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Practical Inference Methods for Mechanistic Modelling of Biological Systems
Pascal

Gene regulatory network reconstruction by Bayesian integration of prior knowledge and/or different experimental conditions

author: Dirk Husmeier, BioSS - Biomathematics & Statistics Scotland

Description

There have been various attempts to improve the reconstruction of gene regulatory networks from microarray data by the systematic integration of biological prior knowledge. Our approach follows the Bayesian paradigm where the prior knowledge is expressed in terms of energy functions, from which a prior distribution over network structures is obtained in the form of a Gibbs distribution. The hyperparameters of this distribution represent the weights associated with the prior knowledge relative to the data. We have derived and tested an MCMC scheme for sampling networks and hyperparameters simultaneously from the posterior distribution, thereby automatically learning how to trade off information from the prior and the data. We have extended this approach to a Bayesian coupling scheme for learning gene regulatory networks from a combination of related data sets that were obtained under different experimental conditions and are therefore potentially associated with different active subpathways.

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Slides
0:00 Statistical Applications in Genetics and Molecular Biology
0:10 Systems Biology - 1
0:18 Systems Biology - 2
0:24 Systems Biology - 3
0:27 Systems Biology - 4
0:31 Systems Biology - 5
0:38 Systems Biology - 6
0:42 Problem - 1
0:55 Problem - 2
1:02 Systematically Integrating Different Sources - 1
1:12 Systematically Integrating Different Sources - 2
1:20 Systematically Integrating Different Sources - 3
1:23 Systematically Integrating Different Sources - 4
1:47 Which Sources of Prior Knowledge Are Reliable?
1:55 Overview of the Talk
2:04 - Revision: Bayesian Networks
2:07 Bayesian Networks - 1
2:59 Bayesian Networks - 2
4:58 Bayesian Networks Versus Causal Networks - 1
5:20 Bayesian Networks Versus Causal Networks - 2
5:45 Symmetry Breaking
6:29 P(D|M)
6:35 P(M)
6:43 P(M|D) ~ P(D|M) P(M)
6:55 Learning Bayesian Networks - 1
7:42 Learning Bayesian Networks - 2
7:59 Learning Bayesian Networks - 3
8:04 Learning Bayesian Networks - 2
8:16 - Integration of Prior Knowledge
8:19 Estimating Gene Networks
8:34 Use TF Binding Motifs in Promoter Sequences
9:12 Biological Prior Knowledge - 1
9:49 Biological Prior Knowledge - 2
10:21 Notation
10:36 Energy of a Network - 1
10:39 Biological Prior Knowledge - 2
10:41 Energy of a Network - 1
11:49 Sample Networks and Hyperparameters from the Posterior Distribution - 1
12:08 Energy of a Network - 2
12:54 Energy of a Network - 3
13:47 Approximation of the Partition Function - 1
14:31 - Questions
14:47 - Questions
15:44 Multiple Sources of Prior Knowledge
16:10 Energy of a Network - 4
16:26 Approximation of the Partition Function - 2
16:42 MCMC Sampling Scheme
16:43 - Questions
17:01 MCMC Sampling Scheme
17:03 Sample Networks and Hyperparameters from the Posterior Distribution
17:51 Metropolis-Hastings Scheme - 1
18:01 Metropolis-Hastings Scheme - 2
18:28 MCMC with One Prior - 1
18:38 MCMC with One Prior - 2
19:03 MCMC with One Prior - 3
19:13 MCMC with One Prior - 4
19:20 MCMC with One Prior - 5
19:26 Approximation of the Partition Function - 3
19:30 MCMC with Two Priors
19:33 Bayesian Networks with Biological Prior Knowledge
19:40 Bayesian Networks with Two Sources of Prior - 1
