Combining multiple classifications of chemical structures using consensus clustering

Consensus clustering involves combining multiple clusterings of the same set of objects to achieve a single clustering that will, hopefully, provide a better picture of the groupings that are present in a dataset. This Letter reports the use of consensus clustering methods on sets of chemical compounds represented by 2D fingerprints. Experiments with DUD, IDAlert, MDDR and MUV data suggests that consensus methods are unlikely to result in significant improvements in clustering effectiveness as compared to the use of a single clustering method. (C) 2012 Elsevier Ltd. All rights reserved

Merging KK-means with hierarchical clustering for identifying general-shaped groups

Clustering partitions a dataset such that observations placed together in a group are similar but different from those in other groups. Hierarchical and $K$-means clustering are two approaches but have different strengths and weaknesses. For instance, hierarchical clustering identifies groups in a tree-like structure but suffers from computational complexity in large datasets while $K$-means clustering is efficient but designed to identify homogeneous spherically-shaped clusters. We present a hybrid non-parametric clustering approach that amalgamates the two methods to identify general-shaped clusters and that can be applied to larger datasets. Specifically, we first partition the dataset into spherical groups using $K$-means. We next merge these groups using hierarchical methods with a data-driven distance measure as a stopping criterion. Our proposal has the potential to reveal groups with general shapes and structure in a dataset. We demonstrate good performance on several simulated and real datasets.Comment: 16 pages, 1 table, 9 figures; accepted for publication in Sta

Bayesian nonparametric clusterings in relational and high-dimensional settings with applications in bioinformatics.

Recent advances in high throughput methodologies offer researchers the ability to understand complex systems via high dimensional and multi-relational data. One example is the realm of molecular biology where disparate data (such as gene sequence, gene expression, and interaction information) are available for various snapshots of biological systems. This type of high dimensional and multirelational data allows for unprecedented detailed analysis, but also presents challenges in accounting for all the variability. High dimensional data often has a multitude of underlying relationships, each represented by a separate clustering structure, where the number of structures is typically unknown a priori. To address the challenges faced by traditional clustering methods on high dimensional and multirelational data, we developed three feature selection and cross-clustering methods: 1) infinite relational model with feature selection (FIRM) which incorporates the rich information of multirelational data; 2) Bayesian Hierarchical Cross-Clustering (BHCC), a deterministic approximation to Cross Dirichlet Process mixture (CDPM) and to cross-clustering; and 3) randomized approximation (RBHCC), based on a truncated hierarchy. An extension of BHCC, Bayesian Congruence Measuring (BCM), is proposed to measure incongruence between genes and to identify sets of congruent loci with identical evolutionary histories. We adapt our BHCC algorithm to the inference of BCM, where the intended structure of each view (congruent loci) represents consistent evolutionary processes. We consider an application of FIRM on categorizing mRNA and microRNA. The model uses latent structures to encode the expression pattern and the gene ontology annotations. We also apply FIRM to recover the categories of ligands and proteins, and to predict unknown drug-target interactions, where latent categorization structure encodes drug-target interaction, chemical compound similarity, and amino acid sequence similarity. BHCC and RBHCC are shown to have improved predictive performance (both in terms of cluster membership and missing value prediction) compared to traditional clustering methods. Our results suggest that these novel approaches to integrating multi-relational information have a promising future in the biological sciences where incorporating data related to varying features is often regarded as a daunting task

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

Clustering for 2D chemical structures

The clustering of chemical structures is important and widely used in several areas of chemoinformatics. A little-discussed aspect of clustering is standardization, it ensures all descriptors in a chemical representation make a comparable contribution to the measurement of similarity. The initial study compares the effectiveness of seven different standardization procedures that have been suggested previously, the results were also compared with unstandardized datasets. It was found that no one standardization method offered consistently the best performance. Comparative studies of clustering effectiveness are helpful in providing suitability and guidelines of different methods. In order to examine the suitability of different clustering methods for the application in chemoinformatics, especially those had not previously been applied to chemoinformatics, the second piece of study carries out an effectiveness comparison of nine clustering methods. However, the result revealed that it is unlikely that a single clustering method can provide consistently the best partition under all circumstances. Consensus clustering is a technique to combine multiple input partitions of the same set of objects to achieve a single clustering that is expected to provide a more robust and more generally effective representation of the partitions that are submitted. The third piece of study reports the use of seven different consensus clustering methods which had not previously been used on sets of chemical compounds represented by 2D fingerprints. Their effectiveness was compared with some traditional clustering methods discussed in the second study. It was observed that no consistently best consensus clustering method was found

