25,258 research outputs found
Systems approaches and algorithms for discovery of combinatorial therapies
Effective therapy of complex diseases requires control of highly non-linear
complex networks that remain incompletely characterized. In particular, drug
intervention can be seen as control of signaling in cellular networks.
Identification of control parameters presents an extreme challenge due to the
combinatorial explosion of control possibilities in combination therapy and to
the incomplete knowledge of the systems biology of cells. In this review paper
we describe the main current and proposed approaches to the design of
combinatorial therapies, including the empirical methods used now by clinicians
and alternative approaches suggested recently by several authors. New
approaches for designing combinations arising from systems biology are
described. We discuss in special detail the design of algorithms that identify
optimal control parameters in cellular networks based on a quantitative
characterization of control landscapes, maximizing utilization of incomplete
knowledge of the state and structure of intracellular networks. The use of new
technology for high-throughput measurements is key to these new approaches to
combination therapy and essential for the characterization of control
landscapes and implementation of the algorithms. Combinatorial optimization in
medical therapy is also compared with the combinatorial optimization of
engineering and materials science and similarities and differences are
delineated.Comment: 25 page
Natural evolution strategies and variational Monte Carlo
A notion of quantum natural evolution strategies is introduced, which
provides a geometric synthesis of a number of known quantum/classical
algorithms for performing classical black-box optimization. Recent work of
Gomes et al. [2019] on heuristic combinatorial optimization using neural
quantum states is pedagogically reviewed in this context, emphasizing the
connection with natural evolution strategies. The algorithmic framework is
illustrated for approximate combinatorial optimization problems, and a
systematic strategy is found for improving the approximation ratios. In
particular it is found that natural evolution strategies can achieve
approximation ratios competitive with widely used heuristic algorithms for
Max-Cut, at the expense of increased computation time
Fast Quantum Methods for Optimization
Discrete combinatorial optimization consists in finding the optimal
configuration that minimizes a given discrete objective function. An
interpretation of such a function as the energy of a classical system allows us
to reduce the optimization problem into the preparation of a low-temperature
thermal state of the system. Motivated by the quantum annealing method, we
present three strategies to prepare the low-temperature state that exploit
quantum mechanics in remarkable ways. We focus on implementations without
uncontrolled errors induced by the environment. This allows us to rigorously
prove a quantum advantage. The first strategy uses a classical-to-quantum
mapping, where the equilibrium properties of a classical system in spatial
dimensions can be determined from the ground state properties of a quantum
system also in spatial dimensions. We show how such a ground state can be
prepared by means of quantum annealing, including quantum adiabatic evolutions.
This mapping also allows us to unveil some fundamental relations between
simulated and quantum annealing. The second strategy builds upon the first one
and introduces a technique called spectral gap amplification to reduce the time
required to prepare the same quantum state adiabatically. If implemented on a
quantum device that exploits quantum coherence, this strategy leads to a
quadratic improvement in complexity over the well-known bound of the classical
simulated annealing method. The third strategy is not purely adiabatic;
instead, it exploits diabatic processes between the low-energy states of the
corresponding quantum system. For some problems it results in an exponential
speedup (in the oracle model) over the best classical algorithms.Comment: 15 pages (2 figures
Multiobjective strategies for New Product Development in the pharmaceutical industry
New Product Development (NPD) constitutes a challenging problem in the pharmaceutical industry, due to the characteristics of the development pipeline. Formally, the NPD problem can be stated as follows: select a set of R&D projects from a pool of candidate projects in order to satisfy several criteria (economic profitability, time to market) while coping with the uncertain nature of the projects. More precisely, the recurrent key issues are to determine the projects to develop once target molecules have been identified, their order and the level of resources to assign. In this context, the proposed approach combines discrete event stochastic simulation (Monte Carlo approach) with multiobjective genetic algorithms (NSGAII type, Non-Sorted Genetic Algorithm II) to optimize the highly combinatorial portfolio management problem. In that context, Genetic Algorithms (GAs) are particularly attractive for treating this kind of problem, due to their ability to directly lead to the so-called Pareto front and to account for the combinatorial aspect. This work is illustrated with a study case involving nine interdependent new product candidates targeting three diseases. An analysis is performed for this test bench on the different pairs of criteria both for the bi- and tricriteria optimization: large portfolios cause resource queues and delays time to launch and are eliminated by the bi- and tricriteria optimization strategy. The optimization strategy is thus interesting to detect the sequence candidates. Time is an important criterion to consider simultaneously with NPV and risk criteria. The order in which drugs are released in the pipeline is of great importance as with scheduling problems
Multiobjective strategies for New Product Development in the pharmaceutical industry
New Product Development (NPD) constitutes a challenging problem in the pharmaceutical industry, due to the characteristics of the development pipeline. Formally, the NPD problem can be stated as follows: select a set of R&D projects from a pool of candidate projects in order to satisfy several criteria (economic profitability, time to market) while coping with the uncertain nature of the projects. More precisely, the recurrent key issues are to determine the projects to develop once target molecules have been identified, their order and the level of resources to assign. In this context, the proposed approach combines discrete event stochastic simulation (Monte Carlo approach) with multiobjective genetic algorithms (NSGAII type, Non-Sorted Genetic Algorithm II) to optimize the highly combinatorial portfolio management problem. In that context, Genetic Algorithms (GAs) are particularly attractive for treating this kind of problem, due to their ability to directly lead to the so-called Pareto front and to account for the combinatorial aspect. This work is illustrated with a study case involving nine interdependent new product candidates targeting three diseases. An analysis is performed for this test bench on the different pairs of criteria both for the bi- and tricriteria optimization: large portfolios cause resource queues and delays time to launch and are eliminated by the bi- and tricriteria optimization strategy. The optimization strategy is thus interesting to detect the sequence candidates. Time is an important criterion to consider simultaneously with NPV and risk criteria. The order in which drugs are released in the pipeline is of great importance as with scheduling problems
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