Optimal HP configurations of proteins by combining local search with elastic net algorithm

The prediction of protein conformation from its amino-acid sequence is one of the most prominent problems in computational biology. But it is NP-hard. Here, we focus on an abstraction widely studied of this problem, the two-dimensional hydrophobic-polar protein folding problem (2D HP PFP). Mathematical optimal model of free energy of protein is established. Native conformations are often sought using stochastic sampling methods, but which are slow. The elastic net (EN) algorithm is one of fast deterministic methods as travelling salesman problem (TSP) strategies. However, it cannot be applied directly to protein folding problem, because of fundamental differences in the two types of problems. In this paper, how the 2D HP protein folding problem can be framed in terms of TSP is shown. Combination of the modified elastic net algorithm and novel local search method is adopted to solve this problem. To our knowledge, this is the first application of EN algorithm to 2D HP model. The results indicate that our approach can find more optimal conformations and is simple to implement, computationally efficient and fast.     

Optimal HP configurations of proteins by combining local search with elastic net algorithm

The prediction of protein conformation from its amino-acid sequence is one of the most prominent problems in computational biology. But it is NP-hard. Here, we focus on an abstraction widely studied of this problem, the two-dimensional hydrophobic-polar protein folding problem (2D HP PFP). Mathematical optimal model of free energy of protein is established. Native conformations are often sought using stochastic sampling methods, but which are slow. The elastic net (EN) algorithm is one of fast deterministic methods as travelling salesman problem (TSP) strategies. However, it cannot be applied directly to protein folding problem, because of fundamental differences in the two types of problems. In this paper, how the 2D HP protein folding problem can be framed in terms of TSP is shown. Combination of the modified elastic net algorithm and novel local search method is adopted to solve this problem. To our knowledge, this is the first application of EN algorithm to 2D HP model. The results indicate that our approach can find more optimal conformations and is simple to implement, computationally efficient and fast.     

People Efficiently Explore the Solution Space of the Computationally Intractable Traveling Salesman Problem to Find Near-Optimal Tours

Humans need to solve computationally intractable problems such as visual search, categorization, and simultaneous learning and acting, yet an increasing body of evidence suggests that their solutions to instantiations of these problems are near optimal. Computational complexity advances an explanation to this apparent paradox: (1) only a small portion of instances of such problems are actually hard, and (2) successful heuristics exploit structural properties of the typical instance to selectively improve parts that are likely to be sub-optimal. We hypothesize that these two ideas largely account for the good performance of humans on computationally hard problems. We tested part of this hypothesis by studying the solutions of 28 participants to 28 instances of the Euclidean Traveling Salesman Problem (TSP). Participants were provided feedback on the cost of their solutions and were allowed unlimited solution attempts (trials). We found a significant improvement between the first and last trials and that solutions are significantly different from random tours that follow the convex hull and do not have self-crossings. More importantly, we found that participants modified their current better solutions in such a way that edges belonging to the optimal solution (“good” edges) were significantly more likely to stay than other edges (“bad” edges), a hallmark of structural exploitation. We found, however, that more trials harmed the participants'' ability to tell good from bad edges, suggesting that after too many trials the participants “ran out of ideas.” In sum, we provide the first demonstration of significant performance improvement on the TSP under repetition and feedback and evidence that human problem-solving may exploit the structure of hard problems paralleling behavior of state-of-the-art heuristics.     

A neural network algorithm for the multiple traveling salesmen problem

We developed an efficient neural network algorithm for solving the Multiple Traveling Salesmen Problem (MTSP). A new transformation of the N-city M-salesmen MTSP to the standard Traveling Salesmen Problem (TSP) is introduced. The transformed problem is represented by an expanded version of Hopfield-Tank's neuromorphic city-position map with (N + M-1)-cities and a single fictitious salesmen. The dynamic model associated with the problem is based on the Basic Differential Multiplier Method (BDMM) [26] which evaluates Lagrange multipliers simultaneously with the problem's state variables. The algorithm was successfully tested on many problems with up to 30 cities and five salesmen. In all test cases, the algorithm always converged to valid solutions. The great advantage of this kind of algorithm is that it can provide solutions to complex decision making problems directly by solving a system of ordinary differential equations. No learning steps, logical if statements or adjusting of parameters are required during the computation. The algorithm can therefore be implemented in hardware to solve complex constraint satisfaction problems such as the MTSP at the speed of analog silicon VLSI devices or possibly future optical neural computers.     

