Literature DB >> 24511382

Single timepoint models of dynamic systems.

K Sachs1, S Itani2, J Fitzgerald3, B Schoeberl3, G P Nolan1, C J Tomlin2.   

Abstract

Many interesting studies aimed at elucidating the connectivity structure of biomolecular pathways make use of abundance measurements, and employ statistical and information theoretic approaches to assess connectivities. These studies often do not address the effects of the dynamics of the underlying biological system, yet dynamics give rise to impactful issues such as timepoint selection and its effect on structure recovery. In this work, we study conditions for reliable retrieval of the connectivity structure of a dynamic system, and the impact of dynamics on structure-learning efforts. We encounter an unexpected problem not previously described in elucidating connectivity structure from dynamic systems, show how this confounds structure learning of the system and discuss possible approaches to overcome the confounding effect. Finally, we test our hypotheses on an accurate dynamic model of the IGF signalling pathway. We use two structure-learning methods at four time points to contrast the performance and robustness of those methods in terms of recovering correct connectivity.

Keywords:  Bayesian networks; networks; perturbations; signalling; structure learning

Year:  2013        PMID: 24511382      PMCID: PMC3915837          DOI: 10.1098/rsfs.2013.0019

Source DB:  PubMed          Journal:  Interface Focus        ISSN: 2042-8898            Impact factor:   3.906


  16 in total

1.  Using graphical models and genomic expression data to statistically validate models of genetic regulatory networks.

Authors:  A J Hartemink; D K Gifford; T S Jaakkola; R A Young
Journal:  Pac Symp Biocomput       Date:  2001

2.  Mutual information relevance networks: functional genomic clustering using pairwise entropy measurements.

Authors:  A J Butte; I S Kohane
Journal:  Pac Symp Biocomput       Date:  2000

3.  A role for IGF-1R-targeted therapies in small-cell lung cancer?

Authors:  Kathy Gately; Ian Collins; Lydia Forde; Bassel Al-Alao; Vincent Young; Michael Gerg; Friedrich Feuerhake; Kenneth O'Byrne
Journal:  Clin Lung Cancer       Date:  2011-01       Impact factor: 4.785

Review 4.  Targeted therapies for adrenocortical carcinoma: IGF and beyond.

Authors:  Michael J Demeure; Kimberly J Bussey; Lawrence S Kirschner
Journal:  Horm Cancer       Date:  2011-12       Impact factor: 3.869

5.  Multivariate dependence and genetic networks inference.

Authors:  A A Margolin; K Wang; A Califano; I Nemenman
Journal:  IET Syst Biol       Date:  2010-11       Impact factor: 1.615

6.  Causal protein-signaling networks derived from multiparameter single-cell data.

Authors:  Karen Sachs; Omar Perez; Dana Pe'er; Douglas A Lauffenburger; Garry P Nolan
Journal:  Science       Date:  2005-04-22       Impact factor: 47.728

7.  Learning signaling network structures with sparsely distributed data.

Authors:  Karen Sachs; Solomon Itani; Jennifer Carlisle; Garry P Nolan; Dana Pe'er; Douglas A Lauffenburger
Journal:  J Comput Biol       Date:  2009-02       Impact factor: 1.479

8.  Characterization of patient specific signaling via augmentation of Bayesian networks with disease and patient state nodes.

Authors:  Karen Sachs; Andrew J Gentles; Ryan Youland; Solomon Itani; Jonathan Irish; Garry P Nolan; Sylvia K Plevritis
Journal:  Conf Proc IEEE Eng Med Biol Soc       Date:  2009

9.  Bayesian network approach to cell signaling pathway modeling.

Authors:  Karen Sachs; David Gifford; Tommi Jaakkola; Peter Sorger; Douglas A Lauffenburger
Journal:  Sci STKE       Date:  2002-09-03

10.  Learning cyclic signaling pathway structures while minimizing data requirements.

Authors:  K Sachs; S Itani; J Fitzgerald; L Wille; B Schoeberl; M A Dahleh; G P Nolan
Journal:  Pac Symp Biocomput       Date:  2009
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