Hierarchical Graphical Models for Multigroup Shape Analysis using Expectation Maximization with Sampling in Kendall's Shape Space

This paper proposes a novel framework for multi-group shape analysis relying on a hierarchical graphical statistical model on shapes within a population.The framework represents individual shapes as point setsmodulo translation, rotation, and scale, following the notion in Kendall shape space.While individual shapes are derived from their group shape model, each group shape model is derived from a single population shape model. The hierarchical model follows the natural organization of population data and the top level in the hierarchy provides a common frame of reference for multigroup shape analysis, e.g. classification and hypothesis testing. Unlike typical shape-modeling approaches, the proposed model is a generative model that defines a joint distribution of object-boundary data and the shape-model variables. Furthermore, it naturally enforces optimal correspondences during the process of model fitting and thereby subsumes the so-called correspondence problem. The proposed inference scheme employs an expectation maximization (EM) algorithm that treats the individual and group shape variables as hidden random variables and integrates them out before estimating the parameters (population mean and variance and the group variances). The underpinning of the EM algorithm is the sampling of pointsets, in Kendall shape space, from their posterior distribution, for which we exploit a highly-efficient scheme based on Hamiltonian Monte Carlo simulation. Experiments in this paper use the fitted hierarchical model to perform (1) hypothesis testing for comparison between pairs of groups using permutation testing and (2) classification for image retrieval. The paper validates the proposed framework on simulated data and demonstrates results on real data.Comment: 9 pages, 7 figures, International Conference on Machine Learning 201

On deep generative modelling methods for protein-protein interaction

Proteins form the basis for almost all biological processes, identifying the interactions that proteins have with themselves, the environment, and each other are critical to understanding their biological function in an organism, and thus the impact of drugs designed to affect them. Consequently a significant body of research and development focuses on methods to analyse and predict protein structure and interactions. Due to the breadth of possible interactions and the complexity of structures, \textit{in sillico} methods are used to propose models of both interaction and structure that can then be verified experimentally. However the computational complexity of protein interaction means that full physical simulation of these processes requires exceptional computational resources and is often infeasible. Recent advances in deep generative modelling have shown promise in correctly capturing complex conditional distributions. These models derive their basic principles from statistical mechanics and thermodynamic modelling. While the learned functions of these methods are not guaranteed to be physically accurate, they result in a similar sampling process to that suggested by the thermodynamic principles of protein folding and interaction. However, limited research has been applied to extending these models to work over the space of 3D rotation, limiting their applicability to protein models. In this thesis we develop an accelerated sampling strategy for faster sampling of potential docking locations, we then address the rotational diffusion limitation by extending diffusion models to the space of $SO(3)$ and finally present a framework for the use of this rotational diffusion model to rigid docking of proteins

Validação de heterogeneidade estrutural em dados de Crio-ME por comitês de agrupadores