20:08 Bayesian Networks with Two Sources of Prior - 2
20:15 Bayesian Networks with Two Sources of Prior - 3
20:18 - Empirical Evaluation
20:21 Evaluation - 1
20:47 Application to the Raf Regulatory Network
20:49 Raf Regulatory Network - 1
21:12 Raf Regulatory Network - 2
21:13 Evaluation: Raf Signalling Pathway
21:15 Data: Prior Knowledge - 1
21:16 Flow Cytometry Data
22:07 Microarray Example
22:48 Data: Prior Knowledge - 2
22:48 Flow Cytometry Data and KEGG
23:03 Prior Knowledge from KEGG
23:07 Prior Distributor
23:17 Prior Knowledge from KEGG
23:25 Prior Distributor
23:28 Prior Knowledge from KEGG
23:32 Prior Distributor
23:36 Prior Knowledge from KEGG
23:37 Prior Distributor
23:58 The Data and the Priors
24:15 Evaluation - 2
24:18 Bayesian Networks with Two Sources of Prior - 4
24:25 Bayesian Networks with Two Sources of Prior - 5
24:28 Sampled Values of the Hyperparameters
25:02 How to Compare the Recovered Networks?
25:16 Deterministic Interference
25:42 Probabilistic Interference
25:47 Tresholding
25:52 Performance Evaluation: ROC Curves - 1
26:11 Performance Evaluation: ROC Curves - 2
26:34 Alternative Performance Evaluation: True Positive (TP) Scores - 1
26:41 Alternative Performance Evaluation: True Positive (TP) Scores - 2
26:56 Directed Graph Evaluation - DGE
27:08 Undirected Graph Evaluation - UGE
27:14 Evaluation - 3
27:24 Flow Cytometry Data and KEGG
29:31 Evaluation - 4
29:35 Learning the Trade-Off Hyperparameter
30:04 Flow Cytometry Data and KEGG
30:12 Learning the Trade-Off Hyperparameter
30:23 Flow Cytometry Data and KEGG
30:28 Learning the Trade-Off Hyperparameter
31:33 Learning the Trade-Off Hyperparameters on Simulated Data
31:48 New Evidence for the Accepted Network
32:33 Reconstructing Regulatory Networks under Different Experimental Conditions
32:38 The Original Problem of Reconstructing - 1
32:45 The Original Problem of Reconstructing - 2
32:46 Multiple Data Sets Obtained under Different Experimental Conditions - 1
32:47 Multiple Data Sets Obtained under Different Experimental Conditions - 2
33:07 Multiple Data Sets Obtained under Different Experimental Conditions - 3
33:33 Multiple Data Sets Obtained under Different Experimental Conditions - 4
33:38 Multiple Data Sets Obtained under Different Experimental Conditions - 5
33:42 Combining the Data
33:43 Combining the Data - 1
33:52 Multiple Data Sets Obtained under Different Experimental Conditions - 5
33:55 Combining the Data - 1
34:14 Combining the Data - 2
34:15 Compromise - 1
35:28 Compromise - 2
35:34 Compromise - 3
35:39 Compromise - 4
35:51 Compromise - 5
35:56 Compromise - 6
35:58 MCMC
36:09 Empirical Evaluation
36:13 Simulated Data - 1
36:13 Simulated Data - 2
36:19 Simulated Data - 3
36:28 Simulated Data - 4
36:31 Simulated Data - 5
36:33 Data
36:40 Sampling the Hyperparameters
36:45 Can We Detect the Corrupt (Noisy) Data Set? - 1
36:51 Can We Detect the Corrupt (Noisy) Data Set? - 2
36:53 Can We Detect the Corrupt (Noisy) Data Set? - 3
37:42 Evaluation - 5
37:50 Simulated Data - 6
38:01 Cytometry Data
38:21 Convergence Assessment
38:59 Acceptance Ratios

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Reviews and comments:

Comment1 fadl, April 11, 2008 at 9:31 a.m.:

we can't follow his talk without the presentation.


Comment2 Bipin Singh, September 10, 2008 at 6:30 p.m.:

wonderful tutorial on gene regulatory networks i have ever seen.I expect you will provide video tutorial on other bioinformatics related topic in future.


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