Q.1 Which of the following best describes the purpose of SBML (Systems Biology Markup Language) in model simulation?
To provide a graphical user interface for data analysis
To store and exchange computational models of biological processes
To simulate electrical circuits directly
To generate synthetic DNA sequences
Explanation - SBML is an XML‑based format that enables sharing of quantitative models (e.g., ODEs, stochastic models) across different software tools.
Correct answer is: To store and exchange computational models of biological processes
Q.2 In an electrical‑circuit analogy of a gene regulatory network, a resistor most closely represents:
mRNA degradation rate
Transcriptional activation strength
Protein synthesis delay
Cell membrane capacitance
Explanation - In the analogy, resistance opposes flow, akin to degradation removing molecules from the system.
Correct answer is: mRNA degradation rate
Q.3 The Gillespie Stochastic Simulation Algorithm (SSA) is primarily used to:
Solve deterministic ODE models
Compute steady‑state flux balance analysis
Generate exact trajectories of chemically reacting systems with small copy numbers
Design synthetic gene circuits using Boolean logic
Explanation - SSA samples reaction times and events according to the exact stochastic master equation, suitable for low‑copy-number species.
Correct answer is: Generate exact trajectories of chemically reacting systems with small copy numbers
Q.4 When converting a biochemical network into a set of ordinary differential equations (ODEs), which assumption is typically made?
All reactions follow Michaelis–Menten kinetics
Molecule numbers are large enough that stochastic fluctuations can be ignored
Enzyme concentrations remain constant over time
The system is at thermodynamic equilibrium
Explanation - Deterministic ODE models assume continuous concentrations, which is valid when copy numbers are high and random noise averages out.
Correct answer is: Molecule numbers are large enough that stochastic fluctuations can be ignored
Q.5 In a compartmental model of a signaling pathway, the term ‘compartment’ most closely corresponds to:
A single protein domain
A spatial region such as cytosol or nucleus
A gene promoter
An electrical resistor
Explanation - Compartments separate species based on location, allowing different concentrations and reaction rates in each region.
Correct answer is: A spatial region such as cytosol or nucleus
Q.6 Which numerical integration method is most appropriate for stiff ODE systems often encountered in metabolic network simulations?
Euler's explicit method
Runge–Kutta 4th order
Backward differentiation formula (BDF)
Monte Carlo integration
Explanation - BDF is an implicit method designed for stiff systems, providing stability even with large time steps.
Correct answer is: Backward differentiation formula (BDF)
Q.7 Parameter sensitivity analysis in a systems biology model helps to:
Identify which parameters most influence model output
Reduce the number of species in the network
Convert a stochastic model into a deterministic one
Generate synthetic gene sequences
Explanation - Sensitivity analysis quantifies how variations in parameters affect model predictions, guiding experimental design and model refinement.
Correct answer is: Identify which parameters most influence model output
Q.8 In Simulink, a ‘Transfer Function’ block is most suitable for representing:
A gene transcription rate law
A linear time‑invariant system such as a simple RC circuit analogue of a degradation process
A stochastic reaction network
A Boolean logic gate
Explanation - Transfer functions model linear relationships between input and output in the Laplace domain, similar to RC circuit dynamics.
Correct answer is: A linear time‑invariant system such as a simple RC circuit analogue of a degradation process
Q.9 The Hill coefficient in a Hill function describing transcriptional activation primarily reflects:
The rate of mRNA degradation
Cooperativity of transcription factor binding
The diffusion coefficient of the protein
The electrical resistance of the cell membrane
Explanation - A Hill coefficient >1 indicates cooperative binding, shaping the sigmoidal response curve of gene expression.
Correct answer is: Cooperativity of transcription factor binding
Q.10 When fitting model parameters to experimental time‑course data using least‑squares optimization, the objective function minimizes:
The sum of absolute differences between simulated and measured values
The sum of squared differences between simulated and measured values
The maximum absolute error
The number of model parameters
Explanation - Least‑squares aims to minimize the squared residuals, providing a statistically optimal fit under Gaussian noise assumptions.
Correct answer is: The sum of squared differences between simulated and measured values
Q.11 In a Boolean model of a gene regulatory network, the state of a gene at the next time step is determined by:
Continuous concentration values
A logical rule (e.g., AND, OR, NOT) applied to the states of its regulators
A set of differential equations
Random sampling from a probability distribution
Explanation - Boolean models discretize gene activity to ON/OFF and update it using logical functions based on inputs.
Correct answer is: A logical rule (e.g., AND, OR, NOT) applied to the states of its regulators
Q.12 Which of the following is a key advantage of using a hybrid (deterministic‑stochastic) simulation approach?
It eliminates the need for parameter estimation
It allows fast simulation of high‑abundance species while accurately capturing noise in low‑abundance species
It guarantees analytical solutions for all species
It automatically converts ODEs to partial differential equations
Explanation - Hybrid methods treat abundant species deterministically (ODEs) and scarce species stochastically, balancing speed and accuracy.
Correct answer is: It allows fast simulation of high‑abundance species while accurately capturing noise in low‑abundance species
Q.13 In the context of model reduction, the quasi‑steady‑state approximation (QSSA) assumes that:
All reactions occur at the same rate
Intermediate complexes reach a steady state much faster than the overall system dynamics
The system has reached thermodynamic equilibrium
Enzyme concentrations are negligible
Explanation - QSSA removes fast variables by assuming they quickly equilibrate, simplifying the model while preserving slower dynamics.
Correct answer is: Intermediate complexes reach a steady state much faster than the overall system dynamics
Q.14 Which of the following metrics is commonly used to assess the goodness‑of‑fit for a model calibrated to time‑series data?
Root‑mean‑square error (RMSE)
Signal‑to‑noise ratio (SNR)
Eigenvalue magnitude
Capacitance value
Explanation - RMSE quantifies the average magnitude of prediction errors, directly reflecting fit quality for continuous data.
Correct answer is: Root‑mean‑square error (RMSE)
Q.15 When modeling diffusion of a signaling molecule between two compartments, the flux J can be expressed as:
J = k * [A]
J = D * (C1 - C2) / d
J = Vmax * [S] / (Km + [S])
J = R * I
Explanation - Fick’s law states that diffusive flux is proportional to the concentration gradient (C1‑C2) divided by the distance d, with diffusion coefficient D.
