Benchmarking parameter estimation and reverse engineering strategies
Description
Parameter estimation has become a central problem in systems biology, both in the form of calibration of bottom-up models or as a component of reverse engineering algorithms. With a proliferation of algorithms proposed for these purposes it has become important to compare them in objective ways. I will argue that in silico biochemical network models are extremely useful for this purpose. Several networks will be presented that are challenging tests for parameter estimation and network inference. An issue that arises from the use of in silico networks, though, is whether they can provide realistic data. The application of this benchmarking methodology will be illustrated with a comparison of four reverse engineering methods.
Joint work with Diogo Camacho, Paola Vera Licona, and Reinhard Laubenbacher
Categories
Top: Computer Science: BioinformaticsTop: Computer Science: Machine Learning: Statistical Learning
| Slides | |
| 0:00 | Benchmarking parameter estimation and reverse engineering strategies |
| 1:31 | pasi |
| 2:18 | Original paper |
| 2:43 | Parameter estimation |
| 4:43 | Optimization methods |
| 6:30 | 3-step pathway with gene expression |
| 7:54 | 3-step model |
| 9:42 | 3-step model – results |
| 12:08 | 3-step model – results |
| 13:06 | Results, 2nd attempt… |
| 15:28 | Issues with parameter estimation |
| 16:36 | Top-down modeling Reverse engineering |
| 17:44 | The DREAM projet |
| 23:13 | In silico biochemical networks for algorithm comparison |
| 24:48 | Biochemical networks |
| 26:41 | Bioinformatics |
| 29:08 | Kinetics of transcription |
| 29:19 | Kinetics for AGN |
| 30:17 | Adding noise to simulated data |
| 31:11 | Evaluation of Statistical Methods in Microarray Differential Expression Analysis |
| 32:00 | Comparison: false positives |
| 32:16 | Comparison: false negatives |
| 33:20 | Effect of kinetics |
| 33:33 | CoopSF41 |
| 33:42 | CoopSF41: |
| 34:22 | Metrics |
| 35:57 | How about the rest of biochemistry ? |
| 36:11 | The Claytor Network |
| 37:02 | Protein synthesis and signaling |
| 37:12 | Protein synthesis and signaling |
| 37:54 | Genetic regulation |
| 38:06 | Gene knock-out experiments |
| 38:38 | Gene knock-out experiments |
| 38:46 | Gene knock-out experiments |
| 38:51 | Gene knock-out experiments |
| 38:53 | Comparison of four reverse engineering methods |
| 38:54 | Increasing noise levels |
| 39:11 | ROC curve for effect of noise |
| 39:41 | Heterozygous mutant experiments |
| 39:49 | Acknowledgements |
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