Biological Integration of Spatial and Temporal Localization of
genes in C. ElegansCesar A. Hidalgo R.
CCNR University of Notre Dame & CCSB, DFCI, Harvard University
mR
NA
A brief review of genetics
GenePromoter
Transcription Factor
Polymerase
Upstream Downstream
Genes are not always on
The Combination of Genes that are ON and OFF determines the phenotype
Systems Biology
-How are these connected?
-When are they expressed? (Condition)
-When are they expressed? (Time)
-Where are they expressed?
-How do they turn on? (Regulatory Networks)
How does the organism work…?
Who is connected with whom..?
Protein-Protein Interactions
How do they turn on?
Regulatory interactions…? (Positive)
Gene1
Gene2
Polymerase
Polymerase
How do they turn on?
Regulatory interactions…? (Negative)
Gene1
Gene2
Polymerase
Polymerase
What happens when we remove one..?
Knock outs
Gene1 Gene2 Gene3
Any difference….?
What happens when we remove two..?
Genetic Interactions..?
Gene1 Gene2 Gene3
Under which conditions are they expressed?
Microarray
Where are they expressed?
GFP
GenePromoter
Transcription Factor
Polymerase
Upstream Downstream
Gene Encoding GFP
Where is the field at?
• Collecting data and developing methods..?
PPI: Cite… Rual et. Al. Ito. El al. Uetz. et. Al. Steltz et. Al.
RNAi:
Microarray. S. Kim. et. Al.
Where is it going..?
PPI
Co-Expression
Localization
The Localizome
A high throughput way to determine spatio-temporal
expression patterns in c. elegans.
COPAS Biosort-Profiler Union Biometrica
Flu
ores
cenc
e
The Localizome (The Data)Profile Individuals
Sort the PopulationThe Localizome (The Data)
L1 larvae
Adults
crm-1
TIME
LENGTH
The Localizome (The Data)
Build Chronograms
The Localizome (Validation)
Validation (Tissue Specificity)
The Localizome (Data Formating)
Image Filtering (Pixelization and Linear Filtering)
Before FilteringAfter Filtering
The Localizome (Validation)
• Validation (Average Image)
Average Expression | Annotation
Average Expression | All Annotations
The Localizome (Validation)
The Localizome (Analysis)
Correlation
-PCC-
PCC=0.03PCC=0.88
The Localizome (Analysis)
The Localizome (Analysis)
P-Value
Pharynx : 1.4x10-5
Vulva Muscle: 3.1x10-4
Annotations
P-ValueEmbryo: 1.4x10-2
Validating Clusters
What can we use this for…?
Are these expressed in the same place
and time…?
Are all the interactions found with other methods
veridical..?
Protein-Protein Interactions are biological only in certain regions
Regulatory Networks
Promoter
TF
TF
Pharynx
The Big Picture
EmbryoAdult
Summary
• Reliable localization data can be produced in a high throughput with the profiler technology.
• This data can be used potentially to identify the sub-networks involved in different organs and in different developmental stages.
• So far we see that the overlap between interacting partners tends to be partial.
Acknowledgments
Alternative Metrics
Overlap Between Significant
Expression Areas
Same Story
Nerve Ring
Pvalue = 3x10-3
When genes come to stage
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