5,837 research outputs found
Testing statistical hypothesis on random trees and applications to the protein classification problem
Efficient automatic protein classification is of central importance in
genomic annotation. As an independent way to check the reliability of the
classification, we propose a statistical approach to test if two sets of
protein domain sequences coming from two families of the Pfam database are
significantly different. We model protein sequences as realizations of Variable
Length Markov Chains (VLMC) and we use the context trees as a signature of each
protein family. Our approach is based on a Kolmogorov--Smirnov-type
goodness-of-fit test proposed by Balding et al. [Limit theorems for sequences
of random trees (2008), DOI: 10.1007/s11749-008-0092-z]. The test statistic is
a supremum over the space of trees of a function of the two samples; its
computation grows, in principle, exponentially fast with the maximal number of
nodes of the potential trees. We show how to transform this problem into a
max-flow over a related graph which can be solved using a Ford--Fulkerson
algorithm in polynomial time on that number. We apply the test to 10 randomly
chosen protein domain families from the seed of Pfam-A database (high quality,
manually curated families). The test shows that the distributions of context
trees coming from different families are significantly different. We emphasize
that this is a novel mathematical approach to validate the automatic clustering
of sequences in any context. We also study the performance of the test via
simulations on Galton--Watson related processes.Comment: Published in at http://dx.doi.org/10.1214/08-AOAS218 the Annals of
Applied Statistics (http://www.imstat.org/aoas/) by the Institute of
Mathematical Statistics (http://www.imstat.org
Latent tree models
Latent tree models are graphical models defined on trees, in which only a
subset of variables is observed. They were first discussed by Judea Pearl as
tree-decomposable distributions to generalise star-decomposable distributions
such as the latent class model. Latent tree models, or their submodels, are
widely used in: phylogenetic analysis, network tomography, computer vision,
causal modeling, and data clustering. They also contain other well-known
classes of models like hidden Markov models, Brownian motion tree model, the
Ising model on a tree, and many popular models used in phylogenetics. This
article offers a concise introduction to the theory of latent tree models. We
emphasise the role of tree metrics in the structural description of this model
class, in designing learning algorithms, and in understanding fundamental
limits of what and when can be learned
Machine learning in the analysis of biomolecular simulations
Machine learning has rapidly become a key method for the analysis and organization of large-scale data in all scientific disciplines. In life sciences, the use of machine learning techniques is a particularly appealing idea since the enormous capacity of computational infrastructures generates terabytes of data through millisecond simulations of atomistic and molecular-scale biomolecular systems. Due to this explosion of data, the automation, reproducibility, and objectivity provided by machine learning methods are highly desirable features in the analysis of complex systems. In this review, we focus on the use of machine learning in biomolecular simulations. We discuss the main categories of machine learning tasks, such as dimensionality reduction, clustering, regression, and classification used in the analysis of simulation data. We then introduce the most popular classes of techniques involved in these tasks for the purpose of enhanced sampling, coordinate discovery, and structure prediction. Whenever possible, we explain the scope and limitations of machine learning approaches, and we discuss examples of applications of these techniques.Peer reviewe
Computational Molecular Biology
Computational Biology is a fairly new subject that arose in response to the computational problems posed by the analysis and the processing of biomolecular sequence and structure data. The field was initiated in the late 60's and early 70's largely by pioneers working in the life sciences. Physicists and mathematicians entered the field in the 70's and 80's, while Computer Science became involved with the new biological problems in the late 1980's. Computational problems have gained further importance in molecular biology through the various genome projects which produce enormous amounts of data. For this bibliography we focus on those areas of computational molecular biology that involve discrete algorithms or discrete optimization. We thus neglect several other areas of computational molecular biology, like most of the literature on the protein folding problem, as well as databases for molecular and genetic data, and genetic mapping algorithms. Due to the availability of review papers and a bibliography this bibliography
Nonlinear Models Using Dirichlet Process Mixtures
We introduce a new nonlinear model for classification, in which we model the
joint distribution of response variable, y, and covariates, x,
non-parametrically using Dirichlet process mixtures. We keep the relationship
between y and x linear within each component of the mixture. The overall
relationship becomes nonlinear if the mixture contains more than one component.
We use simulated data to compare the performance of this new approach to a
simple multinomial logit (MNL) model, an MNL model with quadratic terms, and a
decision tree model. We also evaluate our approach on a protein fold
classification problem, and find that our model provides substantial
improvement over previous methods, which were based on Neural Networks (NN) and
Support Vector Machines (SVM). Folding classes of protein have a hierarchical
structure. We extend our method to classification problems where a class
hierarchy is available. We find that using the prior information regarding the
hierarchical structure of protein folds can result in higher predictive
accuracy
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
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