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Dive into the research topics where Boyan Yordanov is active.

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Featured researches published by Boyan Yordanov.


Science | 2014

Defining an essential transcription factor program for naïve pluripotency

Sara-Jane Dunn; Graziano Martello; Boyan Yordanov; Stephen Emmott; Austin Smith

Predicting stem cell renewal or differentiation Predicting complex mammalian cell behavior is extremely challenging. Dunn et al. developed a computational model that predicts when embryonic stem cells will self-renew or differentiate. The model revealed an essential program governing pluripotency and identifies a minimal set of components and interactions that accurately predict responses to genetic perturbation. Science, this issue p. 1156 Iterative experimental and computational analysis reveals a simple molecular program for embryonic stem cell self-renewal. The gene regulatory circuitry through which pluripotent embryonic stem (ES) cells choose between self-renewal and differentiation appears vast and has yet to be distilled into an executive molecular program. We developed a data-constrained, computational approach to reduce complexity and to derive a set of functionally validated components and interaction combinations sufficient to explain observed ES cell behavior. This minimal set, the simplest version of which comprises only 16 interactions, 12 components, and three inputs, satisfies all prior specifications for self-renewal and furthermore predicts unknown and nonintuitive responses to compound genetic perturbations with an overall accuracy of 70%. We propose that propagation of ES cell identity is not determined by a vast interactome but rather can be explained by a relatively simple process of molecular computation.


chinese control conference | 2012

Temporal Logic Control of Discrete-Time Piecewise Affine Systems

Boyan Yordanov; Jana Tumova; Ivana Černá; Jiří Barnat; Calin Belta

We present a computational framework for automatic synthesis of a feedback control strategy for a discrete-time piecewise affine (PWA) system from a specification given as a linear temporal logic (LTL) formula over an arbitrary set of linear predicates in the systems state variables. Our approach consists of two main steps. First, by defining appropriate partitions for its state and input spaces, we construct a finite abstraction of the PWA system in the form of a control transition system. Second, by leveraging ideas and techniques from LTL model checking and Rabin games, we develop an algorithm to generate a control strategy for the finite abstraction. While provably correct and robust to state measurements and small perturbations in the applied inputs, the overall procedure is conservative and expensive. The proposed algorithms have been implemented as a software package and made available for download. Illustrative examples are included.


IEEE Transactions on Automatic Control | 2010

Formal Analysis of Discrete-Time Piecewise Affine Systems

Boyan Yordanov; Calin Belta

In this technical note, we study temporal logic properties of trajectories of discrete-time piecewise affine (PWA) systems. Specifically, given a PWA system and a linear temporal logic formula over regions in its state space, we attempt to find the largest region of initial states from which all trajectories of the system satisfy the formula. Our method is based on the iterative computation and model checking of finite quotients. We illustrate our method by analyzing PWA models of two synthetic gene networks.


ACS Synthetic Biology | 2014

Computational design of nucleic acid feedback control circuits.

Boyan Yordanov; Jongmin Kim; Rasmus Lerchedahl Petersen; Angelina Shudy; Vishwesh V. Kulkarni; Andrew Phillips

The design of synthetic circuits for controlling molecular-scale processes is an important goal of synthetic biology, with potential applications in future in vitro and in vivo biotechnology. In this paper, we present a computational approach for designing feedback control circuits constructed from nucleic acids. Our approach relies on an existing methodology for expressing signal processing and control circuits as biomolecular reactions. We first extend the methodology so that circuits can be expressed using just two classes of reactions: catalysis and annihilation. We then propose implementations of these reactions in three distinct classes of nucleic acid circuits, which rely on DNA strand displacement, DNA enzyme and RNA enzyme mechanisms, respectively. We use these implementations to design a Proportional Integral controller, capable of regulating the output of a system according to a given reference signal, and discuss the trade-offs between the different approaches. As a proof of principle, we implement our methodology as an extension to a DNA strand displacement software tool, thus allowing a broad range of nucleic acid circuits to be designed and analyzed within a common modeling framework.


conference on decision and control | 2010

A symbolic approach to controlling piecewise affine systems

Jana Tumova; Boyan Yordanov; Calin Belta; Ivana Černá; Jiri Barnat

We present a computational framework for automatic synthesis of a feedback control strategy for a piecewise affine (PWA) system from a specification given as a Linear Temporal Logic (LTL) formula over an arbitrary set of linear predicates in its state variables. First, by defining partitions for its state and input spaces, we construct a finite abstraction of the PWA system in the form of a control transition system. Second, we develop an algorithm to generate a control strategy for the finite abstraction. While provably correct and robust to small perturbations in both state measurements and applied inputs, the overall procedure is conservative and expensive. The proposed algorithms have been implemented and are available for download. Illustrative examples are included


Molecular Systems Biology | 2016

Orthogonal intercellular signaling for programmed spatial behavior.