Using traveling salesman problem algorithms for evolutionary tree construction

MOTIVATION: The construction of evolutionary trees is one of the major problems in computational biology, mainly due to its complexity. RESULTS: We present a new tree construction method that constructs a tree with minimum score for a given set of sequences, where the score is the amount of evolution measured in PAM distances. To do this, the problem of tree construction is reduced to the Traveling Salesman Problem (TSP). The input for the TSP algorithm are the pairwise distances of the sequences and the output is a circular tour through the optimal, unknown tree plus the minimum score of the tree. The circular order and the score can be used to construct the topology of the optimal tree. Our method can be used for any scoring function that correlates to the amount of changes along the branches of an evolutionary tree, for instance it could also be used for parsimony scores, but it cannot be used for least squares fit of distances. A TSP solution reduces the space of all possible trees to 2n. Using this order, we can guarantee that we reconstruct a correct evolutionary tree if the absolute value of the error for each distance measurement is smaller than f2.gif" BORDER="0">, where f3.gif" BORDER="0">is the length of the shortest edge in the tree. For data sets with large errors, a dynamic programming approach is used to reconstruct the tree. Finally simulations and experiments with real data are shown.     

A semi-localized elastic net for surface reconstruction of objects from multislice images

The traveling salesman problem (TSP) is a prototypical problem of combinatorial optimization and, as such, it has received considerable attention from neural-network researchers seeking quick, heuristic solutions. An early stage in many computer vision tasks is the extraction of object shape from an image consisting of noisy candidate edge points. Since the desired shape will often be a closed contour, this problem can be viewed as a version of the TSP in which we wish to link only a subset of the points/cities (i.e. the "noisefree" ones). None of the extant neural techniques for solving the TSP can deal directly with this case. In this paper, we present a simple but effective modification to the (analog) elastic net of Durbin and Willshaw which shifts emphasis from global to local behavior during convergence, so allowing the net to ignore some image points. Unlike the original elastic net, this semi-localized version is shown to tolerate considerable amounts of noise. As an example practical application, we describe the extraction of "pseudo-3D" human lung outlines from multiple preprocessed magnetic resonance images of the torso. An effectiveness measure (ideally zero) quantifies the difference between the extracted shape and some idealized shape exemplar. Our method produces average effectiveness scores of 0.06 for lung shapes extracted from initial semi-automatic segmentations which define the noisefree case. This deteriorates to 0.1 when extraction is from a noisy edge-point image obtained fully-automatically using a feedforward neural network.     

Probabilistic computation by neuromine networks

In this paper, we address the question, can biologically feasible neural nets compute more than can be computed by deterministic polynomial time algorithms? Since we want to maintain a claim of plausibility and reasonableness we restrict ourselves to algorithmically easy to construct nets and we rule out infinite precision in parameters and in any analog parts of the computation. Our approach is to consider the recent advances in randomized algorithms and see if such randomized computations can be described by neural nets. We start with a pair of neurons and show that by connecting them with reciprocal inhibition and some tonic input, then the steady-state will be one neuron ON and one neuron OFF, but which neuron will be ON and which neuron will be OFF will be chosen at random (perhaps, it would be better to say that microscopic noise in the analog computation will be turned into a megascale random bit). We then show that we can build a small network that uses this random bit process to generate repeatedly random bits. This random bit generator can then be connected with a neural net representing the deterministic part of randomized algorithm. We, therefore, demonstrate that these neural nets can carry out probabilistic computation and thus be less limited than classical neural nets.     

A canonical form for neural nets without circles

By “neural net” will be meant “neural net without circles.” Every neural net effects a transformation from inputs (i.e., firing patterns of the input neurons) to outputs (firing patterns of the output neurons). Two neural nets will be calledequivalent if they effect the same transformation from inputs to outputs. A canonical form is found for neural nets with respect to equivalence; i.e., a class of neural nets is defined, no two of which are equivalent, and which contains a neural net equivalent to any given neural net. This research was supported by the U.S. Air Force under Contract AF 49(638)-414 monitored by the Air Force Office of Scientific Research.     

