BOOL-AN: A method for comparative sequence analysis and phylogenetic reconstruction

A novel discrete mathematical approach is proposed as an additional tool for molecular systematics which does not require prior statistical assumptions concerning the evolutionary process. The method is based on algorithms generating mathematical representations directly from DNA/RNA or protein sequences, followed by the output of numerical (scalar or vector) and visual characteristics (graphs). The binary encoded sequence information is transformed into a compact analytical form, called the Iterative Canonical Form (or ICF) of Boolean functions, which can then be used as a generalized molecular descriptor. The method provides raw vector data for calculating different distance matrices, which in turn can be analyzed by neighbor-joining or UPGMA to derive a phylogenetic tree, or by principal coordinates analysis to get an ordination scattergram. The new method and the associated software for inferring phylogenetic trees are called the Boolean analysis or BOOL-AN

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

Metric Learning for Generalizing Spatial Relations to New Objects

Human-centered environments are rich with a wide variety of spatial relations between everyday objects. For autonomous robots to operate effectively in such environments, they should be able to reason about these relations and generalize them to objects with different shapes and sizes. For example, having learned to place a toy inside a basket, a robot should be able to generalize this concept using a spoon and a cup. This requires a robot to have the flexibility to learn arbitrary relations in a lifelong manner, making it challenging for an expert to pre-program it with sufficient knowledge to do so beforehand. In this paper, we address the problem of learning spatial relations by introducing a novel method from the perspective of distance metric learning. Our approach enables a robot to reason about the similarity between pairwise spatial relations, thereby enabling it to use its previous knowledge when presented with a new relation to imitate. We show how this makes it possible to learn arbitrary spatial relations from non-expert users using a small number of examples and in an interactive manner. Our extensive evaluation with real-world data demonstrates the effectiveness of our method in reasoning about a continuous spectrum of spatial relations and generalizing them to new objects.Comment: Accepted at the 2017 IEEE/RSJ International Conference on Intelligent Robots and Systems. The new Freiburg Spatial Relations Dataset and a demo video of our approach running on the PR-2 robot are available at our project website: http://spatialrelations.cs.uni-freiburg.d