FastKnock: an efficient next-generation approach to identify all knockout strategies for strain optimization.

Overproduction of desired native or nonnative biochemical(s) in (micro)organisms can be achieved through metabolic engineering. Appropriate rewiring of cell metabolism is performed by making rational changes such as insertion, up-/down-regulation and knockout of genes and consequently metabolic reactions. Finding appropriate targets (including proper sets of reactions to be knocked out) for metabolic engineering to design optimal production strains has been the goal of a number of computational algorithms. We developed FastKnock, an efficient next-generation algorithm for identifying all possible knockout strategies (with a predefined maximum number of reaction deletions) for the growth-coupled overproduction of biochemical(s) of interest. We achieve this by developing a special depth-first traversal algorithm that allows us to prune the search space significantly. This leads to a drastic reduction in execution time. We evaluate the performance of the FastKnock algorithm using various Escherichia coli genome-scale metabolic models in different conditions (minimal and rich mediums) for the overproduction of a number of desired metabolites. FastKnock efficiently prunes the search space to less than 0.2% for quadruple- and 0.02% for quintuple-reaction knockouts. Compared to the classic approaches such as OptKnock and the state-of-the-art techniques such as MCSEnumerator methods, FastKnock found many more beneficial and important practical solutions. The availability of all the solutions provides the opportunity to further characterize, rank and select the most appropriate intervention strategy based on any desired evaluation index. Our implementation of the FastKnock method in Python is publicly available at https://github.com/leilahsn/FastKnock .

An Environment-Aware Adaptive Data-Gathering Method for Packet-Level Index Modulation in LPWA.

Low-power wide-area (LPWA) is a communication technology for the IoT that allows low power consumption and long-range communication. Additionally, packet-level index modulation (PLIM) can transmit additional information using multiple frequency channels and time slots. However, in a competitive radio access environment, where multiple sensors autonomously determine packet transmission, packet collisions occur when transmitting the same information. The packet collisions cause a reduction in the throughput. A method has been proposed to design a mapping table that shows the correspondence between indexes and information using a packet collision minimization criterion. However, the effectiveness of this method depends on how the probability of the occurrence of the information to be transmitted is modeled. We propose an environment-aware adaptive data-gathering method that identifies the location of factors affecting sensor information and constructs a model for the probability of the occurrence of sensor information. The packet collision rate of the environment-aware adaptive data-gathering method was clarified through computer simulations and actual experiments on a 429 MHz LPWA. We confirm that the proposed scheme improves the packet collision rate by 15% in the computer simulation and 30% in the experimental evaluation, respectively.

SGRTmreg: A Learning-Based Optimization Framework for Multiple Pairwise Registrations.

Point cloud registration is a fundamental task in computer vision and graphics, which is widely used in 3D reconstruction, object tracking, and atlas reconstruction. Learning-based optimization and deep learning methods have been widely developed in pairwise registration due to their own distinctive advantages. Deep learning methods offer greater flexibility and enable registering unseen point clouds that are not trained. Learning-based optimization methods exhibit enhanced robustness and stability when handling registration under various perturbations, such as noise, outliers, and occlusions. To leverage the strengths of both approaches to achieve a less time-consuming, robust, and stable registration for multiple instances, we propose a novel computational framework called SGRTmreg for multiple pairwise registrations in this paper. The SGRTmreg framework utilizes three components-a Searching scheme, a learning-based optimization method called Graph-based Reweighted discriminative optimization (GRDO), and a Transfer module to achieve multi-instance point cloud registration.Given a collection of instances to be matched, a template as a target point cloud, and an instance as a source point cloud, the searching scheme selects one point cloud from the collection that closely resembles the source. GRDO then learns a sequence of regressors by aligning the source to the target, while the transfer module stores and applies the learned regressors to align the selected point cloud to the target and estimate the transformation of the selected point cloud. In short, SGRTmreg harnesses a shared sequence of regressors to register multiple point clouds to a target point cloud. We conduct extensive registration experiments on various datasets to evaluate the proposed framework. The experimental results demonstrate that SGRTmreg achieves multiple pairwise registrations with higher accuracy, robustness, and stability than the state-of-the-art deep learning and traditional registration methods.

Safe distancing in the time of COVID-19.

