ayush pandey - Academia.edu (original) (raw)
Papers by ayush pandey
International Journal of Robust and Nonlinear Control
Model reduction methods usually focus on the error performance analysis; however, in presence of ... more Model reduction methods usually focus on the error performance analysis; however, in presence of uncertainties, it is important to analyze the robustness properties of the error in model reduction as well. In this paper, we give robustness guarantees for structured model reduction of linear and nonlinear dynamical systems under parametric uncertainties. In particular, we consider a model reduction where the states in the reduced model are a strict subset of the states of the full model, and the dynamics for all other states are collapsed to zero (similar to quasi-steady state approximation). We show two approaches to compute a robustness metric for any such model reduction-a direct linear analysis method for linear dynamics and a sensitivity analysis based approach that also works for nonlinear dynamics. We also prove that for linear systems, both methods give equivalent results.
The mammalian gut contains trillions of microbes that interact with host cells and monitor change... more The mammalian gut contains trillions of microbes that interact with host cells and monitor changes in the environment. Opportunistic pathogens exploit environmental conditions to stimulate their growth and virulence, leading to a resurgence of chronic disorders such as inflammatory bowel disease (IBD). Current therapies are effective in less than 30% of patients due to the lack of adherence to prescription schedules and overall, off-target effects. Smart microbial therapeutics can be engineered to colonize the gut, providingin situsurveillance and conditional disease modulation. However, many current engineered microbes can only respond to single gut environmental factors, limiting their effectiveness. In this work, we implement the previously characterized split activator AND logic gate in the probioticE. colistrain Nissle 1917. Our system can respond to two input signals: the inflammatory biomarker tetrathionate and a second input signal, IPTG. We report 4-6 fold induction with mi...
Biochemical interactions in systems and synthetic biology are often modeled with chemical reactio... more Biochemical interactions in systems and synthetic biology are often modeled with chemical reaction networks (CRNs). CRNs provide a principled modeling environment capable of expressing a huge range of biochemical processes. In this paper, we present a software toolbox, written in Python, that compiles high-level design specifications represented using a modular library of biochemical parts, mechanisms, and contexts to CRN implementations. This compilation process offers four advantages. First, the building of the actual CRN representation is automatic and outputs Systems Biology Markup Language (SBML) models compatible with numerous simulators. Second, a library of modular biochemical components allows for different architectures and implementations of biochemical circuits to be represented succinctly with design choices propagated throughout the underlying CRN automatically. This prevents the often occurring mismatch between high-level designs and model dynamics. Third, high-level ...
We present an automated model reduction algorithm that uses quasi-steady state approximation to m... more We present an automated model reduction algorithm that uses quasi-steady state approximation to minimize the error between the desired outputs. Additionally, the algorithm minimizes the sensitivity of the error with respect to parameters to ensure robust performance of the reduced model in the presence of parametric uncertainties. We develop the theory for this model reduction algorithm and present the implementation of the algorithm that can be used to perform model reduction of given SBML models. To demonstrate the utility of this algorithm, we consider the design of a synthetic biological circuit to control the population density and composition of a consortium consisting of two different cell strains. We show how the model reduction algorithm can be used to guide the design and analysis of this circuit.
We present a Python-based software package to automatically obtain phenomenological models of inp... more We present a Python-based software package to automatically obtain phenomenological models of input-controlled synthetic biological circuits that guide the design using chemical reaction-level descriptive models. From the parts and mechanism description of a synthetic biological circuit, it is easy to obtain a chemical reaction model of the circuit under the assumptions of mass-action kinetics using various existing tools. However, using these models to guide design decisions during an experiment is difficult due to a large number of reaction rate parameters and species in the model. Hence, phenomenological models are often developed that describe the effective relationships among the circuit inputs, outputs, and only the key states and parameters. In this paper, we present an algorithm to obtain these phenomenological models in an automated manner using a Python package for circuits with inputs that control the desired outputs. This model reduction approach combines the common assu...
As studies continue to demonstrate how our health is related to the status of our various commens... more As studies continue to demonstrate how our health is related to the status of our various commensal microbiomes, synthetic biologists are developing tools and approaches to control these microbiomes and stabilize healthy states or remediate unhealthy ones. Building on previous work to control bacterial communities, we have constructed a synthetic two-member bacterial consortium engineered to reach population density and composition steady states set by inducer inputs. We detail a screening strategy to search functional parameter space in this high-complexity genetic circuit as well as initial testing of a functional two-member circuit.We demonstrate non-independent changes in total population density and composition steady states with a limited set of varying inducer concentrations. After a dilution to perturb the system from its steady state, density and composition steady states are not regained. Modeling and simulation suggest a need for increased degradation of intercellular sig...