Correct answer is: J = D * (C1 - C2) / d
Q.16 In the context of synthetic biology, a ‘toggle switch’ can be mathematically modeled using:
Two mutually repressing Hill functions
A single linear ODE
A set of independent Poisson processes
An RC low‑pass filter
Explanation - A bistable toggle switch arises from two genes that inhibit each other; Hill functions capture the cooperative repression.
Correct answer is: Two mutually repressing Hill functions
Q.17 The term ‘identifiability’ in model parameter estimation refers to:
Whether a model can be simulated on a computer
Whether unique parameter values can be inferred from given data
Whether the model obeys conservation laws
Whether the model uses SBML format
Explanation - Identifiability analysis determines if data contain enough information to estimate parameters uniquely; lack of identifiability leads to ambiguous fits.
Correct answer is: Whether unique parameter values can be inferred from given data
Q.18 A ‘phase portrait’ is useful for:
Visualizing trajectories of dynamical systems in state‑space
Displaying the DNA sequence of a gene
Measuring electrical resistance in a circuit
Calculating the probability of reaction events
Explanation - Phase portraits plot variables against each other, revealing attractors, limit cycles, and stability properties.
Correct answer is: Visualizing trajectories of dynamical systems in state‑space
Q.19 Which of the following best describes the ‘master equation’ in stochastic modeling?
A set of algebraic equations for steady‑state concentrations
A differential equation describing the time evolution of the probability distribution over system states
A matrix describing electrical conductance
An empirical rule for fitting data
Explanation - The chemical master equation governs how probabilities of each molecular count configuration change over time.
Correct answer is: A differential equation describing the time evolution of the probability distribution over system states
Q.20 In a reaction network, the ‘stoichiometric matrix’ S relates:
Reaction rates to metabolite concentrations
Species changes to reaction fluxes
Electrical voltage to current
Gene expression to promoter strength
Explanation - Each column of S corresponds to a reaction, each row to a species; the product S·v gives the net change in species concentrations.
Correct answer is: Species changes to reaction fluxes
Q.21 When performing a global sensitivity analysis using Sobol indices, a high first‑order index for a parameter indicates:
The parameter has a strong independent effect on model output variance
The parameter is non‑identifiable
The model is stiff
The parameter only interacts with others
Explanation - First‑order Sobol index quantifies the fraction of output variance explained by that parameter alone.
Correct answer is: The parameter has a strong independent effect on model output variance
Q.22 In an electrical analogue of a metabolic pathway, a capacitor typically represents:
Enzyme turnover number (kcat)
Accumulation of a metabolite (concentration storage)
Resistance to substrate flow
Signal attenuation
Explanation - Capacitance stores charge; analogously, a capacitor stores the ‘amount’ of a species, modeling its concentration dynamics.
Correct answer is: Accumulation of a metabolite (concentration storage)
Q.23 Which of the following is a common method for generating initial conditions for a stochastic simulation when experimental data are unavailable?
Assume all species start at zero concentration
Sample from a uniform distribution over a biologically plausible range
Set all concentrations to one molar
Use the steady‑state solution of the deterministic model
Explanation - Uniform sampling provides diverse starting points, allowing exploration of possible trajectories when data are missing.
Correct answer is: Sample from a uniform distribution over a biologically plausible range
Q.24 The term ‘bifurcation’ in dynamical systems refers to:
A point where the system’s steady state splits into multiple branches as a parameter changes
A type of electrical circuit
A statistical test for model fit
A method for solving ODEs
Explanation - Bifurcations indicate qualitative changes in system behavior, such as the emergence of bistability or oscillations.
Correct answer is: A point where the system’s steady state splits into multiple branches as a parameter changes
Q.25 When calibrating a model with Bayesian inference, the posterior distribution combines:
Prior knowledge and the likelihood of observed data
The deterministic solution and stochastic noise
The stoichiometric matrix and the Jacobian
Capacitance and resistance values
Explanation - Bayes' theorem updates prior beliefs with data likelihood to produce the posterior probability distribution over parameters.
Correct answer is: Prior knowledge and the likelihood of observed data
Q.26 In model verification, which of the following tests ensures that mass is conserved in a closed biochemical system?
Unit testing of individual functions
Checking that the sum of species derivatives equals zero when no inflow/outflow reactions exist
Running a Monte Carlo simulation
Measuring the electrical resistance of the circuit analogue
Explanation - Mass conservation requires that, in a closed system, total mass (or molecule count) does not change over time.
Correct answer is: Checking that the sum of species derivatives equals zero when no inflow/outflow reactions exist
Q.27 The ‘Jacobian matrix’ of a system of ODEs is used to:
Calculate reaction rates
Determine local stability of steady states
Generate stochastic trajectories
Convert the model to SBML format
Explanation - Eigenvalues of the Jacobian evaluated at a steady state reveal whether perturbations grow or decay.
Correct answer is: Determine local stability of steady states
Q.28 A ‘limit cycle’ in a dynamical model indicates:
A trajectory that diverges to infinity
A stable, periodic oscillation
An equilibrium point with zero eigenvalues
A stochastic fluctuation
Explanation - Limit cycles are closed orbits attracting nearby trajectories, representing sustained rhythmic behavior (e.g., circadian clocks).
Correct answer is: A stable, periodic oscillation
Q.29 When modeling a gene circuit with delay differential equations (DDEs), the delay term typically accounts for:
Instantaneous transcription
Finite time required for transcription, translation, or transport
Diffusion of ions across the membrane
Electrical capacitance
Explanation - Delays capture the lag between a signal (e.g., promoter activation) and the appearance of the protein product.
Correct answer is: Finite time required for transcription, translation, or transport
Q.30 In a kinetic model, the Michaelis–Menten constant (Km) is defined as:
The substrate concentration at which the reaction rate is half of Vmax
The maximum reaction velocity
The rate of enzyme synthesis
The diffusion coefficient of the substrate
Explanation - Km provides a measure of enzyme affinity for its substrate; lower Km indicates higher affinity.
Correct answer is: The substrate concentration at which the reaction rate is half of Vmax
Q.31 Which software environment is specifically designed for the simulation of biochemical reaction networks and supports SBML import/export?