Responses of recurrent nets of asymmetric ON and OFF cells

A neural field model of ON and OFF cells with all-to-all inhibitory feedback is investigated. External spatiotemporal stimuli drive the ON and OFF cells with, respectively, direct and inverted polarity. The dynamic differences between networks built of ON and OFF cells (“ON/OFF”) and those having only ON cells (“ON/ON”) are described for the general case where ON and OFF cells can have different spontaneous firing rates; this asymmetric case is generic. Neural responses to nonhomogeneous static and time-periodic inputs are analyzed in regimes close to and away from self-oscillation. Static stimuli can cause oscillatory behavior for certain asymmetry levels. Time-periodic stimuli expose dynamical differences between ON/OFF and ON/ON nets. Outside the stimulated region, we show that ON/OFF nets exhibit frequency doubling, while ON/ON nets cannot. On the other hand, ON/ON networks show antiphase responses between stimulated and unstimulated regions, an effect that does not rely on specific receptive field circuitry. An analysis of the resonance properties of both net types reveals that ON/OFF nets exhibit larger response amplitude. Numerical simulations of the neural field models agree with theoretical predictions for localized static and time-periodic forcing. This is also the case for simulations of a network of noisy integrate-and-fire neurons. We finally discuss the application of the model to the electrosensory system and to frequency-doubling effects in retina.     

A neural net model for multiple memory domains

Previous studies with neural nets constructed of discrete populations of formal neurons have assumed that all neurons have the same probability of connection with any other neuron in the net. However, in this new study we incorporate the behavior of the neural systems in which the neural connections can be set up by means of chemical markers carried by the individual cells. With this new approach we studied the dynamics of isolated neural nets again as well as the dynamics of neural nets with sustained inputs. Results obtained with this approach show simple and multiple hysteresis phenomena. Such hysteresis loops may be considered to represent the basis for short-term memory.     

Stability analysis of higher-order neural networks for combinatorial optimization

Recurrent neural networks with higher order connections, from here on referred to as higher-order neural networks (HONNs), may be used for the solution of combinatorial optimization problems. In Ref. 5 a mapping of the traveling salesman problem (TSP) onto a HONN of arbitrary order was developed, thereby creating a family of related networks that can be used to solve the TSP. In this paper, we explore the trade-off between network complexity and quality of solution that is made available by the HONN mapping of the TSP. The trade-off is investigated by undertaking an analysis of the stability of valid solutions to the TSP in a HONN of arbitrary order. The techniques used to perform the stability analysis are not new, but have been widely used elsewhere in the literature. The original contribution in this paper is the application of these techniques to a HONN of arbitrary order used to solve the TSP. The results of the stability analysis show that the quality of solution is improved by increasing the network complexity, as measured by the order of the network. Furthermore, it is shown that the Hopfield network, as the simplest network in the family of higher-order networks, is expected to produce the poorest quality of solution.     

Least-squares methods for blind source separation based on nonlinear PCA

In standard blind source separation, one tries to extract unknown source signals from their instantaneous linear mixtures by using a minimum of a priori information. We have recently shown that certain nonlinear extensions of principal component type neural algorithms can be successfully applied to this problem. In this paper, we show that a nonlinear PCA criterion can be minimized using least-squares approaches, leading to computationally efficient and fast converging algorithms. Several versions of this approach are developed and studied, some of which can be regarded as neural learning algorithms. A connection to the nonlinear PCA subspace rule is also shown. Experimental results are given, showing that the least-squares methods usually converge clearly faster than stochastic gradient algorithms in blind separation problems.     

Theoretical analysis of two ACO approaches for the traveling salesman problem

Bioinspired algorithms, such as evolutionary algorithms and ant colony optimization, are widely used for different combinatorial optimization problems. These algorithms rely heavily on the use of randomness and are hard to understand from a theoretical point of view. This paper contributes to the theoretical analysis of ant colony optimization and studies this type of algorithm on one of the most prominent combinatorial optimization problems, namely the traveling salesperson problem (TSP). We present a new construction graph and show that it has a stronger local property than one commonly used for constructing solutions of the TSP. The rigorous runtime analysis for two ant colony optimization algorithms, based on these two construction procedures, shows that they lead to good approximation in expected polynomial time on random instances. Furthermore, we point out in which situations our algorithms get trapped in local optima and show where the use of the right amount of heuristic information is provably beneficial.     

