13,855 research outputs found
Spherical harmonics coeffcients for ligand-based virtual screening of cyclooxygenase inhibitors
Background: Molecular descriptors are essential for many applications in computational chemistry, such as ligand-based similarity searching. Spherical harmonics have previously been suggested as comprehensive descriptors of molecular structure and properties. We investigate a spherical harmonics descriptor for shape-based virtual screening. Methodology/Principal Findings: We introduce and validate a partially rotation-invariant three-dimensional molecular shape descriptor based on the norm of spherical harmonics expansion coefficients. Using this molecular representation, we parameterize molecular surfaces, i.e., isosurfaces of spatial molecular property distributions. We validate the shape descriptor in a comprehensive retrospective virtual screening experiment. In a prospective study, we virtually screen a large compound library for cyclooxygenase inhibitors, using a self-organizing map as a pre-filter and the shape descriptor for candidate prioritization. Conclusions/Significance: 12 compounds were tested in vitro for direct enzyme inhibition and in a whole blood assay. Active compounds containing a triazole scaffold were identified as direct cyclooxygenase-1 inhibitors. This outcome corroborates the usefulness of spherical harmonics for representation of molecular shape in virtual screening of large compound collections. The combination of pharmacophore and shape-based filtering of screening candidates proved to be a straightforward approach to finding novel bioactive chemotypes with minimal experimental effort
3D time series analysis of cell shape using Laplacian approaches
Background:
Fundamental cellular processes such as cell movement, division or food uptake critically depend on cells being able to change shape. Fast acquisition of three-dimensional image time series has now become possible, but we lack efficient tools for analysing shape deformations in order to understand the real three-dimensional nature of shape changes.
Results:
We present a framework for 3D+time cell shape analysis. The main contribution is three-fold: First, we develop a fast, automatic random walker method for cell segmentation. Second, a novel topology fixing method is proposed to fix segmented binary volumes without spherical topology. Third, we show that algorithms used for each individual step of the analysis pipeline (cell segmentation, topology fixing, spherical parameterization, and shape representation) are closely related to the Laplacian operator. The framework is applied to the shape analysis of neutrophil cells.
Conclusions:
The method we propose for cell segmentation is faster than the traditional random walker method or the level set method, and performs better on 3D time-series of neutrophil cells, which are comparatively noisy as stacks have to be acquired fast enough to account for cell motion. Our method for topology fixing outperforms the tools provided by SPHARM-MAT and SPHARM-PDM in terms of their successful fixing rates. The different tasks in the presented pipeline for 3D+time shape analysis of cells can be solved using Laplacian approaches, opening the possibility of eventually combining individual steps in order to speed up computations
Approximate Bayesian Image Interpretation using Generative Probabilistic Graphics Programs
The idea of computer vision as the Bayesian inverse problem to computer
graphics has a long history and an appealing elegance, but it has proved
difficult to directly implement. Instead, most vision tasks are approached via
complex bottom-up processing pipelines. Here we show that it is possible to
write short, simple probabilistic graphics programs that define flexible
generative models and to automatically invert them to interpret real-world
images. Generative probabilistic graphics programs consist of a stochastic
scene generator, a renderer based on graphics software, a stochastic likelihood
model linking the renderer's output and the data, and latent variables that
adjust the fidelity of the renderer and the tolerance of the likelihood model.
Representations and algorithms from computer graphics, originally designed to
produce high-quality images, are instead used as the deterministic backbone for
highly approximate and stochastic generative models. This formulation combines
probabilistic programming, computer graphics, and approximate Bayesian
computation, and depends only on general-purpose, automatic inference
techniques. We describe two applications: reading sequences of degraded and
adversarially obscured alphanumeric characters, and inferring 3D road models
from vehicle-mounted camera images. Each of the probabilistic graphics programs
we present relies on under 20 lines of probabilistic code, and supports
accurate, approximately Bayesian inferences about ambiguous real-world images.Comment: The first two authors contributed equally to this wor
Positive Definite Kernels in Machine Learning
This survey is an introduction to positive definite kernels and the set of
methods they have inspired in the machine learning literature, namely kernel
methods. We first discuss some properties of positive definite kernels as well
as reproducing kernel Hibert spaces, the natural extension of the set of
functions associated with a kernel defined
on a space . We discuss at length the construction of kernel
functions that take advantage of well-known statistical models. We provide an
overview of numerous data-analysis methods which take advantage of reproducing
kernel Hilbert spaces and discuss the idea of combining several kernels to
improve the performance on certain tasks. We also provide a short cookbook of
different kernels which are particularly useful for certain data-types such as
images, graphs or speech segments.Comment: draft. corrected a typo in figure
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