In systems and synthetic biology, it is common to build chemical reaction network (CRN) models of... more In systems and synthetic biology, it is common to build chemical reaction network (CRN) models of biochemical circuits and networks. Although automation and other high-throughput techniques have led to an abundance of data enabling data-driven quantitative modeling and parameter estimation, the intense amount of simulation needed for these methods still frequently results in a computational bottleneck. Here we present bioscrape (Bio-circuit Stochastic Single-cell Reaction Analysis and Parameter Estimation) - a Python package for fast and flexible modeling and simulation of highly customizable chemical reaction networks. Specifically, bioscrape supports deterministic and stochastic simulations, which can incorporate delay, cell growth, and cell division. All functionalities - reaction models, simulation algorithms, cell growth models, partioning models, and Bayesian inference - are implemented as interfaces in an easily extensible and modular object-oriented framework. Models can be ...
We derive phenomenological models of gene expression from a mechanistic description of chemical r... more We derive phenomenological models of gene expression from a mechanistic description of chemical reactions using an automated model reduction method. Using this method, we get analytical descriptions and computational performance guarantees to compare the reduced dynamics with the full models. We develop a new two-state model with the dynamics of the available free ribosomes in the system and the protein concentration. We show that this new two-state model captures the detailed mass-action kinetics of the chemical reaction network under various biologically plausible conditions on model parameters. On comparing the performance of this model with the commonly used mRNA transcript-protein dynamical model for gene expression, we analytically show that the free ribosome and protein model has superior error and robustness performance.
International Journal of Scientific and Research Publications (IJSRP)
Here we report a case scenario where a 19 year old female presented with complaints of Pain over ... more Here we report a case scenario where a 19 year old female presented with complaints of Pain over bilateral buttocks radiating down to the right thigh to foot x 4 months, persistent, exaggerated by squatting/ working, Constipation x 4 months, Weight loss x 1 month, Urinary retention x 15 days, continuous dribbling and Loss of sensation over bilateral buttocks, inability to feel clothes or hot/cold sensation. She was diagnosed to have a sacral tumor and was managed a multidisciplinary approach.
Applied Physics Letters, 1991
International Journal of Robust and Nonlinear Control
Model reduction methods usually focus on the error performance analysis; however, in presence of ... more Model reduction methods usually focus on the error performance analysis; however, in presence of uncertainties, it is important to analyze the robustness properties of the error in model reduction as well. In this paper, we give robustness guarantees for structured model reduction of linear and nonlinear dynamical systems under parametric uncertainties. In particular, we consider a model reduction where the states in the reduced model are a strict subset of the states of the full model, and the dynamics for all other states are collapsed to zero (similar to quasi-steady state approximation). We show two approaches to compute a robustness metric for any such model reduction-a direct linear analysis method for linear dynamics and a sensitivity analysis based approach that also works for nonlinear dynamics. We also prove that for linear systems, both methods give equivalent results.
The mammalian gut contains trillions of microbes that interact with host cells and monitor change... more The mammalian gut contains trillions of microbes that interact with host cells and monitor changes in the environment. Opportunistic pathogens exploit environmental conditions to stimulate their growth and virulence, leading to a resurgence of chronic disorders such as inflammatory bowel disease (IBD). Current therapies are effective in less than 30% of patients due to the lack of adherence to prescription schedules and overall, off-target effects. Smart microbial therapeutics can be engineered to colonize the gut, providingin situsurveillance and conditional disease modulation. However, many current engineered microbes can only respond to single gut environmental factors, limiting their effectiveness. In this work, we implement the previously characterized split activator AND logic gate in the probioticE. colistrain Nissle 1917. Our system can respond to two input signals: the inflammatory biomarker tetrathionate and a second input signal, IPTG. We report 4-6 fold induction with mi...
Biochemical interactions in systems and synthetic biology are often modeled with chemical reactio... more Biochemical interactions in systems and synthetic biology are often modeled with chemical reaction networks (CRNs). CRNs provide a principled modeling environment capable of expressing a huge range of biochemical processes. In this paper, we present a software toolbox, written in Python, that compiles high-level design specifications represented using a modular library of biochemical parts, mechanisms, and contexts to CRN implementations. This compilation process offers four advantages. First, the building of the actual CRN representation is automatic and outputs Systems Biology Markup Language (SBML) models compatible with numerous simulators. Second, a library of modular biochemical components allows for different architectures and implementations of biochemical circuits to be represented succinctly with design choices propagated throughout the underlying CRN automatically. This prevents the often occurring mismatch between high-level designs and model dynamics. Third, high-level ...