Paul Grant; Neil Dalchau; James R. Brown; Fernán Federici; Tim Rudge; Boyan Yordanov; Om Patange; Andrew Phillips; Jim Haseloff

Bidirectional intercellular signaling is an essential feature of multicellular organisms, and the engineering of complex biological systems will require multiple pathways for intercellular signaling with minimal crosstalk. Natural quorum‐sensing systems provide components for cell communication, but their use is often constrained by signal crosstalk. We have established new orthogonal systems for cell–cell communication using acyl homoserine lactone signaling systems. Quantitative measurements in contexts of differing receiver protein expression allowed us to separate different types of crosstalk between 3‐oxo‐C6‐ and 3‐oxo‐C12‐homoserine lactones, cognate receiver proteins, and DNA promoters. Mutating promoter sequences minimized interactions with heterologous receiver proteins. We used experimental data to parameterize a computational model for signal crosstalk and to estimate the effect of receiver protein levels on signal crosstalk. We used this model to predict optimal expression levels for receiver proteins, to create an effective two‐channel cell communication device. Establishment of a novel spatial assay allowed measurement of interactions between geometrically constrained cell populations via these diffusible signals. We built relay devices capable of long‐range signal propagation mediated by cycles of signal induction, communication and response by discrete cell populations. This work demonstrates the ability to systematically reduce crosstalk within intercellular signaling systems and to use these systems to engineer complex spatiotemporal patterning in cell populations.


Automatica | 2013

Formal analysis of piecewise affine systems through formula-guided refinement

Boyan Yordanov; Jana Tmová; Ivana Erná; Jiří Barnat; Calin Belta

We present a computational framework for identifying a set of initial states from which all trajectories of a piecewise affine (PWA) system with additive uncertainty satisfy a linear temporal logic (LTL) formula over a set of linear predicates in its state variables. Our approach is based on the construction and refinement of finite abstractions of infinite systems. We derive conditions guaranteeing the equivalence of an infinite system and its finite abstraction with respect to a specific LTL formula and propose a method for the construction of such formula-equivalent abstractions. While provably correct, the overall method is conservative and expensive. A tool for PWA systems implementing the proposed procedure using polyhedral operations and analysis of finite graphs is made available. Examples illustrating the analysis of PWA models of gene networks are included.


ACS Synthetic Biology | 2014

A Computational Method for Automated Characterization of Genetic Components

Boyan Yordanov; Neil Dalchau; Paul Grant; Michael Pedersen; Stephen Emmott; Jim Haseloff; Andrew Phillips

The ability to design and construct synthetic biological systems with predictable behavior could enable significant advances in medical treatment, agricultural sustainability, and bioenergy production. However, to reach a stage where such systems can be reliably designed from biological components, integrated experimental and computational techniques that enable robust component characterization are needed. In this paper we present a computational method for the automated characterization of genetic components. Our method exploits a recently developed multichannel experimental protocol and integrates bacterial growth modeling, Bayesian parameter estimation, and model selection, together with data processing steps that are amenable to automation. We implement the method within the Genetic Engineering of Cells modeling and design environment, which enables both characterization and design to be integrated within a common software framework. To demonstrate the application of the method, we quantitatively characterize a synthetic receiver device that responds to the 3-oxohexanoyl-homoserine lactone signal, across a range of experimental conditions.


nasa formal methods symposium | 2013

SMT-Based Analysis of Biological Computation

Boyan Yordanov; Christoph M. Wintersteiger; Youssef Hamadi; Hillel Kugler

Synthetic biology focuses on the re-engineering of living organisms for useful purposes while DNA computing targets the construction of therapeutics and computational circuits directly from DNA strands. The complexity of biological systems is a major engineering challenge and their modeling relies on a number of diverse formalisms. Moreover, many applications are “mission-critical” (e.g. as recognized by NASA’s Synthetic Biology Initiative) and require robustness which is difficult to obtain. The ability to formally specify desired behavior and perform automated computational analysis of system models can help address these challenges, but today there are no unifying scalable analysis frameworks capable of dealing with this complexity.


international workshop on hybrid systems computation and control | 2008

Parameter Synthesis for Piecewise Affine Systems from Temporal Logic Specifications

Boyan Yordanov; Calin Belta

In this paper, we consider discrete-time continuous-space Piecewise Affine (PWA) systems with parameter uncertainties, and study temporal logic properties of their trajectories. Specifically, given a PWA system with polytopal parameter uncertainties, and a Linear Temporal Logic (LTL) formula over linear predicates in the states of the system, we attempt to find subsets of parameters guaranteeing the satisfaction of the formula by all trajectories of the system. We illustrate our method by applying it to a PWA model of a two-gene network.

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Ebru Aydin Gol

Middle East Technical University

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