23,749 research outputs found
A view of Estimation of Distribution Algorithms through the lens of Expectation-Maximization
We show that a large class of Estimation of Distribution Algorithms,
including, but not limited to, Covariance Matrix Adaption, can be written as a
Monte Carlo Expectation-Maximization algorithm, and as exact EM in the limit of
infinite samples. Because EM sits on a rigorous statistical foundation and has
been thoroughly analyzed, this connection provides a new coherent framework
with which to reason about EDAs
Image tag completion by local learning
The problem of tag completion is to learn the missing tags of an image. In
this paper, we propose to learn a tag scoring vector for each image by local
linear learning. A local linear function is used in the neighborhood of each
image to predict the tag scoring vectors of its neighboring images. We
construct a unified objective function for the learning of both tag scoring
vectors and local linear function parame- ters. In the objective, we impose the
learned tag scoring vectors to be consistent with the known associations to the
tags of each image, and also minimize the prediction error of each local linear
function, while reducing the complexity of each local function. The objective
function is optimized by an alternate optimization strategy and gradient
descent methods in an iterative algorithm. We compare the proposed algorithm
against different state-of-the-art tag completion methods, and the results show
its advantages
First-principles molecular structure search with a genetic algorithm
The identification of low-energy conformers for a given molecule is a
fundamental problem in computational chemistry and cheminformatics. We assess
here a conformer search that employs a genetic algorithm for sampling the
low-energy segment of the conformation space of molecules. The algorithm is
designed to work with first-principles methods, facilitated by the
incorporation of local optimization and blacklisting conformers to prevent
repeated evaluations of very similar solutions. The aim of the search is not
only to find the global minimum, but to predict all conformers within an energy
window above the global minimum. The performance of the search strategy is: (i)
evaluated for a reference data set extracted from a database with amino acid
dipeptide conformers obtained by an extensive combined force field and
first-principles search and (ii) compared to the performance of a systematic
search and a random conformer generator for the example of a drug-like ligand
with 43 atoms, 8 rotatable bonds and 1 cis/trans bond
Navigating the protein fitness landscape with Gaussian processes
Knowing how protein sequence maps to function (the “fitness landscape”) is critical for understanding protein evolution as well as for engineering proteins with new and useful properties. We demonstrate that the protein fitness landscape can be inferred from experimental data, using Gaussian processes, a Bayesian learning technique. Gaussian process landscapes can model various protein sequence properties, including functional status, thermostability, enzyme activity, and ligand binding affinity. Trained on experimental data, these models achieve unrivaled quantitative accuracy. Furthermore, the explicit representation of model uncertainty allows for efficient searches through the vast space of possible sequences. We develop and test two protein sequence design algorithms motivated by Bayesian decision theory. The first one identifies small sets of sequences that are informative about the landscape; the second one identifies optimized sequences by iteratively improving the Gaussian process model in regions of the landscape that are predicted to be optimized. We demonstrate the ability of Gaussian processes to guide the search through protein sequence space by designing, constructing, and testing chimeric cytochrome P450s. These algorithms allowed us to engineer active P450 enzymes that are more thermostable than any previously made by chimeragenesis, rational design, or directed evolution
A topological approach for protein classification
Protein function and dynamics are closely related to its sequence and
structure. However prediction of protein function and dynamics from its
sequence and structure is still a fundamental challenge in molecular biology.
Protein classification, which is typically done through measuring the
similarity be- tween proteins based on protein sequence or physical
information, serves as a crucial step toward the understanding of protein
function and dynamics. Persistent homology is a new branch of algebraic
topology that has found its success in the topological data analysis in a
variety of disciplines, including molecular biology. The present work explores
the potential of using persistent homology as an indepen- dent tool for protein
classification. To this end, we propose a molecular topological fingerprint
based support vector machine (MTF-SVM) classifier. Specifically, we construct
machine learning feature vectors solely from protein topological fingerprints,
which are topological invariants generated during the filtration process. To
validate the present MTF-SVM approach, we consider four types of problems.
First, we study protein-drug binding by using the M2 channel protein of
influenza A virus. We achieve 96% accuracy in discriminating drug bound and
unbound M2 channels. Additionally, we examine the use of MTF-SVM for the
classification of hemoglobin molecules in their relaxed and taut forms and
obtain about 80% accuracy. The identification of all alpha, all beta, and
alpha-beta protein domains is carried out in our next study using 900 proteins.
We have found a 85% success in this identifica- tion. Finally, we apply the
present technique to 55 classification tasks of protein superfamilies over 1357
samples. An average accuracy of 82% is attained. The present study establishes
computational topology as an independent and effective alternative for protein
classification
ART: A machine learning Automated Recommendation Tool for synthetic biology
Biology has changed radically in the last two decades, transitioning from a descriptive science into a design science. Synthetic biology allows us to bioengineer cells to synthesize novel valuable molecules such as renewable biofuels or anticancer drugs. However, traditional synthetic biology approaches involve ad-hoc engineering practices, which lead to long development times. Here, we present the Automated Recommendation Tool (ART), a tool that leverages machine learning and probabilistic modeling techniques to guide synthetic biology in a systematic fashion, without the need for a full mechanistic understanding of the biological system. Using sampling-based optimization, ART provides a set of recommended strains to be built in the next engineering cycle, alongside probabilistic predictions of their production levels. We demonstrate the capabilities of ART on simulated data sets, as well as experimental data from real metabolic engineering projects producing renewable biofuels, hoppy flavored beer without hops, and fatty acids. Finally, we discuss the limitations of this approach, and the practical consequences of the underlying assumptions failing
Using numerical plant models and phenotypic correlation space to design achievable ideotypes
Numerical plant models can predict the outcome of plant traits modifications
resulting from genetic variations, on plant performance, by simulating
physiological processes and their interaction with the environment.
Optimization methods complement those models to design ideotypes, i.e. ideal
values of a set of plant traits resulting in optimal adaptation for given
combinations of environment and management, mainly through the maximization of
a performance criteria (e.g. yield, light interception). As use of simulation
models gains momentum in plant breeding, numerical experiments must be
carefully engineered to provide accurate and attainable results, rooting them
in biological reality. Here, we propose a multi-objective optimization
formulation that includes a metric of performance, returned by the numerical
model, and a metric of feasibility, accounting for correlations between traits
based on field observations. We applied this approach to two contrasting
models: a process-based crop model of sunflower and a functional-structural
plant model of apple trees. In both cases, the method successfully
characterized key plant traits and identified a continuum of optimal solutions,
ranging from the most feasible to the most efficient. The present study thus
provides successful proof of concept for this enhanced modeling approach, which
identified paths for desirable trait modification, including direction and
intensity.Comment: 25 pages, 5 figures, 2017, Plant, Cell and Environmen
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