MATLAB Simulink
COPASI
ANSYS HFSS
AutoCAD
Explanation - COPASI (COmplex PAthway SImulator) offers deterministic, stochastic, and hybrid simulation methods and native SBML handling.
Correct answer is: COPASI
Q.32 In a flux balance analysis (FBA) model, the objective function is usually:
Minimization of enzyme concentrations
Maximization of biomass production or a specific metabolite flux
Minimization of electrical resistance
Maximization of stochastic noise
Explanation - FBA optimizes a linear objective (e.g., growth rate) subject to stoichiometric constraints at steady state.
Correct answer is: Maximization of biomass production or a specific metabolite flux
Q.33 When a model exhibits ‘parameter sloppiness’, it means that:
All parameters have the same numerical value
The model is insensitive to many parameter variations, making precise estimation difficult
The model cannot be simulated numerically
The parameters are all highly correlated
Explanation - Sloppy models have directions in parameter space where changes cause little effect on outputs, leading to large uncertainties.
Correct answer is: The model is insensitive to many parameter variations, making precise estimation difficult
Q.34 Which of the following statements about the Euler–Maruyama method is true?
It is an exact solver for the chemical master equation
It is a numerical scheme for integrating stochastic differential equations (SDEs)
It can only be used for deterministic ODEs
It automatically identifies bifurcations
Explanation - Euler–Maruyama extends Euler’s method to include stochastic (noise) terms, approximating SDE trajectories.
Correct answer is: It is a numerical scheme for integrating stochastic differential equations (SDEs)
Q.35 In a model of calcium signaling, the term ‘buffering’ refers to:
Electrical resistance in the membrane
Binding of calcium ions to proteins that reduces free calcium concentration
Diffusion of calcium across the nucleus
Generation of action potentials
Explanation - Buffers sequester calcium, shaping the temporal profile of calcium spikes.
Correct answer is: Binding of calcium ions to proteins that reduces free calcium concentration
Q.36 The purpose of performing a ‘parameter sweep’ in simulation studies is to:
Identify the optimal algorithm for solving ODEs
Explore model behavior over a range of parameter values
Convert the model to a Boolean network
Measure electrical power consumption
Explanation - Parameter sweeps systematically vary parameters to assess robustness, locate regimes of interest, or generate phase diagrams.
Correct answer is: Explore model behavior over a range of parameter values
Q.37 In a linearized system, eigenvalues with positive real parts indicate:
Stable equilibrium
Unstable equilibrium (growth of perturbations)
Oscillatory but stable behavior
Conservation of mass
Explanation - Positive real parts of eigenvalues cause exponential growth of small disturbances, leading to instability.
Correct answer is: Unstable equilibrium (growth of perturbations)
Q.38 Which of the following best describes a ‘feedforward loop’ (FFL) in a gene regulatory network?
A motif where a regulator controls a target directly and also indirectly through a second regulator
A loop that only contains negative feedback
A circuit that stores charge like a capacitor
A stochastic process with Poisson statistics
Explanation - FFLs can filter signals and generate pulse-like responses; they consist of a direct and an indirect path from regulator to target.
Correct answer is: A motif where a regulator controls a target directly and also indirectly through a second regulator
Q.39 In the context of model validation, a ‘cross‑validation’ approach involves:
Using the same data for both training and testing
Dividing data into subsets, training on some and testing on the others
Simulating the model without any data
Measuring electrical currents in the circuit analogue
Explanation - Cross‑validation assesses predictive performance by rotating training and validation sets, reducing overfitting.
Correct answer is: Dividing data into subsets, training on some and testing on the others
Q.40 When a model includes a ‘Hill function’ with a coefficient n = 1, the response curve is:
Highly cooperative (sigmoidal)
Linear (Michaelis–Menten like)
Exponential
Logarithmic
Explanation - When n = 1, the Hill function reduces to a hyperbolic Michaelis–Menten form without cooperativity.
Correct answer is: Linear (Michaelis–Menten like)
Q.41 Which of the following is a typical output of a stochastic simulation of a gene network?
A single deterministic trajectory
A distribution of possible molecule counts over time
An electrical waveform
A Boolean truth table
Explanation - Stochastic simulations generate many possible realizations, allowing estimation of probability distributions for species counts.
Correct answer is: A distribution of possible molecule counts over time
Q.42 In the context of metabolic control analysis, the control coefficient measures:
The sensitivity of a system variable (e.g., flux) to a parameter change (e.g., enzyme activity)
The electrical resistance of a metabolic pathway
The number of genes in a network
The probability of a reaction occurring
Explanation - Control coefficients quantify how changes in enzyme activities affect steady‑state fluxes or concentrations.
Correct answer is: The sensitivity of a system variable (e.g., flux) to a parameter change (e.g., enzyme activity)
Q.43 Which method is most suitable for estimating parameters of a highly nonlinear model where the likelihood surface has many local minima?
Gradient descent
Genetic algorithms or other evolutionary optimization techniques
Simple linear regression
Direct analytical solution
Explanation - Global search heuristics like genetic algorithms can escape local minima and explore the parameter space broadly.
Correct answer is: Genetic algorithms or other evolutionary optimization techniques
Q.44 When modeling an electrical analog of a metabolic pathway, the product RC (resistance × capacitance) has units of:
Volts
Amperes
Seconds
Moles
Explanation - RC is the time constant of an RC circuit, governing how quickly voltage (or concentration analogue) changes.
Correct answer is: Seconds
Q.45 A ‘Monte Carlo’ approach in model analysis is primarily used for:
Deterministic integration of ODEs
Random sampling to assess uncertainty or explore parameter space
Solving linear algebraic equations
Designing electronic circuits
Explanation - Monte Carlo methods generate many random draws to approximate distributions, propagate uncertainty, or perform global sensitivity.
Correct answer is: Random sampling to assess uncertainty or explore parameter space
Q.46 In a biochemical network, the term ‘flux’ refers to:
Electrical current
Rate at which a reaction converts substrates to products (usually in mol·L⁻¹·s⁻¹)
The amount of DNA in a cell
The diffusion coefficient of a metabolite
Explanation - Flux quantifies the flow of material through a reaction pathway.
Correct answer is: Rate at which a reaction converts substrates to products (usually in mol·L⁻¹·s⁻¹)
Q.47 Which of the following is a characteristic of a ‘limit point’ (or saddle‑node) bifurcation?
