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34
Using Bayesian networks to analyze expression data
 Journal of Computational Biology
, 2000
"... DNA hybridization arrays simultaneously measure the expression level for thousands of genes. These measurements provide a “snapshot ” of transcription levels within the cell. A major challenge in computational biology is to uncover, from such measurements, gene/protein interactions and key biologica ..."
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Cited by 731 (16 self)
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DNA hybridization arrays simultaneously measure the expression level for thousands of genes. These measurements provide a “snapshot ” of transcription levels within the cell. A major challenge in computational biology is to uncover, from such measurements, gene/protein interactions and key biological features of cellular systems. In this paper, we propose a new framework for discovering interactions between genes based on multiple expression measurements. This framework builds on the use of Bayesian networks for representing statistical dependencies. A Bayesian network is a graphbased model of joint multivariate probability distributions that captures properties of conditional independence between variables. Such models are attractive for their ability to describe complex stochastic processes and because they provide a clear methodology for learning from (noisy) observations. We start by showing how Bayesian networks can describe interactions between genes. We then describe a method for recovering gene interactions from microarray data using tools for learning Bayesian networks. Finally, we demonstrate this method on the S. cerevisiae cellcycle measurements of Spellman et al. (1998). Key words: gene expression, microarrays, Bayesian methods. 1.
Being Bayesian about network structure
 Machine Learning
, 2000
"... Abstract. In many multivariate domains, we are interested in analyzing the dependency structure of the underlying distribution, e.g., whether two variables are in direct interaction. We can represent dependency structures using Bayesian network models. To analyze a given data set, Bayesian model sel ..."
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Cited by 202 (5 self)
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Abstract. In many multivariate domains, we are interested in analyzing the dependency structure of the underlying distribution, e.g., whether two variables are in direct interaction. We can represent dependency structures using Bayesian network models. To analyze a given data set, Bayesian model selection attempts to find the most likely (MAP) model, and uses its structure to answer these questions. However, when the amount of available data is modest, there might be many models that have nonnegligible posterior. Thus, we want compute the Bayesian posterior of a feature, i.e., the total posterior probability of all models that contain it. In this paper, we propose a new approach for this task. We first show how to efficiently compute a sum over the exponential number of networks that are consistent with a fixed order over network variables. This allows us to compute, for a given order, both the marginal probability of the data and the posterior of a feature. We then use this result as the basis for an algorithm that approximates the Bayesian posterior of a feature. Our approach uses a Markov Chain Monte Carlo (MCMC) method, but over orders rather than over network structures. The space of orders is smaller and more regular than the space of structures, and has much a smoother posterior “landscape”. We present empirical results on synthetic and reallife datasets that compare our approach to full model averaging (when possible), to MCMC over network structures, and to a nonBayesian bootstrap approach.
Inferring Subnetworks from Perturbed Expression Profiles
, 2001
"... Genomewide expression profiles of genetic mutants provide a wide variety of measurements of cellular responses to perturbations. Typical analysis of such data identifies genes affected by perturbation and uses clustering to group genes of similar function. In this paper we discover a finer structur ..."
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Cited by 159 (12 self)
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Genomewide expression profiles of genetic mutants provide a wide variety of measurements of cellular responses to perturbations. Typical analysis of such data identifies genes affected by perturbation and uses clustering to group genes of similar function. In this paper we discover a finer structure of interactions between genes, such as causality, mediation, activation, and inhibition by using a Bayesian network framework. We extend this framework to correctly handle perturbations, and to identify significant subnetworks of interacting genes. We apply this method to expression data of S. cerevisiae mutants and uncover a variety of structured metabolic, signaling and regulatory pathways. Contact: danab@cs.huji.ac.il
Modeling Dependencies in ProteinDNA Binding Sites
, 2003
"... The availability of whole genome sequences and highthroughput genomic assays opens the door for in silico analysis of transcription regulation. This includes methods for discovering and characterizing the binding sites of DNAbinding proteins, such as transcription factors. A common representation ..."
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Cited by 79 (2 self)
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The availability of whole genome sequences and highthroughput genomic assays opens the door for in silico analysis of transcription regulation. This includes methods for discovering and characterizing the binding sites of DNAbinding proteins, such as transcription factors. A common representation of transcription factor binding sites is aposition specific score matrix (PSSM). This representation makes the strong assumption that binding site positions are independent of each other. In this work, we explore Bayesian network representations of binding sites that provide different tradeoffs between complexity (number of parameters) and the richness of dependencies between positions. We develop the formal machinery for learning such models from data and for estimating the statistical significance of putative binding sites. We then evaluate the ramifications of these richer representations in characterizing binding site motifs and predicting their genomic locations. We show that these richer representations improve over the PSSM model in both tasks.
