation Gene Presence/Absence Comparing genomics data Horizontal comparative genomics Vertical comparative genomics
Is the low level of conservation between Is the low level of conservation between S. S. cerevisiaecerevisiae and and C. elegansC. elegans of co-expression of co-expression (< 5%) “real”, reflecting evolution and (< 5%) “real”, reflecting evolution and species-specific interactions, or are we species-specific interactions, or are we just comparing noisy datasets ?just comparing noisy datasets ?
Species specific (idiosyncratic) coregulation:
“Efficient expression of the Saccharomyces cerevisiae
glycolytic gene ADH1 is dependent upon a cis-acting
regulatory element UASRPG found initially in genes
encoding ribosomal proteins.” Tornow and Santangelo,
Gene, 1990
Conservation of co-expressionGenomics
Functional associations Metabolic pathways Transcription regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood conservation Gene Presence/Absence Comparing genomics data Horizontal comparative genomics Vertical comparative genomics
High level of conservation of co-High level of conservation of co-regulation after speciationregulation after speciation
0
0.05
0.1
0.15
0.2
0.25
0.3
0.35
0.4
0.45
-0.5 -0.4 -0.3 -0.2 -0.1 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9
co-expression correlation (r)
freq
uenc
y di
stri
butio
n
worm orthologous gene pairs ofyeast gene pairs with r > 0.6and sharing TFBSall worm gene pairs
76 %
Genomics
Functional associations Metabolic pathways Transcription regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood conservation Gene Presence/Absence Comparing genomics data Horizontal comparative genomics Vertical comparative genomics
Conservation between orthologous pairs or Conservation between orthologous pairs or paralogous pairs increases the likelihood of paralogous pairs increases the likelihood of functional interactionfunctional interaction
van Noort et al, Trends Genet 2003van Noort et al, Trends Genet 2003
Genomics
Functional associations Metabolic pathways Transcription regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood conservation Gene Presence/Absence Comparing genomics data Horizontal comparative genomics Vertical comparative genomics
Phylogenetic distribution(all archaea + all eukaryotes)
Orthologous groups with that distribution:
RNAseL inhibitor
Genomics
Functional associations Metabolic pathways Transcription regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood conservation Gene Presence/Absence Comparing genomics data Horizontal comparative genomics Vertical comparative genomics
Domain composition:
Conserved co-expression:
Genomics
Functional associations Metabolic pathways Transcription regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood conservation Gene Presence/Absence Comparing genomics data Horizontal comparative genomics Vertical comparative genomics
Combined homology and conserved co-expression
A role for the RNase L inhibitor in rRNA processing
predictions directly to experimental groups (Ger Pruijn)
Genomics
Functional associations Metabolic pathways Transcription regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood conservation Gene Presence/Absence Comparing genomics data Horizontal comparative genomics Vertical comparative genomics
The Yeast-2-hybrid techniqueGenomics
Functional associations Metabolic pathways Transcription regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood conservation Gene Presence/Absence Comparing genomics data Horizontal comparative genomics Vertical comparative genomics
Conservation of physical interactions
Overlap between yeast and fly same size as overlap between two different yeast datasets
Genomics
Functional associations Metabolic pathways Transcription regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood conservation Gene Presence/Absence Comparing genomics data Horizontal comparative genomics Vertical comparative genomics
Dataset Comparison
Protein interactions, both proteins in the other dataset
Conserved interactions
Fraction conserved interactions
Average fraction conserved interactions
Ito / UetzYeast vs. Yeast
858 / 697 201 23.4% / 28.8% 26.1%
Ito / GiotYeast vs. Fly
229 / 394 45 19.6% / 11.4% 15.5%
Uetz / GiotYeast vs. Fly
120 / 168 33 27.5% / 19.6% 23.5%
Physical interaction is reasonably well Physical interaction is reasonably well conserved between species (…..compared conserved between species (…..compared to the “conservation” within a species…)to the “conservation” within a species…)
Huynen et al, TIG, 2004
Conservation of protein-protein interaction between Conservation of protein-protein interaction between speciesspecies
Genomics
Functional associations Metabolic pathways Transcription regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood conservation Gene Presence/Absence Comparing genomics data Horizontal comparative genomics Vertical comparative genomics
Conservation of protein-protein interaction Conservation of protein-protein interaction measured by yeast-2-hybrid increases the measured by yeast-2-hybrid increases the likelihood of interactionlikelihood of interaction
Comparison of Giot (Fly) and Ito (Yeast), Uetz (Yeast) y-2-h interactionsComparison of Giot (Fly) and Ito (Yeast), Uetz (Yeast) y-2-h interactions
Genomics
Functional associations Metabolic pathways Transcription regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood conservation Gene Presence/Absence Comparing genomics data Horizontal comparative genomics Vertical comparative genomics
GTPase XAB1/CG3704 hypothetical, GTPase YOR262/CG10222
XAB1 interacts with the DNA repair protein XPA1, XAB1 interacts with the DNA repair protein XPA1, inferred to be required for XPA1’s import in the nucleusinferred to be required for XPA1’s import in the nucleus..