Two steady states collide and annihilate each other as a parameter is varied
A periodic orbit appears from a steady state
The system becomes chaotic
The Jacobian matrix becomes diagonal
Explanation - Saddle‑node bifurcations create or destroy pairs of equilibria, leading to abrupt changes in system behavior.
Correct answer is: Two steady states collide and annihilate each other as a parameter is varied
Q.48 In the context of model reduction, the term ‘lumped parameter’ means:
A parameter that combines several detailed processes into a single effective term
A parameter that is set to zero
A parameter that varies randomly
A parameter that is measured in volts
Explanation - Lumping simplifies a model by aggregating multiple steps into one effective rate or capacity.
Correct answer is: A parameter that combines several detailed processes into a single effective term
Q.49 The ‘Laplace transform’ is useful in systems biology modeling because it:
Converts time‑domain differential equations into algebraic equations in the s‑domain
Measures the concentration of metabolites directly
Provides a stochastic description of reactions
Generates random numbers
Explanation - Laplace transforms simplify linear ODE analysis and facilitate the design of control strategies.
Correct answer is: Converts time‑domain differential equations into algebraic equations in the s‑domain
Q.50 When using the ‘Method of Lines’ to solve partial differential equations (PDEs) in a spatially distributed model, the spatial dimension is:
Ignored completely
Discretized into a set of ordinary differential equations
Converted into a stochastic process
Represented by a single resistor
Explanation - The Method of Lines discretizes space, leaving time continuous, yielding a large ODE system that can be integrated numerically.
Correct answer is: Discretized into a set of ordinary differential equations
Q.51 Which of the following statements about ‘deterministic chaos’ in a biochemical model is correct?
It only occurs in stochastic models
It arises from sensitivity to initial conditions in deterministic nonlinear systems
It is prevented by adding noise
It requires the system to be linear
Explanation - Chaotic dynamics can emerge in deterministic nonlinear ODEs, showing apparent randomness despite no stochastic component.
Correct answer is: It arises from sensitivity to initial conditions in deterministic nonlinear systems
Q.52 In a model that includes gene expression and protein degradation, the overall effective degradation rate of the protein is:
The sum of transcription and translation rates
The product of mRNA degradation rate and protein degradation rate
The protein degradation rate only (assuming translation is fast)
Zero, because proteins never degrade
Explanation - Effective protein loss depends primarily on its own degradation; mRNA turnover influences production but not degradation directly.
Correct answer is: The protein degradation rate only (assuming translation is fast)
Q.53 A ‘bifurcation diagram’ typically plots:
Time versus concentration for a single simulation
Steady‑state values of a variable against a bifurcation parameter
The Jacobian matrix entries
Voltage versus current
Explanation - Bifurcation diagrams show how equilibria change as a control parameter varies, revealing branches, stability, and critical points.
Correct answer is: Steady‑state values of a variable against a bifurcation parameter
Q.54 When a model is expressed in the form dX/dt = AX + B, where A is a matrix, the solution can be written using:
Matrix exponential e^{At} multiplied by the initial condition plus a particular solution
Fourier series
Laplace transform of B only
Logarithmic integration
Explanation - The linear system solution uses the matrix exponential to propagate the homogeneous part, plus a particular solution for the forcing term B.
Correct answer is: Matrix exponential e^{At} multiplied by the initial condition plus a particular solution
Q.55 In a synthetic gene circuit, the term ‘inducer’ refers to:
A molecule that activates gene expression by binding to a regulatory protein
An electrical component that stores charge
A type of resistor
A stochastic noise source
Explanation - Inducers modulate transcription factors, altering promoter activity and thereby controlling circuit behavior.
Correct answer is: A molecule that activates gene expression by binding to a regulatory protein
Q.56 When performing a ‘steady‑state analysis’ of a deterministic ODE model, you set:
All time derivatives to zero and solve the resulting algebraic equations
All parameters to one
All species concentrations to zero
All reaction rates to infinity
Explanation - Steady state occurs when concentrations no longer change; mathematically, dX/dt = 0 for every state variable.
Correct answer is: All time derivatives to zero and solve the resulting algebraic equations
Q.57 Which of the following best describes the role of ‘mass action kinetics’ in reaction rate laws?
Rate is proportional to the product of reactant concentrations raised to their stoichiometric coefficients
Rate is independent of concentration
Rate follows a sinusoidal function
Rate depends only on temperature
Explanation - Mass action law states that reaction velocity = k * ∏[reactants]^{stoichiometry}.
Correct answer is: Rate is proportional to the product of reactant concentrations raised to their stoichiometric coefficients
Q.58 In a multi‑scale model that couples intracellular signaling (fast) with tissue growth (slow), an appropriate numerical strategy is to:
Use the same small time step for both scales
Apply operator splitting: integrate fast dynamics with a small step, slow dynamics with a larger step
Ignore the fast dynamics
Only simulate the tissue level
Explanation - Operator splitting allows each subsystem to be solved with suitable step sizes, improving efficiency while preserving accuracy.
Correct answer is: Apply operator splitting: integrate fast dynamics with a small step, slow dynamics with a larger step
Q.59 The ‘Cramer‑Rao bound’ in parameter estimation provides:
The maximum possible variance of an unbiased estimator
The minimum possible variance of an unbiased estimator
The exact parameter values
The deterministic solution of the model
Explanation - Cramer‑Rao sets a lower bound on the variance; it indicates the best achievable precision given data.
Correct answer is: The minimum possible variance of an unbiased estimator
Q.60 When a model includes ‘delayed negative feedback’, the typical dynamic behavior observed is:
Exponential growth without bound
Damped or sustained oscillations depending on delay length and feedback strength
Immediate steady‑state convergence
Random noise
Explanation - Delay in negative feedback can introduce phase lag, leading to oscillatory dynamics.
Correct answer is: Damped or sustained oscillations depending on delay length and feedback strength
Q.61 Which of the following is NOT a typical output format for model exchange in computational biology?
SBML
MATLAB .m file
CellML
FASTA
Explanation - FASTA is a format for nucleotide or protein sequences, not for model exchange.
