719 research outputs found
Marker and source-marker reprogramming of Most Permissive Boolean networks and ensembles with BoNesis
Boolean networks (BNs) are discrete dynamical systems with applications to
the modeling of cellular behaviors. In this paper, we demonstrate how the
software BoNesis can be employed to exhaustively identify combinations of
perturbations which enforce properties on their fixed points and attractors. We
consider marker properties, which specify that some components are fixed to a
specific value. We study 4 variants of the marker reprogramming problem: the
reprogramming of fixed points, of minimal trap spaces, and of fixed points and
minimal trap spaces reachable from a given initial configuration with the most
permissive update mode. The perturbations consist of fixing a set of components
to a fixed value. They can destroy and create new attractors. In each case, we
give an upper bound on their theoretical computational complexity, and give an
implementation of the resolution using the BoNesis Python framework. Finally,
we lift the reprogramming problems to ensembles of BNs, as supported by
BoNesis, bringing insight on possible and universal reprogramming strategies.
This paper can be executed and modified interactively.Comment: Notebook available at
https://nbviewer.org/github/bnediction/reprogramming-with-bonesis/blob/release/paper.ipyn
Cell fate reprogramming by control of intracellular network dynamics
Identifying control strategies for biological networks is paramount for
practical applications that involve reprogramming a cell's fate, such as
disease therapeutics and stem cell reprogramming. Here we develop a novel
network control framework that integrates the structural and functional
information available for intracellular networks to predict control targets.
Formulated in a logical dynamic scheme, our approach drives any initial state
to the target state with 100% effectiveness and needs to be applied only
transiently for the network to reach and stay in the desired state. We
illustrate our method's potential to find intervention targets for cancer
treatment and cell differentiation by applying it to a leukemia signaling
network and to the network controlling the differentiation of helper T cells.
We find that the predicted control targets are effective in a broad dynamic
framework. Moreover, several of the predicted interventions are supported by
experiments.Comment: 61 pages (main text, 15 pages; supporting information, 46 pages) and
12 figures (main text, 6 figures; supporting information, 6 figures). In
revie
Intelligent systems engineering with reconfigurable computing
Intelligent computing systems comprising microprocessor cores, memory and reconfigurable user-programmable logic represent a promising technology which is well-suited for applications such as digital signal and image processing, cryptography and encryption, etc. These applications employ frequently recursive algorithms which are particularly appropriate when the underlying problem is defined in recursive terms and it is difficult to reformulate it as an iterative procedure. It is known, however, that hardware description languages (such as VHDL) as well as system-level specification languages (such as Handel-C) that are usually employed for specifying the required functionality of reconfigurable systems do not provide a direct support for recursion. In this paper a method allowing recursive algorithms to be easily described in Handel-C and implemented in an FPGA (field-programmable gate array) is proposed. The recursive search algorithm for the knapsack problem is considered as an exampleApplications in Artificial Intelligence - Knowledge EngineeringRed de Universidades con Carreras en Informática (RedUNCI
Identification of control targets in Boolean molecular network models via computational algebra
Motivation: Many problems in biomedicine and other areas of the life sciences
can be characterized as control problems, with the goal of finding strategies
to change a disease or otherwise undesirable state of a biological system into
another, more desirable, state through an intervention, such as a drug or other
therapeutic treatment. The identification of such strategies is typically based
on a mathematical model of the process to be altered through targeted control
inputs. This paper focuses on processes at the molecular level that determine
the state of an individual cell, involving signaling or gene regulation. The
mathematical model type considered is that of Boolean networks. The potential
control targets can be represented by a set of nodes and edges that can be
manipulated to produce a desired effect on the system. Experimentally, node
manipulation requires technology to completely repress or fully activate a
particular gene product while edge manipulations only require a drug that
inactivates the interaction between two gene products. Results: This paper
presents a method for the identification of potential intervention targets in
Boolean molecular network models using algebraic techniques. The approach
exploits an algebraic representation of Boolean networks to encode the control
candidates in the network wiring diagram as the solutions of a system of
polynomials equations, and then uses computational algebra techniques to find
such controllers. The control methods in this paper are validated through the
identification of combinatorial interventions in the signaling pathways of
previously reported control targets in two well studied systems, a p53-mdm2
network and a blood T cell lymphocyte granular leukemia survival signaling
network.Comment: 12 pages, 4 figures, 2 table
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