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Parameter Estimation in Systems Biology

Benchmarking parameter estimation and reverse engineering strategies

author: Pedro Mendes, Virginia Bioinformatics Institute, Virginia Tech

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

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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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