Correct answer is: FASTA
Q.62 In a deterministic ODE model, the term ‘stiffness’ generally arises when:
All reactions have identical rate constants
There is a large disparity between the fastest and slowest timescales
The system is linear
The model contains no feedback loops
Explanation - Stiff systems contain rapid and slow dynamics; explicit integrators require prohibitively small steps for stability.
Correct answer is: There is a large disparity between the fastest and slowest timescales
Q.63 A ‘deterministic compartment model’ of drug pharmacokinetics typically uses:
Partial differential equations
Ordinary differential equations describing rates of transfer between compartments
Stochastic simulation algorithms
Boolean logic
Explanation - Compartmental PK models represent body spaces as compartments linked by rate constants, modeled with ODEs.
Correct answer is: Ordinary differential equations describing rates of transfer between compartments
Q.64 In the context of model predictive control (MPC) applied to a synthetic biological system, the controller:
Predicts future system behavior over a horizon and optimizes control inputs accordingly
Solves the master equation analytically
Generates random perturbations
Measures electrical power consumption
Explanation - MPC uses a model to forecast dynamics and compute optimal inputs (e.g., inducer concentrations) at each step.
Correct answer is: Predicts future system behavior over a horizon and optimizes control inputs accordingly
Q.65 When performing a ‘profile likelihood’ analysis for a parameter, the method:
Samples the full parameter space uniformly
Fixes the parameter of interest at various values and re‑optimizes the remaining parameters to assess likelihood
Computes the Jacobian matrix eigenvalues
Uses Fourier transform
Explanation - Profile likelihood provides confidence intervals by exploring how the fit deteriorates as a single parameter is varied.
Correct answer is: Fixes the parameter of interest at various values and re‑optimizes the remaining parameters to assess likelihood
Q.66 In a gene regulatory network, a ‘positive feedback loop’ can lead to:
Bistability, where two stable steady states exist
Only a single stable steady state
Immediate decay of all species
Random noise amplification without any deterministic effect
Explanation - Positive feedback can create two alternative stable states, enabling switch‑like behavior.
Correct answer is: Bistability, where two stable steady states exist
Q.67 Which of the following is a common criterion for model selection when comparing multiple competing models?
Highest number of parameters
Lowest Akaike Information Criterion (AIC) value
Largest residual sum of squares
Most complex mathematical form
Explanation - AIC balances goodness‑of‑fit with model complexity; lower AIC indicates a better trade‑off.
Correct answer is: Lowest Akaike Information Criterion (AIC) value
Q.68 In a hybrid stochastic‑deterministic simulation, the ‘tau‑leaping’ method is used to:
Accelerate deterministic ODE integration
Approximate many reaction events over a time step τ, reducing computational cost while retaining stochasticity
Perform exact Gillespie steps
Compute eigenvalues of the Jacobian
Explanation - Tau‑leaping groups multiple reactions into a single leap, trading exactness for speed.
Correct answer is: Approximate many reaction events over a time step τ, reducing computational cost while retaining stochasticity
Q.69 When converting a biochemical reaction network into an electrical circuit analog, the law of conservation of charge corresponds to:
Conservation of mass (mass balance) in the biochemical system
Conservation of energy
Conservation of momentum
Conservation of voltage
Explanation - Kirchhoff’s current law (charge conservation) maps to mass balance: total inflow equals total outflow for each species.
Correct answer is: Conservation of mass (mass balance) in the biochemical system
Q.70 The term ‘elasticity’ in metabolic control analysis quantifies:
The ratio of fractional change in reaction rate to fractional change in substrate concentration
The physical stretchability of a cell membrane
The electrical capacitance of a pathway
The stochastic variance of a reaction
Explanation - Elasticity coefficients describe how sensitive a reaction rate is to changes in metabolite concentrations.
Correct answer is: The ratio of fractional change in reaction rate to fractional change in substrate concentration
Q.71 Which of the following is a typical feature of a ‘delay differential equation’ (DDE) compared to an ordinary differential equation (ODE)?
It includes terms that depend on past values of the state variables
It can only be solved analytically
It has no steady‑state solutions
It models spatial diffusion directly
Explanation - DDEs incorporate explicit time delays, e.g., x(t‑τ), reflecting processes with finite lag.
Correct answer is: It includes terms that depend on past values of the state variables
Q.72 In a model of a neuronal network that uses Hodgkin‑Huxley dynamics, the gating variables (m, h, n) are typically modeled using:
Algebraic equations only
First‑order ODEs describing voltage‑dependent rates
Partial differential equations
Boolean logic
Explanation - Gating variables follow kinetic equations with voltage‑dependent opening and closing rates.
Correct answer is: First‑order ODEs describing voltage‑dependent rates
Q.73 When using a ‘Latin Hypercube Sampling’ (LHS) scheme for parameter exploration, the main advantage is:
Ensuring each parameter range is sampled uniformly while requiring relatively few samples
Providing exact solutions to the model
Eliminating the need for stochastic simulations
Guaranteeing convergence to the global optimum
Explanation - LHS stratifies each parameter's range into intervals, improving coverage compared to simple random sampling.
Correct answer is: Ensuring each parameter range is sampled uniformly while requiring relatively few samples
Q.74 In the context of synthetic biology, a ‘ribosome binding site’ (RBS) strength primarily influences:
Transcription initiation rate
Translation initiation rate (protein synthesis rate)
mRNA degradation rate
DNA replication speed
Explanation - RBS determines how efficiently ribosomes bind to mRNA, controlling protein production levels.
Correct answer is: Translation initiation rate (protein synthesis rate)
Q.75 Which method would you use to test whether a simulated oscillatory behavior is due to a Hopf bifurcation?
Check for a pair of complex conjugate eigenvalues crossing the imaginary axis as a parameter varies
Compute the steady‑state flux balance
Perform a Monte Carlo simulation
Apply the Laplace transform
Explanation - A Hopf bifurcation occurs when a pair of eigenvalues moves from the left to the right half‑plane, creating a limit cycle.
Correct answer is: Check for a pair of complex conjugate eigenvalues crossing the imaginary axis as a parameter varies
Q.76 In a stochastic model, the term ‘propensity function’ a_i(x) denotes:
The deterministic rate constant of reaction i
The probability per unit time that reaction i occurs given state x
The electrical resistance of reaction i
The concentration of species i
Explanation - Propensity combines the kinetic rate constant with the number of possible reactant combinations in the current state.
