A Sequence Similarity Search Algorithm Based on a Probabilistic Interpretation of an Alignment Scoring System

AAAI Conferences

We present a probabilistic interpretation of local sequence alignment methods where the alignment scoring system (ASS) plays the role of a stochastic process defining a probability distribution over all sequence pairs. An explicit algorithm is given to compute the probability of two sequences given an ASS. Based on this definition, a modified version of the Smith-Waterman local similarity search algorithm has been devised, which assesses sequence relationships by log likelihood ratios. When tested on classical example such as globins or G-protein-coupled receptors, the new method proved to be up to an order of magnitude more sensitive than the native Smith-Waterman algorithm. Introduction The comparison of a new protein sequence against a database of known proteins is perhaps the most important computer application in molecular sequence analysis.

On the Difficulty of Achieving Equilibrium in Interactive POMDPs

AAAI Conferences

We analyze the asymptotic behavior of agents engaged in an infinite horizon partially observable stochastic game as formalized by the interactive POMDP framework. We show that when agents' initial beliefs satisfy a truth compatibility condition, their behavior converges to a subjective ɛ-equilibrium in a finite time, and subjective equilibrium in the limit. This result is a generalization of a similar result in repeated games, to partially observable stochastic games. However, it turns out that the equilibrating process is difficult to demonstrate computationally because of the difficulty in coming up with initial beliefs that are both natural and satisfy the truth compatibility condition. Our results, therefore, shed some negative light on using equilibria as a solution concept for decision making in partially observable stochastic games.

RNA Modeling Using Gibbs Sampling and Stochastic Context Free Grammars

AAAI Conferences

Leslie Grate and Mark Herbster and Richard Hughey and David Haussler Baskin (;enter for Computer Engineering and Computer and Information Sciences University of California Santa Cruz, CA 95064 Keywords: RNA secondary structure, Gibbs sampler, Expectation Maximization, stochastic contextfree grammars, hidden Markov models, tP NA, snRNA, 16S rRNA, linguistic methods Abstract A new method of discovering the common secondary structure of a family of homologous RNA sequences using Gibbs sampling and stochastic context-free grammars is proposed. These parameters describe a statistical model of the family. After the Gibbs sampling has produced a crude statistical model for the family, this model is translated into a stochastic context-free grammar, which is then refined by an Expectation Maximization (EM) procedure produce a more complete model. A prototype implementation of the method is tested on tRNA, pieces of 16S rRNA and on U5 snRNA with good results. I. Saira Mian and Harry Noller Sinsheimer Laboratories University of California Santa Cruz, CA 95064 Introduction Tools for analyzing RNA are becoming increasingly important as in vitro evolution and selection techniques produce greater numbers of synthesized RNA families to supplement those related by phylogeny. Two principal methods have been established for predicting RNA secondary structure base pairings. The second technique employs thermodynamics to compare the free energy changes predicted for formation of possible s,'covdary structure and relies on finding the structure with the lowest free energy (Tinoco Jr., Uhlenbeck, & Levine 1971: Turner, Sugimoto, & Freier 1988; *This work was supported in part by NSF grants C,I)A-9115268 and IR1-9123692, and NIIt gratnt (.;M17129. When several related sequences are available that all share a common secondary structure, combinations of different approaches have been used to obtain improved results (Waterman 1989; Le & Zuker 1991; Han& Kim 1993; Chiu & Kolodziejczak 1991; Sankoff 1985; Winker et al. 1990; Lapedes 1992; Klinger & Brutlag 1993; Gutell et aL 1992). Recent efforts have applied Stochastic Context-Free Grammars (SCFGs) to the problems of statistical modeling, multiple alignment, discrimination and prediction of the secondary structure of RNA families (Sakakibara el al. 1994; 1993; Eddy & Durbin 1994; Searls 1993).

Neural Networks for Determining Protein Specificity and Multiple Alignment of Binding Sites

AAAI Conferences

Regulation of gene expression often involves proteins that bind to particular regions of DNA. Determining the binding sites for a protein and its specificity usually requires extensive biochemical and/or genetic experimentation. In this paper we illustrate the use of a neural network to obtain the desired information with much less experimental effort. It is often fairly easy to obtain a set of moderate length sequences, perhaps one or two hundred base-pairs, that each contain binding sites for the protein being studied. For example, the upstream regions of a set of genes that are all regulated by the same protein should each contain binding sites for that protein.

Joint Modeling of Multiple Related Time Series via the Beta Process

arXiv.org Machine Learning

We propose a Bayesian nonparametric approach to the problem of jointly modeling multiple related time series. Our approach is based on the discovery of a set of latent, shared dynamical behaviors. Using a beta process prior, the size of the set and the sharing pattern are both inferred from data. We develop efficient Markov chain Monte Carlo methods based on the Indian buffet process representation of the predictive distribution of the beta process, without relying on a truncated model. In particular, our approach uses the sum-product algorithm to efficiently compute Metropolis-Hastings acceptance probabilities, and explores new dynamical behaviors via birth and death proposals. We examine the benefits of our proposed feature-based model on several synthetic datasets, and also demonstrate promising results on unsupervised segmentation of visual motion capture data.