A Transformative Topological Representation for Link Modeling, Prediction and Cross-Domain Network Analysis.

Many complex social, biological, or physical systems are characterized as networks, and recovering the missing links of a network could shed important lights on its structure and dynamics. A good topological representation is crucial to accurate link modeling and prediction, yet how to account for the kaleidoscopic changes in link formation patterns remains a challenge, especially for analysis in cross-domain studies. We propose a new link representation scheme by projecting the local environment of a link into a "dipole plane", where neighboring nodes of the link are positioned via their relative proximity to the two anchors of the link, like a dipole. By doing this, complex and discrete topology arising from link formation is turned to differentiable point-cloud distribution, opening up new possibilities for topological feature-engineering with desired expressiveness, interpretability and generalization. Our approach has comparable or even superior results against state-of-the-art GNNs, meanwhile with a model up to hundreds of times smaller and running much faster. Furthermore, it provides a universal platform to systematically profile, study, and compare link-patterns from miscellaneous real-world networks. This allows building a global link-pattern atlas, based on which we have uncovered interesting common patterns of link formation, i.e., the bridge-style, the radiation-style, and the community-style across a wide collection of networks with highly different nature.

Multi-modal chemical information reconstruction from images and texts for exploring the near-drug space.

Identification of new chemical compounds with desired structural diversity and biological properties plays an essential role in drug discovery, yet the construction of such a potential space with elements of 'near-drug' properties is still a challenging task. In this work, we proposed a multimodal chemical information reconstruction system to automatically process, extract and align heterogeneous information from the text descriptions and structural images of chemical patents. Our key innovation lies in a heterogeneous data generator that produces cross-modality training data in the form of text descriptions and Markush structure images, from which a two-branch model with image- and text-processing units can then learn to both recognize heterogeneous chemical entities and simultaneously capture their correspondence. In particular, we have collected chemical structures from ChEMBL database and chemical patents from the European Patent Office and the US Patent and Trademark Office using keywords 'A61P, compound, structure' in the years from 2010 to 2020, and generated heterogeneous chemical information datasets with 210K structural images and 7818 annotated text snippets. Based on the reconstructed results and substituent replacement rules, structural libraries of a huge number of near-drug compounds can be generated automatically. In quantitative evaluations, our model can correctly reconstruct 97% of the molecular images into structured format and achieve an F1-score around 97-98% in the recognition of chemical entities, which demonstrated the effectiveness of our model in automatic information extraction from chemical patents, and hopefully transforming them to a user-friendly, structured molecular database enriching the near-drug space to realize the intelligent retrieval technology of chemical knowledge.

VRPharmer: bringing virtual reality into pharmacophore-based virtual screening with interactive exploration and realistic visualization.

SUMMARY: Current pharmacophore-based virtual screening (VS) software has limited interactive capabilities and less intuitive screening processes. In this study, a novel tool named VRPharmer is proposed to perform the entire VS workflow in VR environments. VRPharmer enables users to interactively perceive computation processes and immersively observe molecular structures. Besides a typical screening mode (OPT mode), VRPharmer provides a unique interactive screening mode (SCORE mode) for freely exploring the optimal binding poses. Pharmacophore models are editable to study the impact of each feature and further refine the screening results. Moreover, molecular rendering algorithms are improved for precise representations. AVAILABILITY AND IMPLEMENTATION: VRPharmer is open-source software under the MIT license. The released version is available at https://github.com/VRPharmer/VRPharmer. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

F2-Bubbles: Faithful Bubble Set Construction and Flexible Editing.

In this paper, we propose F2-Bubbles, a set overlay visualization technique that addresses overlapping artifacts and supports interactive editing with intelligent suggestions. The core of our method is a new, efficient set overlay construction algorithm that approximates the optimal set overlay by considering set elements and their non-set neighbors. Thanks to the efficiency of the algorithm, interactive editing is achieved, and with intelligent suggestions, users can easily and flexibly edit visualizations through direct manipulations with local adaptations. A quantitative comparison with state-of-the-art set visualization techniques and case studies demonstrate the effectiveness of our method and suggests that F2-Bubbles is a helpful technique for set visualization.

ePharmer: An integrated and graphical software for pharmacophore-based virtual screening.