Correct answer is: The probability per unit time that reaction i occurs given state x
Q.77 When a model includes an ‘allosteric inhibitor’, the kinetic effect is typically represented by:
A decrease in Vmax without affecting Km
A change in Km (apparent affinity) while Vmax remains unchanged (non‑competitive inhibition)
An increase in both Vmax and Km
No change in kinetic parameters
Explanation - Allosteric (non‑competitive) inhibition reduces effective affinity, altering Km but not Vmax.
Correct answer is: A change in Km (apparent affinity) while Vmax remains unchanged (non‑competitive inhibition)
Q.78 Which of the following is a direct consequence of violating the well‑mixed assumption in a stochastic simulation?
The Gillespie algorithm will produce exact results
Spatial heterogeneity can lead to inaccurate reaction propensities
The ODE model will become stiff
The model will automatically become deterministic
Explanation - Gillespie assumes all molecules are uniformly distributed; when this is false, the calculated propensities no longer reflect true reaction rates.
Correct answer is: Spatial heterogeneity can lead to inaccurate reaction propensities
Q.79 In the context of control theory applied to biological circuits, the ‘transfer function’ of a gene promoter describes:
The relationship between input transcription factor concentration and output mRNA production rate in the frequency domain
The DNA sequence of the promoter
The electrical resistance of the promoter
The stochastic variance of gene expression
Explanation - A transfer function captures how a promoter filters and amplifies signals, analogous to electrical systems.
Correct answer is: The relationship between input transcription factor concentration and output mRNA production rate in the frequency domain
Q.80 When a model exhibits ‘parameter sloppiness’, which of the following strategies can improve parameter identifiability?
Collect more informative experimental data that specifically perturb the sloppy directions
Reduce the number of parameters arbitrarily
Increase the simulation time step
Add random noise to the data
Explanation - Targeted experiments that excite sensitive modes can reduce uncertainty and break parameter sloppiness.
Correct answer is: Collect more informative experimental data that specifically perturb the sloppy directions
Q.81 In a deterministic model of a signaling cascade, the term ‘ultrasensitivity’ refers to:
A linear input‑output relationship
A highly cooperative, switch‑like response where a small change in input produces a large change in output
A random fluctuation in signal strength
A constant output regardless of input
Explanation - Ultrasensitivity often arises from multistep cascades or cooperative binding, leading to steep response curves.
Correct answer is: A highly cooperative, switch‑like response where a small change in input produces a large change in output
Q.82 Which of the following best describes the ‘curse of dimensionality’ in model parameter space exploration?
The difficulty of solving ODEs for large systems
The exponential growth of required sample points as the number of parameters increases
The inability to model electrical circuits
The reduction of model accuracy with more compartments
Explanation - High‑dimensional spaces require vastly more points to achieve the same coverage, making exhaustive sampling infeasible.
Correct answer is: The exponential growth of required sample points as the number of parameters increases
Q.83 In the context of synthetic biology design automation, a ‘part’ in the Registry of Standard Biological Parts usually corresponds to:
A DNA sequence with a defined functional role (e.g., promoter, RBS, coding sequence)
An electrical resistor
A mathematical equation
A stochastic simulation algorithm
Explanation - Standard Biological Parts are modular DNA elements that can be assembled to build circuits.
Correct answer is: A DNA sequence with a defined functional role (e.g., promoter, RBS, coding sequence)
Q.84 When applying the ‘Method of Moments’ to approximate a stochastic model, the approach:
Derives differential equations for the means, variances, and higher‑order moments of species counts
Simulates each reaction event exactly
Transforms the model into the frequency domain
Uses Boolean logic to simplify the network
Explanation - Moment equations provide deterministic approximations of stochastic dynamics, capturing mean and variability.
Correct answer is: Derives differential equations for the means, variances, and higher‑order moments of species counts
Q.85 Which of the following statements about the ‘Hill equation’ is FALSE?
When the Hill coefficient n > 1, the response curve is sigmoidal
The Hill equation can model cooperative binding
A Hill coefficient of 0.5 indicates negative cooperativity
The Hill equation always predicts a linear response
Explanation - The Hill equation produces non‑linear (often sigmoidal) curves; only n = 1 yields a hyperbolic (Michaelis–Menten) shape.
Correct answer is: The Hill equation always predicts a linear response
Q.86 In a model that uses ‘mass action kinetics’, the rate constant k has units that depend on:
The number of reactants involved in the reaction
The temperature only
The pH of the solution
The electrical voltage
Explanation - For a reaction A + B → C, k has units of concentration⁻¹·time⁻¹; for a unimolecular reaction, units are time⁻¹.
Correct answer is: The number of reactants involved in the reaction
Q.87 When analyzing a model with the software COPASI, the ‘Time‑course’ simulation type corresponds to:
A deterministic ODE integration over a specified time span
A steady‑state analysis only
A stochastic simulation using the Gillespie algorithm
A sensitivity analysis
Explanation - COPASI’s Time‑course task solves the model equations over time, producing trajectories for each species.
Correct answer is: A deterministic ODE integration over a specified time span
Q.88 In an electrical analogue of a calcium signaling pathway, the ion channel conductance can be represented by:
A resistor
A capacitor
An inductor
A voltage source
Explanation - Conductance (inverse of resistance) determines current flow, analogous to ion flux through a channel.
Correct answer is: A resistor
Q.89 Which of the following is a typical characteristic of a ‘bistable’ system?
Only one stable steady state for any parameter set
Two distinct stable steady states separated by an unstable one
Continuous oscillations for all initial conditions
No dependence on initial conditions
Explanation - Bistability allows the system to reside in either of two stable configurations, with a threshold separating them.
Correct answer is: Two distinct stable steady states separated by an unstable one
Q.90 When fitting a model to noisy experimental data, adding a regularization term (e.g., L2 penalty) to the cost function helps to:
Increase the number of parameters
Prevent over‑fitting by penalizing large parameter values
Make the optimization problem non‑convex
Eliminate the need for experimental replicates
Explanation - Regularization discourages extreme parameter values, improving generalization to unseen data.