Learning Module Networks
, 2003
"... Methods for learning Bayesian networks can discover dependency structure between observed variables. Although these methods are useful in many applications, they run into computational and statistical problems in domains that involve a large number of variables. In this paper, we ..."
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Cited by 44 (4 self)
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Methods for learning Bayesian networks can discover dependency structure between observed variables. Although these methods are useful in many applications, they run into computational and statistical problems in domains that involve a large number of variables. In this paper, we
Discovering Hidden Variables: A StructureBased Approach
 IN NIPS
, 2001
"... A serious problem in learning probabilistic models is the presence of hidden variables. These variables are not observed, yet interact with several of the observed variables. As such, they induce seemingly complex dependencies among the latter. In recent years, much attention has been devoted t ..."
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Cited by 40 (5 self)
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A serious problem in learning probabilistic models is the presence of hidden variables. These variables are not observed, yet interact with several of the observed variables. As such, they induce seemingly complex dependencies among the latter. In recent years, much attention has been devoted to the development of algorithms for learning parameters, and in some cases structure, in the presence of hidden variables. In this paper, we address the related problem of detecting hidden variables that interact with the observed variables. This problem is of interest both for improving our understanding of the domain and as a preliminary step that guides the learning procedure towards promising models. A very natural approach is to search for "structural signatures" of hidden variables  substructures in the learned network that tend to suggest the presence of a hidden variable. We make this basic idea concrete, and show how to integrate it with structuresearch algorithms. We evaluate this method on several synthetic and reallife datasets, and show that it performs surprisingly well.
Time and Sample Efficient Discovery of Markov Blankets And Direct Causal Relations
 Proceedings of the 9th CAN SIGKDD International Conference on Knowledge Discovery and Data Mining
, 2003
"... Data Mining with Bayesian Network learning has two important characteristics: under broad conditions learned edges between variables correspond to causal influences, and second, for every variable T in the network a special subset (Markov Blanket) identifiable by the network is the mini mal variabl ..."
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Cited by 29 (7 self)
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Data Mining with Bayesian Network learning has two important characteristics: under broad conditions learned edges between variables correspond to causal influences, and second, for every variable T in the network a special subset (Markov Blanket) identifiable by the network is the mini mal variable set required to predict T. However, all known algorithms learning a complete BN do not scale up beyond a few hundred variables. On the other hand, all known sound algorithms learning a local region of the network require an exponential number of training instances to the size of the learned region.
R.: Inductive transfer for Bayesian network structure learning
 In: Proceedings of the 11th International Conference on AI and Statistics (AISTATS
, 2007
"... We consider the problem of learning Bayes Net structures for related tasks. We present an algorithm for learning Bayes Net structures that takes advantage of the similarity between tasks by biasing learning toward similar structures for each task. Heuristic search is used to find a high scoring set ..."
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Cited by 22 (1 self)
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We consider the problem of learning Bayes Net structures for related tasks. We present an algorithm for learning Bayes Net structures that takes advantage of the similarity between tasks by biasing learning toward similar structures for each task. Heuristic search is used to find a high scoring set of structures (one for each task), where the score for a set of structures is computed in a principled way. Experiments on problems generated from the ALARM and INSURANCE networks show that learning the structures for related tasks using the proposed method yields better results than learning the structures independently. 1
Bayesian Network Analysis of Signaling Networks: A Primer
, 2005
"... Highthroughput proteomic data can be used to reveal the connectivity of signaling networks and the influences between signaling molecules. We present a primer on the use of Bayesian networks for this task. Bayesian networks have been successfully used to derive causal influences among biological si ..."
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Cited by 21 (0 self)
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Highthroughput proteomic data can be used to reveal the connectivity of signaling networks and the influences between signaling molecules. We present a primer on the use of Bayesian networks for this task. Bayesian networks have been successfully used to derive causal influences among biological signaling molecules (for example, in the analysis of intracellular multicolor flow cytometry). We discuss ways to automatically derive a Bayesian network model from proteomic data and to interpret the resulting model.
Reconstruction of gene networks using Bayesian learning and manipulation experiments
 Bioinformatics
, 2004
"... learning and manipulation experiments ..."