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

Computational and Theoretical Issues of Multiparameter Persistent Homology for Data Analysis

The basic goal of topological data analysis is to apply topology-based descriptors to understand and describe the shape of data. In this context, homology is one of the most relevant topological descriptors, well-appreciated for its discrete nature, computability and dimension independence. A further development is provided by persistent homology, which allows to track homological features along a oneparameter increasing sequence of spaces. Multiparameter persistent homology, also called multipersistent homology, is an extension of the theory of persistent homology motivated by the need of analyzing data naturally described by several parameters, such as vector-valued functions. Multipersistent homology presents several issues in terms of feasibility of computations over real-sized data and theoretical challenges in the evaluation of possible descriptors. The focus of this thesis is in the interplay between persistent homology theory and discrete Morse Theory. Discrete Morse theory provides methods for reducing the computational cost of homology and persistent homology by considering the discrete Morse complex generated by the discrete Morse gradient in place of the original complex. The work of this thesis addresses the problem of computing multipersistent homology, to make such tool usable in real application domains. This requires both computational optimizations towards the applications to real-world data, and theoretical insights for finding and interpreting suitable descriptors. Our computational contribution consists in proposing a new Morse-inspired and fully discrete preprocessing algorithm. We show the feasibility of our preprocessing over real datasets, and evaluate the impact of the proposed algorithm as a preprocessing for computing multipersistent homology. A theoretical contribution of this thesis consists in proposing a new notion of optimality for such a preprocessing in the multiparameter context. We show that the proposed notion generalizes an already known optimality notion from the one-parameter case. Under this definition, we show that the algorithm we propose as a preprocessing is optimal in low dimensional domains. In the last part of the thesis, we consider preliminary applications of the proposed algorithm in the context of topology-based multivariate visualization by tracking critical features generated by a discrete gradient field compatible with the multiple scalar fields under study. We discuss (dis)similarities of such critical features with the state-of-the-art techniques in topology-based multivariate data visualization

Connections Between Adaptive Control and Optimization in Machine Learning

This paper demonstrates many immediate connections between adaptive control and optimization methods commonly employed in machine learning. Starting from common output error formulations, similarities in update law modifications are examined. Concepts in stability, performance, and learning, common to both fields are then discussed. Building on the similarities in update laws and common concepts, new intersections and opportunities for improved algorithm analysis are provided. In particular, a specific problem related to higher order learning is solved through insights obtained from these intersections.Comment: 18 page

The Challenge of Machine Learning in Space Weather Nowcasting and Forecasting

The numerous recent breakthroughs in machine learning (ML) make imperative to carefully ponder how the scientific community can benefit from a technology that, although not necessarily new, is today living its golden age. This Grand Challenge review paper is focused on the present and future role of machine learning in space weather. The purpose is twofold. On one hand, we will discuss previous works that use ML for space weather forecasting, focusing in particular on the few areas that have seen most activity: the forecasting of geomagnetic indices, of relativistic electrons at geosynchronous orbits, of solar flares occurrence, of coronal mass ejection propagation time, and of solar wind speed. On the other hand, this paper serves as a gentle introduction to the field of machine learning tailored to the space weather community and as a pointer to a number of open challenges that we believe the community should undertake in the next decade. The recurring themes throughout the review are the need to shift our forecasting paradigm to a probabilistic approach focused on the reliable assessment of uncertainties, and the combination of physics-based and machine learning approaches, known as gray-box.Comment: under revie

Discrete Differential Geometry

This is the collection of extended abstracts for the 26 lectures and the open problems session at the second Oberwolfach workshop on Discrete Differential Geometry