Correct answer is: Prevent over‑fitting by penalizing large parameter values
Q.91 The term ‘phase resetting curve’ (PRC) is used to describe:
How a periodic oscillator’s phase shifts in response to a brief perturbation
The steady‑state concentration of a metabolite
The voltage‑current relationship in a resistor
The diffusion coefficient of a molecule
Explanation - PRCs are key for understanding synchronization and entrainment of biological rhythms.
Correct answer is: How a periodic oscillator’s phase shifts in response to a brief perturbation
Q.92 In a Boolean model, the update scheme that evaluates all nodes simultaneously at each discrete time step is called:
Synchronous updating
Asynchronous updating
Stochastic updating
Continuous updating
Explanation - All variables are updated in lock‑step, which can lead to artifacts not present in asynchronous or stochastic updates.
Correct answer is: Synchronous updating
Q.93 A model that includes both transcriptional regulation and metabolic feedback is an example of:
A purely electrical circuit
A multi‑scale, integrated systems biology model
A Boolean network only
A simple linear ODE
Explanation - Combining gene regulation (slow) with metabolism (fast) creates a multi‑scale network requiring careful coupling.
Correct answer is: A multi‑scale, integrated systems biology model
Q.94 Which of the following is NOT a typical assumption of the Michaelis–Menten derivation?
Enzyme concentration is much lower than substrate concentration
The formation of ES complex reaches a quasi‑steady state
Product inhibition is negligible
Substrate concentration is zero
Explanation - Michaelis–Menten assumes substrate is present; zero substrate would give zero reaction rate.
Correct answer is: Substrate concentration is zero
Q.95 When performing a ‘global optimization’ of model parameters, a common stopping criterion is:
Reaching a predefined number of iterations without improvement
Achieving a zero gradient at every point
Ensuring all parameters are integers
Running the algorithm for exactly one second
Explanation - Optimization may stop when the best objective value has not improved over several consecutive iterations.
Correct answer is: Reaching a predefined number of iterations without improvement
Q.96 In a kinetic model of enzyme inhibition, a competitive inhibitor affects:
Vmax only
Km only (apparent increase) while Vmax remains unchanged
Both Vmax and Km equally
Neither Vmax nor Km
Explanation - Competitive inhibitors compete with substrate for the active site, increasing the apparent Km.
Correct answer is: Km only (apparent increase) while Vmax remains unchanged
Q.97 When using a ‘particle filter’ for state estimation in a stochastic biological model, the particles represent:
Deterministic trajectories only
Samples of possible system states (e.g., concentrations) that are weighted according to their likelihood given observations
Electrical charges in a circuit
Boolean truth values
Explanation - Particle filters approximate the posterior distribution of hidden states using a set of weighted samples.
Correct answer is: Samples of possible system states (e.g., concentrations) that are weighted according to their likelihood given observations
Q.98 In a gene circuit modeled with ODEs, the term ‘leakiness’ of a promoter refers to:
Complete shutdown of transcription
A non‑zero basal transcription rate even in the absence of activators
Infinite transcription rate
A stochastic burst of transcription
Explanation - Leakiness captures unintended low‑level expression, influencing circuit performance.
Correct answer is: A non‑zero basal transcription rate even in the absence of activators
Q.99 Which of the following is a key advantage of using a ‘modular’ modeling framework (e.g., CellDesigner, BioModels) for systems biology?
It forces all models to be linear
It allows individual sub‑models to be developed, tested, and reused independently
It eliminates the need for parameter estimation
It guarantees that the model will be biologically accurate
Explanation - Modularity promotes reusability, easier debugging, and collaborative development.
Correct answer is: It allows individual sub‑models to be developed, tested, and reused independently
Q.100 When applying ‘principal component analysis’ (PCA) to a set of model simulation outputs, the main purpose is to:
Reduce dimensionality and identify dominant patterns in the data
Solve the ODEs analytically
Increase the number of parameters
Convert stochastic simulations into deterministic ones
Explanation - PCA projects high‑dimensional data onto orthogonal axes that capture the most variance.
Correct answer is: Reduce dimensionality and identify dominant patterns in the data
Q.101 In a deterministic model of a biochemical network, the term ‘nullcline’ refers to:
A curve where the derivative of one state variable is zero
A line of maximum voltage
A stochastic trajectory
A region where all reactions are paused
Explanation - Nullclines help locate steady states by indicating where each variable’s rate of change is zero.
Correct answer is: A curve where the derivative of one state variable is zero
Q.102 Which of the following statements about the ‘law of mass action’ is correct for a bimolecular reaction A + B → C?
Rate = k·[A]·[B]
Rate = k·[A] + [B]
Rate = k·[A]^2·[B]
Rate = k·[C]
Explanation - For a bimolecular reaction, the reaction rate is proportional to the product of the reactant concentrations.
Correct answer is: Rate = k·[A]·[B]
Q.103 In the context of synthetic biology, a ‘chassis’ cell refers to:
The DNA plasmid backbone
The host organism that provides the cellular environment for the engineered circuit
A type of resistor in an electrical analogue
A stochastic simulation algorithm
Explanation - The chassis supplies the metabolic and regulatory context in which parts operate.
Correct answer is: The host organism that provides the cellular environment for the engineered circuit
Q.104 When using the ‘Euler method’ to integrate stiff ODEs, a common problem is:
The method becomes unstable unless an extremely small time step is used
The method automatically solves the stiff problem
The method provides exact solutions
The method cannot be applied to biochemical systems
Explanation - Explicit Euler is conditionally stable; stiff systems require implicit methods or very small steps.
Correct answer is: The method becomes unstable unless an extremely small time step is used
Q.105 In a model that includes transcriptional regulation by a repressor, the repression can be mathematically modeled using:
A Hill function with negative exponent
A linear term proportional to repressor concentration
An exponential decay term
A constant term only
Explanation - Repression is often represented by an inhibitory Hill function: rate = Vmax/(1 + (R/K)^n).
Correct answer is: A Hill function with negative exponent
Q.106 Which of the following best describes the purpose of a ‘sensitivity heatmap’ in model analysis?
To display the magnitude of sensitivity coefficients for many parameters and outputs in a single visual matrix
To solve ODEs faster
To measure electrical resistance
To generate random numbers
Explanation - Heatmaps provide an at‑a‑glance view of which parameters most affect which model outputs.
