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

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

A topological approach for protein classification

Protein function and dynamics are closely related to its sequence and structure. However prediction of protein function and dynamics from its sequence and structure is still a fundamental challenge in molecular biology. Protein classification, which is typically done through measuring the similarity be- tween proteins based on protein sequence or physical information, serves as a crucial step toward the understanding of protein function and dynamics. Persistent homology is a new branch of algebraic topology that has found its success in the topological data analysis in a variety of disciplines, including molecular biology. The present work explores the potential of using persistent homology as an indepen- dent tool for protein classification. To this end, we propose a molecular topological fingerprint based support vector machine (MTF-SVM) classifier. Specifically, we construct machine learning feature vectors solely from protein topological fingerprints, which are topological invariants generated during the filtration process. To validate the present MTF-SVM approach, we consider four types of problems. First, we study protein-drug binding by using the M2 channel protein of influenza A virus. We achieve 96% accuracy in discriminating drug bound and unbound M2 channels. Additionally, we examine the use of MTF-SVM for the classification of hemoglobin molecules in their relaxed and taut forms and obtain about 80% accuracy. The identification of all alpha, all beta, and alpha-beta protein domains is carried out in our next study using 900 proteins. We have found a 85% success in this identifica- tion. Finally, we apply the present technique to 55 classification tasks of protein superfamilies over 1357 samples. An average accuracy of 82% is attained. The present study establishes computational topology as an independent and effective alternative for protein classification

A biophysical approach to large-scale protein-DNA binding data

About this book * Cutting-edge genome analysis methods from leading bioinformaticians An accurate description of current scientific developments in the field of bioinformatics and computational implementation is presented by research of the BioSapiens Network of Excellence. Bioinformatics is essential for annotating the structure and function of genes, proteins and the analysis of complete genomes and to molecular biology and biochemistry. Included is an overview of bioinformatics, the full spectrum of genome annotation approaches including; genome analysis and gene prediction, gene regulation analysis and expression, genome variation and QTL analysis, large scale protein annotation of function and structure, annotation and prediction of protein interactions, and the organization and annotation of molecular networks and biochemical pathways. Also covered is a technical framework to organize and represent genome data using the DAS technology and work in the annotation of two large genomic sets: HIV/HCV viral genomes and splicing alternatives potentially encoded in 1% of the human genome

edge2vec: Representation learning using edge semantics for biomedical knowledge discovery

Representation learning provides new and powerful graph analytical approaches and tools for the highly valued data science challenge of mining knowledge graphs. Since previous graph analytical methods have mostly focused on homogeneous graphs, an important current challenge is extending this methodology for richly heterogeneous graphs and knowledge domains. The biomedical sciences are such a domain, reflecting the complexity of biology, with entities such as genes, proteins, drugs, diseases, and phenotypes, and relationships such as gene co-expression, biochemical regulation, and biomolecular inhibition or activation. Therefore, the semantics of edges and nodes are critical for representation learning and knowledge discovery in real world biomedical problems. In this paper, we propose the edge2vec model, which represents graphs considering edge semantics. An edge-type transition matrix is trained by an Expectation-Maximization approach, and a stochastic gradient descent model is employed to learn node embedding on a heterogeneous graph via the trained transition matrix. edge2vec is validated on three biomedical domain tasks: biomedical entity classification, compound-gene bioactivity prediction, and biomedical information retrieval. Results show that by considering edge-types into node embedding learning in heterogeneous graphs, \textbf{edge2vec}\ significantly outperforms state-of-the-art models on all three tasks. We propose this method for its added value relative to existing graph analytical methodology, and in the real world context of biomedical knowledge discovery applicability.Comment: 10 page

Creating, Modeling, and Visualizing Metabolic Networks

Metabolic networks combine metabolism and regulation. These complex networks are difficult to understand and create due to the diverse types of information that need to be represented. This chapter describes a suite of interlinked tools for developing, displaying, and modeling metabolic networks. The metabolic network interactions database, MetNetDB, contains information on regulatory and metabolic interactions derived from a combination of web databases and input from biologists in their area of expertise. PathBinderA mines the biological “literaturome” by searching for new interactions or supporting evidence for existing interactions in metabolic networks. Sentences from abstracts are ranked in terms of the likelihood that an interaction is described and combined with evidence provided by other sentences. FCModeler, a publicly available software package, enables the biologist to visualize and model metabolic and regulatory network maps. FCModeler aids in the development and evaluation of hypotheses, and provides a modeling framework for assessing the large amounts of data captured by high-throughput gene expression experiments