Orientadores: Fernando José Von Zuben, Rodrigo Villares PortugalDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Elétrica e de ComputaçãoResumo: Análise de Partículas Isoladas é uma técnica que permite o estudo da estrutura tridimensional de proteínas e outros complexos macromoleculares de interesse biológico. Seus dados primários consistem em imagens de microscopia eletrônica de transmissão de múltiplas cópias da molécula em orientações aleatórias. Tais imagens são bastante ruidosas devido à baixa dose de elétrons utilizada. Reconstruções 3D podem ser obtidas combinando-se muitas imagens de partículas em orientações similares e estimando seus ângulos relativos. Entretanto, estados conformacionais heterogêneos frequentemente coexistem na amostra, porque os complexos moleculares podem ser flexíveis e também interagir com outras partículas. Heterogeneidade representa um desafio na reconstrução de modelos 3D confiáveis e degrada a resolução dos mesmos. Entre os algoritmos mais populares usados para classificação estrutural estão o agrupamento por k-médias, agrupamento hierárquico, mapas autoorganizáveis e estimadores de máxima verossimilhança. Tais abordagens estão geralmente entrelaçadas à reconstrução dos modelos 3D. No entanto, trabalhos recentes indicam ser possível inferir informações a respeito da estrutura das moléculas diretamente do conjunto de projeções 2D. Dentre estas descobertas, está a relação entre a variabilidade estrutural e manifolds em um espaço de atributos multidimensional. Esta dissertação investiga se um comitê de algoritmos de não-supervisionados é capaz de separar tais "manifolds conformacionais". Métodos de "consenso" tendem a fornecer classificação mais precisa e podem alcançar performance satisfatória em uma ampla gama de conjuntos de dados, se comparados a algoritmos individuais. Nós investigamos o comportamento de seis algoritmos de agrupamento, tanto individualmente quanto combinados em comitês, para a tarefa de classificação de heterogeneidade conformacional. A abordagem proposta foi testada em conjuntos sintéticos e reais contendo misturas de imagens de projeção da proteína Mm-cpn nos estados "aberto" e "fechado". Demonstra-se que comitês de agrupadores podem fornecer informações úteis na validação de particionamentos estruturais independetemente de algoritmos de reconstrução 3DAbstract: Single Particle Analysis is a technique that allows the study of the three-dimensional structure of proteins and other macromolecular assemblies of biological interest. Its primary data consists of transmission electron microscopy images from multiple copies of the molecule in random orientations. Such images are very noisy due to the low electron dose employed. Reconstruction of the macromolecule can be obtained by averaging many images of particles in similar orientations and estimating their relative angles. However, heterogeneous conformational states often co-exist in the sample, because the molecular complexes can be flexible and may also interact with other particles. Heterogeneity poses a challenge to the reconstruction of reliable 3D models and degrades their resolution. Among the most popular algorithms used for structural classification are k-means clustering, hierarchical clustering, self-organizing maps and maximum-likelihood estimators. Such approaches are usually interlaced with the reconstructions of the 3D models. Nevertheless, recent works indicate that it is possible to infer information about the structure of the molecules directly from the dataset of 2D projections. Among these findings is the relationship between structural variability and manifolds in a multidimensional feature space. This dissertation investigates whether an ensemble of unsupervised classification algorithms is able to separate these "conformational manifolds". Ensemble or "consensus" methods tend to provide more accurate classification and may achieve satisfactory performance across a wide range of datasets, when compared with individual algorithms. We investigate the behavior of six clustering algorithms both individually and combined in ensembles for the task of structural heterogeneity classification. The approach was tested on synthetic and real datasets containing a mixture of images from the Mm-cpn chaperonin in the "open" and "closed" states. It is shown that cluster ensembles can provide useful information in validating the structural partitionings independently of 3D reconstruction methodsMestradoEngenharia de ComputaçãoMestre em Engenharia Elétric

Learning Sampling-Based 6D Object Pose Estimation

The task of 6D object pose estimation, i.e. of estimating an object position (three degrees of freedom) and orientation (three degrees of freedom) from images is an essential building block of many modern applications, such as robotic grasping, autonomous driving, or augmented reality. Automatic pose estimation systems have to overcome a variety of visual ambiguities, including texture-less objects, clutter, and occlusion. Since many applications demand real time performance the efficient use of computational resources is an additional challenge. In this thesis, we will take a probabilistic stance on trying to overcome said issues. We build on a highly successful automatic pose estimation framework based on predicting pixel-wise correspondences between the camera coordinate system and the local coordinate system of the object. These dense correspondences are used to generate a pool of hypotheses, which in turn serve as a starting point in a final search procedure. We will present three systems that each use probabilistic modeling and sampling to improve upon different aspects of the framework. The goal of the first system, System I, is to enable pose tracking, i.e. estimating the pose of an object in a sequence of frames instead of a single image. By including information from previous frames tracking systems can resolve many visual ambiguities and reduce computation time. System I is a particle filter (PF) approach. The PF represents its belief about the pose in each frame by propagating a set of samples through time. Our system uses the process of hypothesis generation from the original framework as part of a proposal distribution that efficiently concentrates samples in the appropriate areas. In System II, we focus on the problem of evaluating the quality of pose hypotheses. This task plays an essential role in the final search procedure of the original framework. We use a convolutional neural network (CNN) to assess the quality of an hypothesis by comparing rendered and observed images. To train the CNN we view it as part of an energy-based probability distribution in pose space. This probabilistic perspective allows us to train the system under the maximum likelihood paradigm. We use a sampling approach to approximate the required gradients. The resulting system for pose estimation yields superior results in particular for highly occluded objects. In System III, we take the idea of machine learning a step further. Instead of learning to predict an hypothesis quality measure, to be used in a search procedure, we present a way of learning the search procedure itself. We train a reinforcement learning (RL) agent, termed PoseAgent, to steer the search process and make optimal use of a given computational budget. PoseAgent dynamically decides which hypothesis should be refined next, and which one should ultimately be output as final estimate. Since the search procedure includes discrete non-differentiable choices, training of the system via gradient descent is not easily possible. To solve the problem, we model behavior of PoseAgent as non-deterministic stochastic policy, which is ultimately governed by a CNN. This allows us to use a sampling-based stochastic policy gradient training procedure. We believe that some of the ideas developed in this thesis, such as the sampling-driven probabilistically motivated training of a CNN for the comparison of images or the search procedure implemented by PoseAgent have the potential to be applied in fields beyond pose estimation as well