32,549 research outputs found
Representability of algebraic topology for biomolecules in machine learning based scoring and virtual screening
This work introduces a number of algebraic topology approaches, such as
multicomponent persistent homology, multi-level persistent homology and
electrostatic persistence for the representation, characterization, and
description of small molecules and biomolecular complexes. Multicomponent
persistent homology retains critical chemical and biological information during
the topological simplification of biomolecular geometric complexity.
Multi-level persistent homology enables a tailored topological description of
inter- and/or intra-molecular interactions of interest. Electrostatic
persistence incorporates partial charge information into topological
invariants. These topological methods are paired with Wasserstein distance to
characterize similarities between molecules and are further integrated with a
variety of machine learning algorithms, including k-nearest neighbors, ensemble
of trees, and deep convolutional neural networks, to manifest their descriptive
and predictive powers for chemical and biological problems. Extensive numerical
experiments involving more than 4,000 protein-ligand complexes from the PDBBind
database and near 100,000 ligands and decoys in the DUD database are performed
to test respectively the scoring power and the virtual screening power of the
proposed topological approaches. It is demonstrated that the present approaches
outperform the modern machine learning based methods in protein-ligand binding
affinity predictions and ligand-decoy discrimination
Quantitative toxicity prediction using topology based multi-task deep neural networks
The understanding of toxicity is of paramount importance to human health and
environmental protection. Quantitative toxicity analysis has become a new
standard in the field. This work introduces element specific persistent
homology (ESPH), an algebraic topology approach, for quantitative toxicity
prediction. ESPH retains crucial chemical information during the topological
abstraction of geometric complexity and provides a representation of small
molecules that cannot be obtained by any other method. To investigate the
representability and predictive power of ESPH for small molecules, ancillary
descriptors have also been developed based on physical models. Topological and
physical descriptors are paired with advanced machine learning algorithms, such
as deep neural network (DNN), random forest (RF) and gradient boosting decision
tree (GBDT), to facilitate their applications to quantitative toxicity
predictions. A topology based multi-task strategy is proposed to take the
advantage of the availability of large data sets while dealing with small data
sets. Four benchmark toxicity data sets that involve quantitative measurements
are used to validate the proposed approaches. Extensive numerical studies
indicate that the proposed topological learning methods are able to outperform
the state-of-the-art methods in the literature for quantitative toxicity
analysis. Our online server for computing element-specific topological
descriptors (ESTDs) is available at http://weilab.math.msu.edu/TopTox/Comment: arXiv admin note: substantial text overlap with arXiv:1703.1095
Synaptic Cleft Segmentation in Non-Isotropic Volume Electron Microscopy of the Complete Drosophila Brain
Neural circuit reconstruction at single synapse resolution is increasingly
recognized as crucially important to decipher the function of biological
nervous systems. Volume electron microscopy in serial transmission or scanning
mode has been demonstrated to provide the necessary resolution to segment or
trace all neurites and to annotate all synaptic connections.
Automatic annotation of synaptic connections has been done successfully in
near isotropic electron microscopy of vertebrate model organisms. Results on
non-isotropic data in insect models, however, are not yet on par with human
annotation.
We designed a new 3D-U-Net architecture to optimally represent isotropic
fields of view in non-isotropic data. We used regression on a signed distance
transform of manually annotated synaptic clefts of the CREMI challenge dataset
to train this model and observed significant improvement over the state of the
art.
We developed open source software for optimized parallel prediction on very
large volumetric datasets and applied our model to predict synaptic clefts in a
50 tera-voxels dataset of the complete Drosophila brain. Our model generalizes
well to areas far away from where training data was available
TopologyNet: Topology based deep convolutional neural networks for biomolecular property predictions
Although deep learning approaches have had tremendous success in image, video
and audio processing, computer vision, and speech recognition, their
applications to three-dimensional (3D) biomolecular structural data sets have
been hindered by the entangled geometric complexity and biological complexity.
We introduce topology, i.e., element specific persistent homology (ESPH), to
untangle geometric complexity and biological complexity. ESPH represents 3D
complex geometry by one-dimensional (1D) topological invariants and retains
crucial biological information via a multichannel image representation. It is
able to reveal hidden structure-function relationships in biomolecules. We
further integrate ESPH and convolutional neural networks to construct a
multichannel topological neural network (TopologyNet) for the predictions of
protein-ligand binding affinities and protein stability changes upon mutation.
To overcome the limitations to deep learning arising from small and noisy
training sets, we present a multitask topological convolutional neural network
(MT-TCNN). We demonstrate that the present TopologyNet architectures outperform
other state-of-the-art methods in the predictions of protein-ligand binding
affinities, globular protein mutation impacts, and membrane protein mutation
impacts.Comment: 20 pages, 8 figures, 5 table
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