31,718 research outputs found
How round is a protein? Exploring protein structures for globularity using conformal mapping.
We present a new algorithm that automatically computes a measure of the geometric difference between the surface of a protein and a round sphere. The algorithm takes as input two triangulated genus zero surfaces representing the protein and the round sphere, respectively, and constructs a discrete conformal map f between these surfaces. The conformal map is chosen to minimize a symmetric elastic energy E S (f) that measures the distance of f from an isometry. We illustrate our approach on a set of basic sample problems and then on a dataset of diverse protein structures. We show first that E S (f) is able to quantify the roundness of the Platonic solids and that for these surfaces it replicates well traditional measures of roundness such as the sphericity. We then demonstrate that the symmetric elastic energy E S (f) captures both global and local differences between two surfaces, showing that our method identifies the presence of protruding regions in protein structures and quantifies how these regions make the shape of a protein deviate from globularity. Based on these results, we show that E S (f) serves as a probe of the limits of the application of conformal mapping to parametrize protein shapes. We identify limitations of the method and discuss its extension to achieving automatic registration of protein structures based on their surface geometry
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Ensemble learning of model hyperparameters and spatiotemporal data for calibration of low-cost PM2.5 sensors.
he PM2.5 air quality index (AQI) measurements from government-built supersites are accurate but cannot provide a dense coverage of monitoring areas. Low-cost PM2.5 sensors can be used to deploy a fine-grained internet-of-things (IoT) as a complement to government facilities. Calibration of low-cost sensors by reference to high-accuracy supersites is thus essential. Moreover, the imputation for missing-value in training data may affect the calibration result, the best performance of calibration model requires hyperparameter optimization, and the affecting factors of PM2.5 concentrations such as climate, geographical landscapes and anthropogenic activities are uncertain in spatial and temporal dimensions. In this paper, an ensemble learning for imputation method selection, calibration model hyperparameterization, and spatiotemporal training data composition is proposed. Three government supersites are chosen in central Taiwan for the deployment of low-cost sensors and hourly PM2.5 measurements are collected for 60 days for conducting experiments. Three optimizers, Sobol sequence, Nelder and Meads, and particle swarm optimization (PSO), are compared for evaluating their performances with various versions of ensembles. The best calibration results are obtained by using PSO, and the improvement ratios with respect to R2, RMSE, and NME, are 4.92%, 52.96%, and 56.85%, respectively
In Silico Synchronization of Cellular Populations Through Expression Data Deconvolution
Cellular populations are typically heterogenous collections of cells at
different points in their respective cell cycles, each with a cell cycle time
that varies from individual to individual. As a result, true single-cell
behavior, particularly that which is cell-cycle--dependent, is often obscured
in population-level (averaged) measurements. We have developed a simple
deconvolution method that can be used to remove the effects of asynchronous
variability from population-level time-series data. In this paper, we summarize
some recent progress in the development and application of our approach, and
provide technical updates that result in increased biological fidelity. We also
explore several preliminary validation results and discuss several ongoing
applications that highlight the method's usefulness for estimating parameters
in differential equation models of single-cell gene regulation.Comment: accepted for the 48th ACM/IEEE Design Automation Conferenc
An Introduction to Programming for Bioscientists: A Python-based Primer
Computing has revolutionized the biological sciences over the past several
decades, such that virtually all contemporary research in the biosciences
utilizes computer programs. The computational advances have come on many
fronts, spurred by fundamental developments in hardware, software, and
algorithms. These advances have influenced, and even engendered, a phenomenal
array of bioscience fields, including molecular evolution and bioinformatics;
genome-, proteome-, transcriptome- and metabolome-wide experimental studies;
structural genomics; and atomistic simulations of cellular-scale molecular
assemblies as large as ribosomes and intact viruses. In short, much of
post-genomic biology is increasingly becoming a form of computational biology.
The ability to design and write computer programs is among the most
indispensable skills that a modern researcher can cultivate. Python has become
a popular programming language in the biosciences, largely because (i) its
straightforward semantics and clean syntax make it a readily accessible first
language; (ii) it is expressive and well-suited to object-oriented programming,
as well as other modern paradigms; and (iii) the many available libraries and
third-party toolkits extend the functionality of the core language into
virtually every biological domain (sequence and structure analyses,
phylogenomics, workflow management systems, etc.). This primer offers a basic
introduction to coding, via Python, and it includes concrete examples and
exercises to illustrate the language's usage and capabilities; the main text
culminates with a final project in structural bioinformatics. A suite of
Supplemental Chapters is also provided. Starting with basic concepts, such as
that of a 'variable', the Chapters methodically advance the reader to the point
of writing a graphical user interface to compute the Hamming distance between
two DNA sequences.Comment: 65 pages total, including 45 pages text, 3 figures, 4 tables,
numerous exercises, and 19 pages of Supporting Information; currently in
press at PLOS Computational Biolog
Time-delayed models of gene regulatory networks
We discuss different mathematical models of gene regulatory networks as relevant to the onset and development of cancer. After discussion of alternativemodelling approaches, we use a paradigmatic two-gene network to focus on the role played by time delays in the dynamics of gene regulatory networks. We contrast the dynamics of the reduced model arising in the limit of fast mRNA dynamics with that of the full model. The review concludes with the discussion of some open problems
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