Graph set data mining

Graphs are among the most versatile abstract data types in computer science. With the variety comes great adoption in various application fields, such as chemistry, biology, social analysis, logistics, and computer science itself. With the growing capacities of digital storage, the collection of large amounts of data has become the norm in many application fields. Data mining, i.e., the automated extraction of non-trivial patterns from data, is a key step to extract knowledge from these datasets and generate value. This thesis is dedicated to concurrent scalable data mining algorithms beyond traditional notions of efficiency for large-scale datasets of small labeled graphs; more precisely, structural clustering and representative subgraph pattern mining. It is motivated by, but not limited to, the need to analyze molecular libraries of ever-increasing size in the drug discovery process. Structural clustering makes use of graph theoretical concepts, such as (common) subgraph isomorphisms and frequent subgraphs, to model cluster commonalities directly in the application domain. It is considered computationally demanding for non-restricted graph classes and with very few exceptions prior algorithms are only suitable for very small datasets. This thesis discusses the first truly scalable structural clustering algorithm StruClus with linear worst-case complexity. At the same time, StruClus embraces the inherent values of structural clustering algorithms, i.e., interpretable, consistent, and high-quality results. A novel two-fold sampling strategy with stochastic error bounds for frequent subgraph mining is presented. It enables fast extraction of cluster commonalities in the form of common subgraph representative sets. StruClus is the first structural clustering algorithm with a directed selection of structural cluster-representative patterns regarding homogeneity and separation aspects in the high-dimensional subgraph pattern space. Furthermore, a novel concept of cluster homogeneity balancing using dynamically-sized representatives is discussed. The second part of this thesis discusses the representative subgraph pattern mining problem in more general terms. A novel objective function maximizes the number of represented graphs for a cardinality-constrained representative set. It is shown that the problem is a special case of the maximum coverage problem and is NP-hard. Based on the greedy approximation of Nemhauser, Wolsey, and Fisher for submodular set function maximization a novel sampling approach is presented. It mines candidate sets that contain an optimal greedy solution with a probabilistic maximum error. This leads to a constant-time algorithm to generate the candidate sets given a fixed-size sample of the dataset. In combination with a cheap single-pass streaming evaluation of the candidate sets, this enables scalability to datasets with billions of molecules on a single machine. Ultimately, the sampling approach leads to the first distributed subgraph pattern mining algorithm that distributes the pattern space and the dataset graphs at the same time

Weighting Policies for Robust Unsupervised Ensemble Learning

The unsupervised ensemble learning, or consensus clustering, consists of finding the optimal com- bination strategy of individual partitions that is robust in comparison to the selection of an algorithmic clustering pool. Despite its strong properties, this approach assigns the same weight to the contribution of each clustering to the final solution. We propose a weighting policy for this problem that is based on internal clustering quality measures and compare against other modern approaches. Results on publicly available datasets show that weights can significantly improve the accuracy performance while retaining the robust properties. Since the issue of determining an appropriate number of clusters, which is a primary input for many clustering methods is one of the significant challenges, we have used the same methodology to predict correct or the most suitable number of clusters as well. Among various methods, using internal validity indexes in conjunction with a suitable algorithm is one of the most popular way to determine the appropriate number of cluster. Thus, we use weighted consensus clustering along with four different indexes which are Silhouette (SH), Calinski-Harabasz (CH), Davies-Bouldin (DB), and Consensus (CI) indexes. Our experiment indicates that weighted consensus clustering together with chosen indexes is a useful method to determine right or the most appropriate number of clusters in comparison to individual clustering methods (e.g., k-means) and consensus clustering. Lastly, to decrease the variance of proposed weighted consensus clustering, we borrow the idea of Markowitz portfolio theory and implement its core idea to clustering domain. We aim to optimize the combination of individual clustering methods to minimize the variance of clustering accuracy. This is a new weighting policy to produce partition with a lower variance which might be crucial for a decision maker. Our study shows that using the idea of Markowitz portfolio theory will create a partition with a less variation in comparison to traditional consensus clustering and proposed weighted consensus clustering

Ensemble clustering via heuristic optimisation

This thesis was submitted for the degree of Doctor of Philosophy and was awarded by Brunel UniversityTraditional clustering algorithms have different criteria and biases, and there is no single algorithm that can be the best solution for a wide range of data sets. This problem often presents a significant obstacle to analysts in revealing meaningful information buried among the huge amount of data. Ensemble Clustering has been proposed as a way to avoid the biases and improve the accuracy of clustering. The difficulty in developing Ensemble Clustering methods is to combine external information (provided by input clusterings) with internal information (i.e. characteristics of given data) effectively to improve the accuracy of clustering. The work presented in this thesis focuses on enhancing the clustering accuracy of Ensemble Clustering by employing heuristic optimisation techniques to achieve a robust combination of relevant information during the consensus clustering stage. Two novel heuristic optimisation-based Ensemble Clustering methods, Multi-Optimisation Consensus Clustering (MOCC) and K-Ants Consensus Clustering (KACC), are developed and introduced in this thesis. These methods utilise two heuristic optimisation algorithms (Simulated Annealing and Ant Colony Optimisation) for their Ensemble Clustering frameworks, and have been proved to outperform other methods in the area. The extensive experimental results, together with a detailed analysis, will be presented in this thesis