A “new”, conserved interaction:
Fraction hypothetical proteins in conserved Y2H Fraction hypothetical proteins in conserved Y2H interactions relatively lowinteractions relatively low
Hypotheticals:Hypotheticals:In conserved interactionsIn conserved interactions 1313 5% 5% In complete genomeIn complete genome ~1600~1600 27%27%
Genomics
Functional associations Metabolic pathways Transcription regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood conservation Gene Presence/Absence Comparing genomics data Horizontal comparative genomics Vertical comparative genomics
Two types of comparative genomics
Horizontal comparative genomics (HGT) Comparing orthologs Comparing genomics data between
species Vertical comparative genomics
Comparing genomics data within the same species
Integration of scores Bayesian methods
Genomics
Functional associations Metabolic pathways Transcription regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood conservation Gene Presence/Absence Comparing genomics data Horizontal comparative genomics Vertical comparative genomics
Accuracy
Co
ver
age
purifiedcomplexes
TAP
yeast two-hybrid
two methods
three methods
PurifiedComplexesHMS-PCI
combinedevidence
mRNAco-expression
genomic context
syntheticlethality
fra
cti
on
of
refe
ren
ce
se
t c
ov
ere
d b
y d
ata
fraction of data confirmed by reference set
filtered data
raw data
parameter choices
Performance of genomic context compared Performance of genomic context compared to high-throughput interaction datato high-throughput interaction data
Genomics
Functional associations Metabolic pathways Transcription regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood conservation Gene Presence/Absence Comparing genomics data Horizontal comparative genomics Vertical comparative genomics
Trusted co-regulated gene pairs have Trusted co-regulated gene pairs have similar functionssimilar functions
Correlation of co-regulation with functional interactions
Data set of gene pairs Percent same pathway
Number of gene pairs
r > 0.5 43 169,768 r > 0.6 52 65,430 r > 0.7 51 22,459 Sharing 1 TFBS 50 356,947 Sharing 2 TFBS 77 39,818 Sharing 1 TFBS and r > 0.3 86 19,386 Sharing 1 TFBS and r > 0.4 88 11,434 Sharing 1 TFBS and r > 0.5 90 6,687 Sharing 1 TFBS and r > 0.6 90 3,382 Sharing 1 TFBS and r > 0.7 86 1,156
Genomics
Functional associations Metabolic pathways Transcription regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood conservation Gene Presence/Absence Comparing genomics data Horizontal comparative genomics Vertical comparative genomics
Conservation between different datasets: the Bayesian approach
overlap
Co-expressedmRNA 1
Co-expressedmRNA 2
Set 1 Set 2
- -
- +
+ -
+ +
Threshold > sets of ‘interactions’ of gene pairs Interactions present in
all datasets Interactions present in
specific combinations of datasets
Genomics
Functional associations Metabolic pathways Transcription regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood conservation Gene Presence/Absence Comparing genomics data Horizontal comparative genomics Vertical comparative genomics
Conservation between different datasets: the Bayesian approach
Red circles
Historical:
+ ? ? ?
+ + ? ?
+ + + ?
+ + + +Blue diamonds
Consistent:
+ - - -
+ + - -
+ + + -
+ + + +
Genomics
Functional associations Metabolic pathways Transcription regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood conservation Gene Presence/Absence Comparing genomics data Horizontal comparative genomics Vertical comparative genomics
Function prediction in P. falciparum PFI0895c
homologous to subunit 5 of translation elongation factor 3 (elF-3 epsilon), which interacts with the ribosome.
correlated expression with ribosomal proteins L27, L21e and Sa.
Annotation of PFI0895c as elF-3 epsilon most likely. PFI0555c
Co-expressed with two proteins that are involved in protein degradation
the aspartic proteinase and drug target PF14_0075 (plasmepsin IV) and
the ornithine aminotransferase MAL6P1.91 role for PFI0555c in protein degradation. Protein degradation important for host-parasite interaction.
Genomics
Functional associations Metabolic pathways Transcription regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood conservation Gene Presence/Absence Comparing genomics data Horizontal comparative genomics Vertical comparative genomics
Summary
Wealth of data to be explored Genomes Genomics data Comparisons within and between
species Study of evolution Prediction of gene functions
Genomics
Functional associations Metabolic pathways Transcription regulation Signaling pathways Protein complexes Cellular processes
Comparative genomics Comparing genomes Gene Fusions Gene Neighborhood conservation Gene Presence/Absence Comparing genomics data Horizontal comparative genomics Vertical comparative genomics