The spread of viruses such as SARS-CoV-2 brought new challenges to our society, including a stronger focus on safety across all businesses. Many countries have imposed a minimum social distance among people in order to ensure their safety. This brings new challenges to many customer-related businesses, such as restaurants, offices, theaters, etc., on how to locate their facilities (tables, seats etc.) under distancing constraints. We propose a parallel between this problem and that of locating wind turbines in an offshore area. The discovery of this parallel allows us to apply Mathematical Optimization algorithms originally designed for wind farms, to produce optimized facility layouts that minimize the overall risk of infection among customers. In this way we can investigate the structure of the safest layouts, with some surprising outcomes. A lesson learned is that, in the safest layouts, the facilities are not equally distanced (as it is typically believed) but tend to concentrate on the border of the available area-a policy that significantly reduces the overall risk of contagion.

Supply chain planning of vaccine and pharmaceutical clusters under uncertainty: The case of COVID-19.

As an abrupt epidemic occurs, healthcare systems are shocked by the surge in the number of susceptible patients' demands, and decision-makers mostly rely on their frame of reference for urgent decision-making. Many reports have declared the COVID-19 impediments to trading and global economic growth. This study aims to provide a mathematical model to support pharmaceutical supply chain planning during the COVID-19 epidemic. Additionally, it aims to offer new insights into hospital supply chain problems by unifying cold and non-cold chains and considering a wide range of pharmaceuticals and vaccines. This approach is unprecedented and includes an analysis of various pharmaceutical features such as temperature, shelf life, priority, and clustering. To propose a model for planning the pharmaceutical supply chains, a mixed-integer linear programming (MILP) model is used for a four-echelon supply chain design. This model aims to minimize the costs involved in the pharmaceutical supply chain by maintaining an acceptable service level. Also, this paper considers uncertainty as an intrinsic part of the problem and addresses it through the wait-and-see method. Furthermore, an unexplored unsupervised learning method in the realm of supply chain planning has been used to cluster the pharmaceuticals and the vaccines and its merits and drawbacks are proposed. A case of Tehran hospitals with real data has been used to show the model's capabilities, as well. Based on the obtained results, the proposed approach is able to reach the optimum service level in the COVID conditions while maintaining a reduced cost. The experiment illustrates that the hospitals' adjacency and emergency orders alleviated the service level significantly. The proposed MILP model has proven to be efficient in providing a practical intuition for decision-makers. The clustering technique reduced the size of the problem and the time required to solve the model considerably.

The potential effects of meat substitution on diet quality could be high if meat substitutes are optimized for nutritional composition-a modeling study in French adults (INCA3).

PURPOSE: While consumer demand for meat substitutes is growing, their varied composition raises questions regarding their nutritional value. We aimed to identify and characterize the optimal composition of a meat substitute that would best improve diet quality after complete meat replacement. METHODS: From an average individual representing the dietary intake of French adults (INCA3, n = 1125), meat was replaced with an equivalent amount of a mostly pulse-based substitute, whose composition was based on a list of 159 possible plant ingredients and optimized non-linearly to maximize diet quality assessed with the PANDiet score (considering adequacy for 32 nutrients), while taking account of technological constraints and applying nutritional constraints to limit the risk of overt deficiency in 12 key nutrients. RESULTS: The optimized meat substitute contained 13 minimally processed ingredients. When used to substitute meat, the PANDiet score increased by 5.7 points above its initial value before substitution (versus - 3.1 to + 1.5 points when using other substitutes on the market), mainly because of higher intakes of nutrients that are currently insufficiently consumed (e.g., alpha-linolenic acid, fiber, linoleic acid) and a lower SFA intake. The meat substitute also mostly compensated for the lower provision of some indispensable nutrients to which meat greatly contributed (e.g., vitamin B6, potassium, bioavailable iron), but it could not compensate for bioavailable zinc and vitamin B12. CONCLUSION: Choosing the correct ingredients can result in a nutritionally highly effective meat substitute that could compensate for reductions in many nutrients supplied by meat while providing key nutrients that are currently insufficiently consumed.

Optimal resource allocation in HIV self-testing secondary distribution among Chinese MSM: data-driven integer programming models.

