Biological Integration of Spatial and Temporal Localization of genes in C. Elegans Cesar A. Hidalgo R. CCNR University of Notre Dame & CCSB, DFCI, Harvard.

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Presentation transcript:

Biological Integration of Spatial and Temporal Localization of genes in C. Elegans Cesar A. Hidalgo R. CCNR University of Notre Dame & CCSB, DFCI, Harvard University

mRNA A brief review of genetics Gene Promoter Transcription Factor Polymerase Upstream Downstream Genes are not always on

The Combination of Genes that are ON and OFF determines the phenotype

Systems Biology RNAi MicroArray GFP-Localization PPI Genetic Interactions Regulatory Networks -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

How do they turn on? Regulatory interactions…? (Negative) Gene1 Gene2 Polymerase

What happens when we remove one..? RNAi MicroArray GFP-Localization PPI Genetic Interactions Regulatory Networks Knock outs Gene1 Gene2 Gene3 Any difference….?

What happens when we remove two..? Genetic Interactions..? Gene1Gene2 Gene3

Under which conditions are they expressed? Microarray

Where are they expressed? GFP Gene Promoter 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. Coverage is still very low compared to what is expected to be out there….

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 Fluorescence The Localizome (The Data) Profile Individuals

Sort the Population The 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 Filtering After Filtering

The Localizome (Validation) Validation (Average Image) Average Expression | Annotation Average Expression | All Annotations

The Localizome (Validation)

The Localizome (Analysis) Correlation -PCC- PCC=0.03 PCC=0.88

The Localizome (Analysis)

P-Value Pharynx : 1.4x10 -5 Vulva Muscle: 3.1x10 -4 Annotations P-Value Embryo: 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

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