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Biological Integration of Spatial and Temporal Localization of genes in C. Elegans

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

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Biological Integration of Spatial and Temporal Localization of genes in C. Elegans

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  1. 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

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

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

  4. Systems Biology How does the organism work…? • 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)

  5. Who is connected with whom..? Protein-Protein Interactions

  6. Polymerase Polymerase How do they turn on? Regulatory interactions…? (Positive) Gene1 Gene2

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

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

  9. Gene1 Gene2 What happens when we remove two..? Genetic Interactions..? Gene3

  10. Under which conditions are they expressed? Microarray

  11. Polymerase Transcription Factor Gene Gene Encoding GFP Promoter Where are they expressed? GFP Upstream Downstream

  12. 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….

  13. PPI Co-Expression Localization Where is it going..?

  14. The Localizome A high throughput way to determine spatio-temporal expression patterns in c. elegans.

  15. The Localizome (The Data) COPAS Biosort-ProfilerUnion Biometrica Profile Individuals Fluorescence

  16. The Localizome (The Data) Sort the Population

  17. L1 larvae crm-1 Adults The Localizome (The Data) Build Chronograms TIME LENGTH

  18. The Localizome (Validation) Validation (Tissue Specificity)

  19. The Localizome (Data Formating) Image Filtering (Pixelization and Linear Filtering) Before Filtering After Filtering

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

  21. The Localizome (Validation)

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

  23. The Localizome (Analysis)

  24. Annotations P-Value Embryo: 1.4x10-2 The Localizome (Analysis) P-Value Pharynx : 1.4x10-5 Vulva Muscle: 3.1x10-4

  25. Validating Clusters

  26. What can we use this for…? Are all the interactions found with other methods veridical..? Are these expressed in the same place and time…?

  27. Protein-Protein Interactions are biological only in certain regions

  28. Regulatory Networks TF Promoter TF

  29. Pharynx Embryo Adult The Big Picture

  30. 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.

  31. Acknowledgments

  32. Alternative Metrics Overlap Between Significant Expression Areas

  33. Same Story Nerve Ring Pvalue = 3x10-3

  34. When genes come to stage

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