Correct answer is: To display the magnitude of sensitivity coefficients for many parameters and outputs in a single visual matrix
Q.107 When a model exhibits ‘limit cycle oscillations’, the period of the oscillation is:
Infinite
Zero
Constant (independent of initial conditions, once the limit cycle is reached)
Random
Explanation - A limit cycle has a fixed period and amplitude, attracting nearby trajectories regardless of starting point.
Correct answer is: Constant (independent of initial conditions, once the limit cycle is reached)
Q.108 In a stochastic simulation, the ‘Gillespie direct method’ differs from the ‘first‑reaction method’ primarily in:
How reaction times are sampled (direct method samples one reaction per step; first‑reaction samples all and picks the earliest)
The type of differential equations used
The requirement for a well‑mixed system
Its ability to handle deterministic systems
Explanation - Both are exact SSA variants; the direct method chooses a reaction and its time together, while the first‑reaction method computes tentative times for all reactions.
Correct answer is: How reaction times are sampled (direct method samples one reaction per step; first‑reaction samples all and picks the earliest)
Q.109 When a model includes a ‘feed‑forward loop’ with an AND logic gate, the output response typically shows:
Immediate activation without delay
A delayed and sharpened response, filtering short input pulses
No response at all
Random fluctuations
Explanation - Coherent FFLs with AND logic act as sign‑sensitive filters, requiring sustained input to produce output.
Correct answer is: A delayed and sharpened response, filtering short input pulses
Q.110 In a deterministic model, the term ‘steady‑state flux balance analysis’ (FBA) assumes:
All species concentrations change linearly over time
The system is at steady state, so the net production/consumption of each internal metabolite is zero
All reactions are stochastic
All parameters are time‑dependent
Explanation - FBA solves a linear programming problem under the steady‑state assumption S·v = 0.
Correct answer is: The system is at steady state, so the net production/consumption of each internal metabolite is zero
Q.111 The ‘Morris method’ for global sensitivity analysis is particularly useful because:
It requires only a few model evaluations to estimate elementary effects
It gives exact Sobol indices
It works only for linear models
It eliminates the need for any sampling
Explanation - Morris is a screening method that efficiently identifies important parameters with modest computational cost.
Correct answer is: It requires only a few model evaluations to estimate elementary effects
Q.112 Which of the following statements about ‘parameter identifiability’ is true?
If two parameters appear only as a product in the model equations, they are structurally identifiable individually
Structural identifiability depends only on model structure, not on data
Identifiability is unrelated to the experimental design
All parameters are always identifiable if the model has enough equations
Explanation - Structural identifiability assesses whether unique parameter values can be inferred from perfect noise‑free data given the model equations.
Correct answer is: Structural identifiability depends only on model structure, not on data
Q.113 In an electrical analogue, a series R‑C circuit has a characteristic time constant τ = RC. In the corresponding biochemical analogue, τ most directly represents:
The half‑life of a metabolite under first‑order degradation
The diffusion coefficient of a substrate
The binding affinity of a transcription factor
The number of genes in the network
Explanation - RC time constant dictates exponential decay; analogously, degradation rate k leads to τ = 1/k (half‑life ≈ ln2/k).
Correct answer is: The half‑life of a metabolite under first‑order degradation
Q.114 When using a ‘Kalman filter’ for state estimation in a linear stochastic model, the filter assumes that:
Process and observation noises are Gaussian and the system dynamics are linear
All variables are deterministic
Noise follows a Poisson distribution
The system is nonlinear and chaotic
Explanation - Kalman filter provides optimal linear‑Gaussian estimation; extensions (EKF, UKF) handle nonlinearity.
Correct answer is: Process and observation noises are Gaussian and the system dynamics are linear
Q.115 In a model of quorum sensing, the extracellular concentration of autoinducer is typically modeled using:
A diffusion term coupling the intracellular production to the extracellular space
A Boolean variable only
An invariant constant
A pure degradation term without production
Explanation - Autoinducer is synthesized inside cells and diffuses out, requiring transport terms between compartments.
Correct answer is: A diffusion term coupling the intracellular production to the extracellular space
Q.116 The ‘Hill coefficient’ n in a cooperative binding curve determines:
The maximum possible concentration of the ligand
The steepness (cooperativity) of the response curve
The temperature dependence of binding
The electrical resistance of the system
Explanation - Higher n yields a sharper transition between low and high occupancy, reflecting stronger cooperativity.
Correct answer is: The steepness (cooperativity) of the response curve
Q.117 When performing ‘parameter sweep’ studies, the term ‘bifurcation diagram’ is often generated by:
Plotting steady‑state values of a variable versus the varied parameter
Plotting time‑course trajectories for a single parameter set
Computing the Laplace transform of the model
Measuring electrical voltage
Explanation - Bifurcation diagrams reveal how equilibria appear/disappear or change stability as a control parameter changes.
Correct answer is: Plotting steady‑state values of a variable versus the varied parameter
Q.118 In a stochastic model, the ‘mean‑field approximation’ replaces the stochastic dynamics with:
Deterministic ODEs for the average concentrations
Exact Gillespie trajectories
Boolean logic
Random number generation only
Explanation - Mean‑field assumes that the average behavior approximates the stochastic system, neglecting fluctuations.
Correct answer is: Deterministic ODEs for the average concentrations
Q.119 A common metric to quantify the similarity between two time‑course simulations is:
Pearson correlation coefficient
Ohm’s law
Laplace transform magnitude
Boolean equivalence
Explanation - Correlation measures linear similarity between two temporal profiles, useful for comparing model outputs.
Correct answer is: Pearson correlation coefficient
Q.120 When a model includes an enzymatic step with ‘product inhibition’, the rate law typically contains:
An inhibitory term in the denominator that depends on product concentration
Only the substrate concentration
A constant rate independent of concentrations
A term proportional to temperature only
Explanation - Product inhibition reduces the effective rate as product builds up, often modeled as Vmax/(1 + [P]/K_i).
Correct answer is: An inhibitory term in the denominator that depends on product concentration
Q.121 Which of the following is a characteristic feature of a ‘deterministic chaos’ attractor?
A single fixed point
A strange attractor with a fractal structure
A perfect sinusoidal oscillation
A linear trajectory
Explanation - Chaotic systems settle onto strange attractors that are bounded but non‑periodic and have fractal geometry.
Correct answer is: A strange attractor with a fractal structure