We present an automated model reduction algorithm that uses quasi-steady state approximation to m... more We present an automated model reduction algorithm that uses quasi-steady state approximation to minimize the error between the desired outputs. Additionally, the algorithm minimizes the sensitivity of the error with respect to parameters to ensure robust performance of the reduced model in the presence of parametric uncertainties. We develop the theory for this model reduction algorithm and present the implementation of the algorithm that can be used to perform model reduction of given SBML models. To demonstrate the utility of this algorithm, we consider the design of a synthetic biological circuit to control the population density and composition of a consortium consisting of two different cell strains. We show how the model reduction algorithm can be used to guide the design and analysis of this circuit.
We present a Python-based software package to automatically obtain phenomenological models of inp... more We present a Python-based software package to automatically obtain phenomenological models of input-controlled synthetic biological circuits that guide the design using chemical reaction-level descriptive models. From the parts and mechanism description of a synthetic biological circuit, it is easy to obtain a chemical reaction model of the circuit under the assumptions of mass-action kinetics using various existing tools. However, using these models to guide design decisions during an experiment is difficult due to a large number of reaction rate parameters and species in the model. Hence, phenomenological models are often developed that describe the effective relationships among the circuit inputs, outputs, and only the key states and parameters. In this paper, we present an algorithm to obtain these phenomenological models in an automated manner using a Python package for circuits with inputs that control the desired outputs. This model reduction approach combines the common assu...
As studies continue to demonstrate how our health is related to the status of our various commens... more As studies continue to demonstrate how our health is related to the status of our various commensal microbiomes, synthetic biologists are developing tools and approaches to control these microbiomes and stabilize healthy states or remediate unhealthy ones. Building on previous work to control bacterial communities, we have constructed a synthetic two-member bacterial consortium engineered to reach population density and composition steady states set by inducer inputs. We detail a screening strategy to search functional parameter space in this high-complexity genetic circuit as well as initial testing of a functional two-member circuit.We demonstrate non-independent changes in total population density and composition steady states with a limited set of varying inducer concentrations. After a dilution to perturb the system from its steady state, density and composition steady states are not regained. Modeling and simulation suggest a need for increased degradation of intercellular sig...
In systems and synthetic biology, it is common to build chemical reaction network (CRN) models of... more In systems and synthetic biology, it is common to build chemical reaction network (CRN) models of biochemical circuits and networks. Although automation and other high-throughput techniques have led to an abundance of data enabling data-driven quantitative modeling and parameter estimation, the intense amount of simulation needed for these methods still frequently results in a computational bottleneck. Here we present bioscrape (Bio-circuit Stochastic Single-cell Reaction Analysis and Parameter Estimation) - a Python package for fast and flexible modeling and simulation of highly customizable chemical reaction networks. Specifically, bioscrape supports deterministic and stochastic simulations, which can incorporate delay, cell growth, and cell division. All functionalities - reaction models, simulation algorithms, cell growth models, partioning models, and Bayesian inference - are implemented as interfaces in an easily extensible and modular object-oriented framework. Models can be ...
We derive phenomenological models of gene expression from a mechanistic description of chemical r... more We derive phenomenological models of gene expression from a mechanistic description of chemical reactions using an automated model reduction method. Using this method, we get analytical descriptions and computational performance guarantees to compare the reduced dynamics with the full models. We develop a new two-state model with the dynamics of the available free ribosomes in the system and the protein concentration. We show that this new two-state model captures the detailed mass-action kinetics of the chemical reaction network under various biologically plausible conditions on model parameters. On comparing the performance of this model with the commonly used mRNA transcript-protein dynamical model for gene expression, we analytically show that the free ribosome and protein model has superior error and robustness performance.
International Journal of Scientific and Research Publications (IJSRP)
Here we report a case scenario where a 19 year old female presented with complaints of Pain over ... more Here we report a case scenario where a 19 year old female presented with complaints of Pain over bilateral buttocks radiating down to the right thigh to foot x 4 months, persistent, exaggerated by squatting/ working, Constipation x 4 months, Weight loss x 1 month, Urinary retention x 15 days, continuous dribbling and Loss of sensation over bilateral buttocks, inability to feel clothes or hot/cold sensation. She was diagnosed to have a sacral tumor and was managed a multidisciplinary approach.
Applied Physics Letters, 1991