Resource-aware taxon selection for maximizing phylogenetic diversity

Phylogenetic diversity (PD) is a useful metric for selecting taxa in a range of biological applications, for example, bioconservation and genomics, where the selection is usually constrained by the limited availability of resources. We formalize taxon selection as a conceptually simple optimization problem, aiming to maximize PD subject to resource constraints. This allows us to take into account the different amounts of resources required by the different taxa. Although this is a computationally difficult problem, we present a dynamic programming algorithm that solves it in pseudo-polynomial time. Our algorithm can also solve many instances of the Noah's Ark Problem, a more realistic formulation of taxon selection for biodiversity conservation that allows for taxon-specific extinction risks. These instances extend the set of problems for which solutions are available beyond previously known greedy-tractable cases. Finally, we discuss the relevance of our results to real-life scenarios.     

An efficient approach to the travelling salesman problem using self-organizing maps

This paper presents an approach to the well-known Travelling Salesman Problem (TSP) using Self-Organizing Maps (SOM). The SOM algorithm has interesting topological information about its neurons configuration on cartesian space, which can be used to solve optimization problems. Aspects of initialization, parameters adaptation, and complexity analysis of the proposed SOM based algorithm are discussed. The results show an average deviation of 3.7% from the optimal tour length for a set of 12 TSP instances.     

Informational properties of neural nets performing algorithmic and logical tasks

It is argued that the genetic information necessary to encode an algorithmic neural processor tutoring an otherwise randomly connected biological neural net is represented by the entropy of the analogous minimal Turing machine. Such a near-minimal machine is constructed performing the whole range of bivalent propositional logic in variables. Neural nets computing the same task are presented; their informational entropy can be gauged with reference to the analogous Turing machine. It is also shown that nets with one hidden layer can be trained to perform algorithms solving propositional logic by error back-propagation. Received: 30 June 1995 / Accepted in revised form: 9 January 1996     

Heuristic combinatorial optimization by simulated Darwinian evolution: a polynomial time algorithm for the Traveling Salesman Problem

A genetic algorithm simulating Darwinian evolution is proposed to yield near-optimal solutions to the Traveling Salesman Problem. Noting that Darwinian evolution is itself an optimization process, we propose a heuristic algorithm that incorporates the tenets of natural selection. The time complexity of this algorithm is equivalent to the fastest sorting scheme! Computer simulations indicate rapid convergence is maintained even with increasing problem complexity. This methodology can be adapted to tackle a host of other combinatorial problems.     

Efficient parametric analysis of the chemical master equation through model order reduction

ABSTRACT: BACKGROUND: Stochastic biochemical reaction networks are commonly modelled by the chemical master equation, and can be simulated as first order linear differential equations through a finite state projection. Due to the very high state space dimension of these equations, numerical simulations are computationally expensive. This is a particular problem for analysis tasks requiring repeated simulations for different parameter values. Such tasks are computationally expensive to the point of infeasibility with the chemical master equation. RESULTS: In this article, we apply parametric model order reduction techniques in order to construct accurate low-dimensional parametric models of the chemical master equation. These surrogate models can be used in various parametric analysis task such as identifiability analysis, parameter estimation, or sensitivity analysis. As biological examples, we consider two models for gene regulation networks, a bistable switch and a network displaying stochastic oscillations. CONCLUSIONS: The results show that the parametric model reduction yields efficient models of stochastic biochemical reaction networks, and that these models can be useful for systems biology applications involving parametric analysis problems such as parameter exploration, optimization, estimation or sensitivity analysis.     

A neural net model for epilepsy

A neural net model based in our previous studies with randomly interconnected neural nets is presented here capable of exhibiting epileptic features. These features can be explained in terms of the structural and dynamical properties of the model. In addition, apart from the fact that this model can imitate epileptic phenomena, it might also help to explain some poorly understood clinical phenomena from which general disturbances can produce focal seizures in the brain.