Pharmacophore-based virtual screening (VS) has emerged as an efficient computer-aided drug design technique when appraising multiple ligands with similar structures or targets with unknown crystal structures. Current pharmacophore modeling and analysis software suffers from inadequate integration of mainstream methods and insufficient user-friendly program interface. In this study, we propose a stand-alone, integrated, graphical software for pharmacophore-based VS, termed ePharmer. Both ligand-based and structure-based pharmacophore generation methods were integrated into a compact architecture. Fine-grained modules were carefully organized into the computing, integration, and visualization layers. Graphical design covered the global user interface and specific user operations including editing, evaluation, and task management. Metabolites prediction analysis with the chosen VS result is provided for preselection of wet experiments. Moreover, the underlying computing units largely adopted the preliminary work of our research team. The presented software is currently in client use and will be released for both professional and nonexpert users. Experimental results verified the favorable computing capability, user convenience, and case performance of the proposed software.

eSHAFTS: Integrated and graphical drug design software based on 3D molecular similarity.

With the development of computer technology, computer-aided drug design (CADD) has become an important means for drug research and development, and its representative method is virtual screening. Various virtual screening platforms have emerged in an endless stream and play great roles in the field of drug discovery. With the increasing number of compound molecules, virtual screening platforms face two challenges: low fluency and low visibility of software operations. In this article, we present an integrated and graphical drug design software eSHAFTS based on three-dimensional (3D) molecular similarity to overcome these shortcomings. Compared with other software, eSHAFTS has four main advantages, which are integrated molecular editing and drawing, interactive loading and analysis of proteins, multithread and multimode 3D molecular similarity calculation, and multidimensional information visualization. Experiments have verified its convenience, usability, and reliability. By using eSHAFTS, various tasks can be submitted and visualized in one desktop software without locally installing any dependent plug-ins or software. The software installation package can be downloaded for free at http://lilab.ecust.edu.cn/home/resource.html. © 2019 Wiley Periodicals, Inc.

An Improved Receptor-Based Pharmacophore Generation Algorithm Guided by Atomic Chemical Characteristics and Hybridization Types.

Pharmacophore-based virtual screening is an important and leading compound discovery method. However, current pharmacophore generation algorithms suffer from difficulties, such as ligand-dependent computation and massive extractive chemical features. On the basis of the features extracted by the five probes in Pocket v.3, this paper presents an improved receptor-based pharmacophore generation algorithm guided by atomic chemical characteristics and hybridization types. The algorithm works under the constraint of receptor atom hybridization types and space distance. Four chemical characteristics (H-A, H-D, and positive and negative charges) were extracted using the hybridization type of receptor atoms, and the feature point sets were merged with 3 Å space constraints. Furthermore, on the basis of the original extraction of hydrophobic characteristics, extraction of aromatic ring chemical characteristics was achieved by counting the number of aromatics, searching for residual base aromatic ring, and determining the direction of aromatic rings. Accordingly, extraction of six kinds of chemical characteristics of the pharmacophore was achieved. In view of the pharmacophore characteristics, our algorithm was compared with the existing LigandScout algorithm. The results demonstrate that the pharmacophore possessing six chemical characteristics can be characterized using our algorithm, which features fewer pharmacophore characteristics and is ligand independent. The computation of many instances from the directory of useful decoy dataset show that the active molecules and decoy molecules can be effectively differentiated through the presented method in this paper.

Keeping speed and distance for aligned motion.

The cohesive collective motion (flocking, swarming) of autonomous agents is ubiquitously observed and exploited in both natural and man-made settings, thus, minimal models for its description are essential. In a model with continuous space and time we find that if two particles arrive symmetrically in a plane at a large angle, then (i) radial repulsion and (ii) linear self-propelling toward a fixed preferred speed are sufficient for them to depart at a smaller angle. For this local gain of momentum explicit velocity alignment is not necessary, nor are adhesion or attraction, inelasticity or anisotropy of the particles, or nonlinear drag. With many particles obeying these microscopic rules of motion we find that their spatial confinement to a square with periodic boundaries (which is an indirect form of attraction) leads to stable macroscopic ordering. As a function of the strength of added noise we see--at finite system sizes--a critical slowing down close to the order-disorder boundary and a discontinuous transition. After varying the density of particles at constant system size and varying the size of the system with constant particle density we predict that in the infinite system size (or density) limit the hysteresis loop disappears and the transition becomes continuous. We note that animals, humans, drones, etc., tend to move asynchronously and are often more responsive to motion than positions. Thus, for them velocity-based continuous models can provide higher precision than coordinate-based models. An additional characteristic and realistic feature of the model is that convergence to the ordered state is fastest at a finite density, which is in contrast to models applying (discontinuous) explicit velocity alignments and discretized time. To summarize, we find that the investigated model can provide a minimal description of flocking.