Human immunodeficiency virus self-testing (HIVST) is an innovative and effective strategy important to the expansion of HIV testing coverage. Several innovative implementations of HIVST have been developed and piloted among some HIV high-risk populations like men who have sex with men (MSM) to meet the global testing target. One innovative strategy is the secondary distribution of HIVST, in which individuals (defined as indexes) were given multiple testing kits for both self-use (i.e.self-testing) and distribution to other people in their MSM social network (defined as alters). Studies about secondary HIVST distribution have mainly concentrated on developing new intervention approaches to further increase the effectiveness of this relatively new strategy from the perspective of traditional public health discipline. There are many points of HIVST secondary distribution in which mathematical modelling can play an important role. In this study, we considered secondary HIVST kits distribution in a resource-constrained situation and proposed two data-driven integer linear programming models to maximize the overall economic benefits of secondary HIVST kits distribution based on our present implementation data from Chinese MSM. The objective function took expansion of normal alters and detection of positive and newly-tested 'alters' into account. Based on solutions from solvers, we developed greedy algorithms to find final solutions for our linear programming models. Results showed that our proposed data-driven approach could improve the total health economic benefit of HIVST secondary distribution. This article is part of the theme issue 'Data science approaches to infectious disease surveillance'.

Decision-support systems for ambulatory care, including pandemic requirements: using mathematically optimized solutions.

BACKGROUND: The healthcare sector poses many strategic, tactic and operational planning questions. Due to the historically grown structures, planning is often locally confined and much optimization potential is foregone. METHODS: We implemented optimized decision-support systems for ambulatory care for four different real-world case studies that cover a variety of aspects in terms of planning scope and decision support tools. All are based on interactive cartographic representations and are being developed in cooperation with domain experts. The planning problems that we present are the problem of positioning centers for vaccination against Covid-19 (strategical) and emergency doctors (strategical/tactical), the out-of-hours pharmacy planning problem (tactical), and the route planning of patient transport services (operational). For each problem, we describe the planning question, give an overview of the mathematical model and present the implemented decision support application. RESULTS: Mathematical optimization can be used to model and solve these planning problems. However, in order to convince decision-makers of an alternative solution structure, mathematical solutions must be comprehensible and tangible. Appealing and interactive decision-support tools can be used in practice to convince public health experts of the benefits of an alternative solution. The more strategic the problem and the less sensitive the data, the easier it is to put a tool into practice. CONCLUSIONS: Exploring solutions interactively is rarely supported in existing planning tools. However, in order to bring new innovative tools into productive use, many hurdles must be overcome.

Bi-objective optimization of a stochastic resilient vaccine distribution network in the context of the COVID-19 pandemic.

This paper develops an approach to optimize a vaccine distribution network design through a mixed-integer nonlinear programming model with two objectives: minimizing the total expected number of deaths among the population and minimizing the total distribution cost of the vaccination campaign. Additionally, we assume that a set of input parameters (e.g., death rate, social contacts, vaccine supply, etc.) is uncertain, and the distribution network is exposed to disruptions. We then investigate the resilience of the distribution network through a scenario-based robust-stochastic optimization approach. The proposed model is linearized and finally validated through a real case study of the COVID-19 vaccination campaign in France. We show that the current vaccination strategies are not optimal, and vaccination prioritization among the population and the equity of vaccine distribution depend on other factors than those conceived by health policymakers. Furthermore, we demonstrate that a vaccination strategy mixing the population prioritization and the quarantine restrictions leads to an 8.5% decrease in the total number of deaths.

On sparse ensemble methods: An application to short-term predictions of the evolution of COVID-19.

Since the seminal paper by Bates and Granger in 1969, a vast number of ensemble methods that combine different base regressors to generate a unique one have been proposed in the literature. The so-obtained regressor method may have better accuracy than its components, but at the same time it may overfit, it may be distorted by base regressors with low accuracy, and it may be too complex to understand and explain. This paper proposes and studies a novel Mathematical Optimization model to build a sparse ensemble, which trades off the accuracy of the ensemble and the number of base regressors used. The latter is controlled by means of a regularization term that penalizes regressors with a poor individual performance. Our approach is flexible to incorporate desirable properties one may have on the ensemble, such as controlling the performance of the ensemble in critical groups of records, or the costs associated with the base regressors involved in the ensemble. We illustrate our approach with real data sets arising in the COVID-19 context.