Exact Probability Landscapes of Stochastic Phenotype Switching in Feed-Forward Loops: Phase Diagrams of Multimodality

Feed-forward loops (FFLs) are among the most ubiquitously found motifs of reaction networks in nature. However, little is known about their stochastic behavior and the variety of network phenotypes they can exhibit. In this study, we provide full characterizations of the properties of stochastic multimodality of FFLs, and how switching between different network phenotypes are controlled. We have computed the exact steady-state probability landscapes of all eight types of coherent and incoherent FFLs using the finite-butter Accurate Chemical Master Equation (ACME) algorithm, and quantified the exact topological features of their high-dimensional probability landscapes using persistent homology. Through analysis of the degree of multimodality for each of a set of 10,812 probability landscapes, where each landscape resides over 105–106 microstates, we have constructed comprehensive phase diagrams of all relevant behavior of FFL multimodality over broad ranges of input and regulation intensities, as well as different regimes of promoter binding dynamics. In addition, we have quantified the topological sensitivity of the multimodality of the landscapes to regulation intensities. Our results show that with slow binding and unbinding dynamics of transcription factor to promoter, FFLs exhibit strong stochastic behavior that is very different from what would be inferred from deterministic models. In addition, input intensity play major roles in the phenotypes of FFLs: At weak input intensity, FFL exhibit monomodality, but strong input intensity may result in up to 6 stable phenotypes. Furthermore, we found that gene duplication can enlarge stable regions of specific multimodalities and enrich the phenotypic diversity of FFL networks, providing means for cells toward better adaptation to changing environment. Our results are directly applicable to analysis of behavior of FFLs in biological processes such as stem cell differentiation and for design of synthetic networks when certain phenotypic behavior is desired.

Download Full-text

Correlating In silico Feed-forward Loop Knockout Experiments with the Topological Features of Transcriptional Regulatory Networks

Proceedings of the 8th International Conference on Bio-inspired Information and Communications Technologies (formerly BIONETICS) ◽

10.4108/icst.bict.2014.257916 ◽

2015 ◽

Cited By ~ 1

Author(s):

Ahmed Abdelzaher ◽

Michael Mayo ◽

Preetam Ghosh ◽

Edward Perkins

Keyword(s):

In Silico ◽

Regulatory Networks ◽

Transcriptional Regulatory Networks ◽

Feed Forward ◽

Feed Forward Loop ◽

Topological Features ◽

Transcriptional Regulatory

Download Full-text

Construction of a lncRNA-mediated feed-forward loop network reveals global topological features and prognostic motifs in human cancers

Oncotarget ◽

10.18632/oncotarget.10004 ◽

2016 ◽

Vol 7 (29) ◽

pp. 45937-45947 ◽

Cited By ~ 14

Author(s):

Shangwei Ning ◽

Yue Gao ◽

Peng Wang ◽

Xiang Li ◽

Hui Zhi ◽

...

Keyword(s):

Feed Forward ◽

Feed Forward Loop ◽

Human Cancers ◽

Topological Features ◽

Loop Network

Download Full-text

Imaging of platinum-shadowed macromolecular complexes in dark field

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100110891 ◽

1984 ◽

Vol 42 ◽

pp. 146-147

Author(s):

D.W. Andrews ◽

F.P. Ottensmeyer

Keyword(s):

Thin Film ◽

Three Dimensional ◽

Average Diameter ◽

Dark Field ◽

Bright Field ◽

Field Mode ◽

Macromolecular Complexes ◽

Average Mass ◽

Topological Features ◽

Projection Images

Shadowing with heavy metals has been used for many years to enhance the topological features of biological macromolecular complexes. The three dimensional features present in directionaly shadowed specimens often simplifies interpretation of projection images provided by other techniques. One difficulty with the method is the relatively large amount of metal used to achieve sufficient contrast in bright field images. Thick shadow films are undesirable because they decrease resolution due to an increased tendency for microcrystalline aggregates to form, because decoration artefacts become more severe and increased cap thickness makes estimation of dimensions more uncertain.The large increase in contrast provided by the dark field mode of imaging allows the use of shadow replicas with a much lower average mass thickness. To form the images in Fig. 1, latex spheres of 0.087 μ average diameter were unidirectionally shadowed with platinum carbon (Pt-C) and a thin film of carbon was indirectly evaporated on the specimen as a support.

Download Full-text

Transmission electron microscope studies in special ceramics

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100108489 ◽

1978 ◽

Vol 36 (1) ◽

pp. 268-269

Author(s):

A. Zangvil ◽

L.J. Gauckler ◽

G. Schneider ◽

M. Rühle

Keyword(s):

Phase Diagrams ◽

Crystal Structures ◽

Thin Foil ◽

Limited Extent ◽

Complex Materials ◽

X Ray Diffraction ◽

X Ray ◽

Transmission Electron ◽

Electron Microscopes ◽

Lattice Resolution

The use of high temperature special ceramics which are usually complex materials based on oxides, nitrides, carbides and borides of silicon and aluminum, is critically dependent on their thermomechanical and other physical properties. The investigations of the phase diagrams, crystal structures and microstructural features are essential for better understanding of the macro-properties. Phase diagrams and crystal structures have been studied mainly by X-ray diffraction (XRD). Transmission electron microscopy (TEM) has contributed to this field to a very limited extent; it has been used more extensively in the study of microstructure, phase transformations and lattice defects. Often only TEM can give solutions to numerous problems in the above fields, since the various phases exist in extremely fine grains and subgrain structures; single crystals of appreciable size are often not available. Examples with some of our experimental results from two multicomponent systems are presented here. The standard ion thinning technique was used for the preparation of thin foil samples, which were then investigated with JEOL 200A and Siemens ELMISKOP 102 (for the lattice resolution work) electron microscopes.

Download Full-text