Tag: Boolean networks

Criticality in Biochemical Networks

J Royal Society Interface

Researchers from our center, in collaboration with State University of New York, Binghamton University and the Instituto Gulbenkian de Ciência developed a mathematical and computational framework to understand how biochemical networks contribute to the evolvability, robustness, and resilience of biological organisms.

In a paper in the journal Journal of the Royal Society InterfaceLuis Rocha, George J. Klir Professor of Systems Science, and Drs. Manuel Marques-Pita and Santosh Manicka (who earned his Ph.D. in complex networks and systems from the Luddy School), show that a large amount of redundancy exists in how genes, proteins and other biochemical components process signals. This results in much robustness to perturbations, allowing biological systems to exist in a stable or near-critical dynamical regime, despite being composed of thousands of biochemical variables which would ordinarily result in chaotic dynamics.

The measure of effective connectivity developed by Rocha and Marques-Pita captures redundancy in automata networks and is shown in the paper to be highly predictive of dynamical regime of biochemical systems ranging from flower development to breast cancer in humans. The approach thus adds empirical validity to several  well-known hypotheses in theoretical biology: 1) that canalization adds robustness to biological development put forth by C.H. Waddington, 2) that redundancy is essential for evolvability put forth by Michael Conrad, and 3) that biological organisms exist in a near-critical dynamical regime put forth by Stuart Kauffman. The new work further connects the three hypotheses by equating canalization with redundancy, providing a  measure of effective connectivity based on dynamical redundancy, and further showing that this measure very accurately predicts the dynamical regime of biochemical networks.

You can read the article following the links in reference:

Manicka Santosh, Marques-Pita Manuel and Rocha Luis M. [2022]. “Effective connectivity determines the critical dynamics of biochemical continue reading.

Uncovering the “master switches” of biochemical networks can explain the effects of drugs in the destruction of cancer cells

Researchers from our lab, in collaboration with the Luddy School of Informatics, Computing, and Engineering, the Instituto Gulbenkian de Ciência, and Northeastern University have developed a mathematical framework that increases our ability to explain and control biochemical systems, including those involved in disease.

In a paper featured on the cover of the journal Proceedings of the National Academy of Sciences (PNAS), Professor of Informatics Luis Rocha and Alexander Gates (who earned his Ph.D. in complex networks and systems from the Luddy School), introduce an effective graph that can capture nonlinear logical redundancy present in biochemical network regulation, signaling, and control.

Rion Correia (a member of the CSBC lab, who also earned his Ph.D. in complex networks and systems from the Luddy School and Xuan Wang, a current Ph.D. candidate, and member of the lab) are also working on the project. Together, the authors demonstrate the utility of the approach with computational models of human cancer cells, showing that the effective graph reveals why some cancer medications are more effective than others in killing breast cancer cells.

You can read the full details via the press releases below:

Luddy Press Release

Instituto Gulbenkian de Ciência Press Release

You can read the article here:

https://www.pnas.org/content/118/12/e2022598118

*Those interested in contacting the authors should do so directly, via the links provided above.… continue reading.

New Ph.D. Graduate

Congratulations to Alexander Gates for successfully defending his dissertation entitled “The anatomical and effective structure of complex systems” on April 3rd 2017, co-supervised by Randy beer and Luis Rocha. Alex completed a dual-PhD degree in the Complex Systems track of the Informatics PhD Program as well as the Cognitive Science program at Indiana University. Alex has accepted a postdoctoral position at Northeastern University at the Center for Complex Network Research. … continue reading.

Art-Science Installation Musical Morphogenesis

Musical Morphogenesis’ is an interactive installation that translates to sound, movement and lights the dynamics behind the development of petals in a flower. It is a collaborative piece developed by designers, architects, musicians and scientists in Luis Rocha‘s CASCI group. The control of this robotic “macroscope” is an implementation of the gene regulatory network of the Thaliana Arabidopsis flower. The installation provides a sensorial exploration of the dynamics between genes and proteins that leads to organ formation in plants, namely sepals, stamen, and petals. The genetic network provides an interactive “genetic soundtrack” that allows visitors to control the development of the plant towards its wild-type or mutant states. The installation has been on display at various museums such as the Science Museum in Lisbon, Gulbenkian Foundation, and the Belém ArtFest. This week it will be displayed at Dia D Ligações – Gulbenkian Foundation.… continue reading.

Control of Complex Networks

Network science has allowed us to understand the organization of complex systems across disciplines. However, there is a need to understand how to control them; for example, to identify strategies to revert a diseased cell to a healthy state in cancer treatment. Recent work in the field—based on linear control theory—suggests that the controllability of complex systems can be predicted solely from the graph of interactions between variables, without considering their dynamics. Such graph-based approaches have been used, for instance, to suggest that biological systems are harder to control and have appreciably different control profiles than social or technological systems. The methodology has also been increasingly used in many applications from financial to biochemical networks.

In work published today in Nature Scientific Reports, CNetS graduate student Alexander Gates and Professor Luis Rocha demonstrate that such graph-based methods fail to characterize controllability when dynamics are introduced. The study computed the control profiles of large ensembles of multivariate systems as well as existing Systems Biology models of biochemical regulation in various organisms.… continue reading.