54,774 research outputs found
BioEM: GPU-accelerated computing of Bayesian inference of electron microscopy images
In cryo-electron microscopy (EM), molecular structures are determined from
large numbers of projection images of individual particles. To harness the full
power of this single-molecule information, we use the Bayesian inference of EM
(BioEM) formalism. By ranking structural models using posterior probabilities
calculated for individual images, BioEM in principle addresses the challenge of
working with highly dynamic or heterogeneous systems not easily handled in
traditional EM reconstruction. However, the calculation of these posteriors for
large numbers of particles and models is computationally demanding. Here we
present highly parallelized, GPU-accelerated computer software that performs
this task efficiently. Our flexible formulation employs CUDA, OpenMP, and MPI
parallelization combined with both CPU and GPU computing. The resulting BioEM
software scales nearly ideally both on pure CPU and on CPU+GPU architectures,
thus enabling Bayesian analysis of tens of thousands of images in a reasonable
time. The general mathematical framework and robust algorithms are not limited
to cryo-electron microscopy but can be generalized for electron tomography and
other imaging experiments
Inference of Ancestral Recombination Graphs through Topological Data Analysis
The recent explosion of genomic data has underscored the need for
interpretable and comprehensive analyses that can capture complex phylogenetic
relationships within and across species. Recombination, reassortment and
horizontal gene transfer constitute examples of pervasive biological phenomena
that cannot be captured by tree-like representations. Starting from hundreds of
genomes, we are interested in the reconstruction of potential evolutionary
histories leading to the observed data. Ancestral recombination graphs
represent potential histories that explicitly accommodate recombination and
mutation events across orthologous genomes. However, they are computationally
costly to reconstruct, usually being infeasible for more than few tens of
genomes. Recently, Topological Data Analysis (TDA) methods have been proposed
as robust and scalable methods that can capture the genetic scale and frequency
of recombination. We build upon previous TDA developments for detecting and
quantifying recombination, and present a novel framework that can be applied to
hundreds of genomes and can be interpreted in terms of minimal histories of
mutation and recombination events, quantifying the scales and identifying the
genomic locations of recombinations. We implement this framework in a software
package, called TARGet, and apply it to several examples, including small
migration between different populations, human recombination, and horizontal
evolution in finches inhabiting the Gal\'apagos Islands.Comment: 33 pages, 12 figures. The accompanying software, instructions and
example files used in the manuscript can be obtained from
https://github.com/RabadanLab/TARGe
Paradigms for computational nucleic acid design
The design of DNA and RNA sequences is critical for many endeavors, from DNA nanotechnology, to PCR‐based applications, to DNA hybridization arrays. Results in the literature rely on a wide variety of design criteria adapted to the particular requirements of each application. Using an extensively studied thermodynamic model, we perform a detailed study of several criteria for designing sequences intended to adopt a target secondary structure. We conclude that superior design methods should explicitly implement both a positive design paradigm (optimize affinity for the target structure) and a negative design paradigm (optimize specificity for the target structure). The commonly used approaches of sequence symmetry minimization and minimum free‐energy satisfaction primarily implement negative design and can be strengthened by introducing a positive design component. Surprisingly, our findings hold for a wide range of secondary structures and are robust to modest perturbation of the thermodynamic parameters used for evaluating sequence quality, suggesting the feasibility and ongoing utility of a unified approach to nucleic acid design as parameter sets are refined further. Finally, we observe that designing for thermodynamic stability does not determine folding kinetics, emphasizing the opportunity for extending design criteria to target kinetic features of the energy landscape
"Going back to our roots": second generation biocomputing
Researchers in the field of biocomputing have, for many years, successfully
"harvested and exploited" the natural world for inspiration in developing
systems that are robust, adaptable and capable of generating novel and even
"creative" solutions to human-defined problems. However, in this position paper
we argue that the time has now come for a reassessment of how we exploit
biology to generate new computational systems. Previous solutions (the "first
generation" of biocomputing techniques), whilst reasonably effective, are crude
analogues of actual biological systems. We believe that a new, inherently
inter-disciplinary approach is needed for the development of the emerging
"second generation" of bio-inspired methods. This new modus operandi will
require much closer interaction between the engineering and life sciences
communities, as well as a bidirectional flow of concepts, applications and
expertise. We support our argument by examining, in this new light, three
existing areas of biocomputing (genetic programming, artificial immune systems
and evolvable hardware), as well as an emerging area (natural genetic
engineering) which may provide useful pointers as to the way forward.Comment: Submitted to the International Journal of Unconventional Computin
Emergent Properties of Tumor Microenvironment in a Real-life Model of Multicell Tumor Spheroids
Multicellular tumor spheroids are an important {\it in vitro} model of the
pre-vascular phase of solid tumors, for sizes well below the diagnostic limit:
therefore a biophysical model of spheroids has the ability to shed light on the
internal workings and organization of tumors at a critical phase of their
development. To this end, we have developed a computer program that integrates
the behavior of individual cells and their interactions with other cells and
the surrounding environment. It is based on a quantitative description of
metabolism, growth, proliferation and death of single tumor cells, and on
equations that model biochemical and mechanical cell-cell and cell-environment
interactions. The program reproduces existing experimental data on spheroids,
and yields unique views of their microenvironment. Simulations show complex
internal flows and motions of nutrients, metabolites and cells, that are
otherwise unobservable with current experimental techniques, and give novel
clues on tumor development and strong hints for future therapies.Comment: 20 pages, 10 figures. Accepted for publication in PLOS One. The
published version contains links to a supplementary text and three video
file
Symplectic quaternion scheme for biophysical molecular dynamics
Massively parallel biophysical molecular dynamics simulations, coupled with efficient methods, promise to open biologically significant time scales for study. In order to promote efficient fine-grained parallel algorithms with low communication overhead, the fast degrees of freedom in these complex systems can be divided into sets of rigid bodies. Here, a novel Hamiltonian form of a minimal, nonsingular representation of rigid body rotations, the unit quaternion, is derived, and a corresponding reversible, symplectic integrator is presented. The novel technique performs very well on both model and biophysical problems in accord with a formal theoretical analysis given within, which gives an explicit condition for an integrator to possess a conserved quantity, an explicit expression for the conserved quantity of a symplectic integrator, the latter following and in accord with Calvo and Sanz-Sarna, Numerical Hamiltonian Problems (1994), and extension of the explicit expression to general systems with a flat phase space
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