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@article{Alexandersson2003SLAM, author = {Alexandersson, M. and Cawley, S. and Pachter, L.}, title = {S{LAM}: cross-species gene finding and alignment with a generalized pair hidden {M}arkov model.}, journal = {Genome {R}es.}, year = {2003}, volume = {13}, pages = {496--502}, number = {3}, month = {Mar}, abstract = {Comparative-based gene recognition is driven by the principle that conserved regions between related organisms are more likely than divergent regions to be coding. {W}e describe a probabilistic framework for gene structure and alignment that can be used to simultaneously find both the gene structure and alignment of two syntenic genomic regions. {A} key feature of the method is the ability to enhance gene predictions by finding the best alignment between two syntenic sequences, while at the same time finding biologically meaningful alignments that preserve the correspondence between coding exons. {O}ur probabilistic framework is the generalized pair hidden {M}arkov model, a hybrid of (1). generalized hidden {M}arkov models, which have been used previously for gene finding, and (2). pair hidden {M}arkov models, which have applications to sequence alignment. {W}e have built a gene finding and alignment program called {SLAM}, which aligns and identifies complete exon/intron structures of genes in two related but unannotated sequences of {DNA}. {SLAM} is able to reliably predict gene structures for any suitably related pair of organisms, most notably with fewer false-positive predictions compared to previous methods (examples are provided for {H}omo sapiens/{M}us musculus and {P}lasmodium falciparum/{P}lasmodium vivax comparisons). {A}ccuracy is obtained by distinguishing conserved noncoding sequence ({CNS}) from conserved coding sequence. {CNS} annotation is a novel feature of {SLAM} and may be useful for the annotation of {UTR}s, regulatory elements, and other noncoding features.}, doi = {10.1101/gr.424203}, pdf = {../local/Alexandersson2003SLAM.pdf}, file = {Alexandersson2003SLAM.pdf:local/Alexandersson2003SLAM.pdf:PDF}, keywords = {biogm}, owner = {vert}, pmid = {12618381}, timestamp = {2006.01.18}, url = {http://dx.doi.org/10.1101/gr.424203} }
@article{Beal2005Bayesian, author = {Beal, M. J. and Falciani, F. and Ghahramani, Z. and Rangel, C. and Wild, D. L.}, title = {A {B}ayesian approach to reconstructing genetic regulatory networks with hidden factors.}, journal = {Bioinformatics}, year = {2005}, volume = {21}, pages = {349--356}, number = {3}, month = {Feb}, abstract = {M{OTIVATION}: {W}e have used state-space models ({SSM}s) to reverse engineer transcriptional networks from highly replicated gene expression profiling time series data obtained from a well-established model of {T} cell activation. {SSM}s are a class of dynamic {B}ayesian networks in which the observed measurements depend on some hidden state variables that evolve according to {M}arkovian dynamics. {T}hese hidden variables can capture effects that cannot be directly measured in a gene expression profiling experiment, for example: genes that have not been included in the microarray, levels of regulatory proteins, the effects of m{RNA} and protein degradation, etc. {RESULTS}: {W}e have approached the problem of inferring the model structure of these state-space models using both classical and {B}ayesian methods. {I}n our previous work, a bootstrap procedure was used to derive classical confidence intervals for parameters representing 'gene-gene' interactions over time. {I}n this article, variational approximations are used to perform the analogous model selection task in the {B}ayesian context. {C}ertain interactions are present in both the classical and the {B}ayesian analyses of these regulatory networks. {T}he resulting models place {J}un{B} and {J}un{D} at the centre of the mechanisms that control apoptosis and proliferation. {T}hese mechanisms are key for clonal expansion and for controlling the long term behavior (e.g. programmed cell death) of these cells. {AVAILABILITY}: {S}upplementary data is available at http://public.kgi.edu/wild/index.htm and {M}atlab source code for variational {B}ayesian learning of {SSM}s is available at http://www.cse.ebuffalo.edu/faculty/mbeal/software.html.}, doi = {10.1093/bioinformatics/bti014}, pdf = {../local/Beal2005Bayesian.pdf}, file = {Beal2005Bayesian.pdf:local/Beal2005Bayesian.pdf:PDF}, keywords = {biogm}, owner = {vert}, pii = {bti014}, pmid = {15353451}, timestamp = {2006.01.18}, url = {http://dx.doi.org/10.1093/bioinformatics/bti014} }
@article{Engelhardt2005Protein, author = {Engelhardt, B. E. and Jordan, M. I. and Muratore, K. E. and Brenner, S. E.}, title = {Protein {M}olecular {F}unction {P}rediction by {B}ayesian {P}hylogenomics.}, journal = {P{L}o{S} {C}omput. {B}iol.}, year = {2005}, volume = {1}, pages = {e45}, number = {5}, month = {Oct}, abstract = {We present a statistical graphical model to infer specific molecular function for unannotated protein sequences using homology. {B}ased on phylogenomic principles, {SIFTER} ({S}tatistical {I}nference of {F}unction {T}hrough {E}volutionary {R}elationships) accurately predicts molecular function for members of a protein family given a reconciled phylogeny and available function annotations, even when the data are sparse or noisy. {O}ur method produced specific and consistent molecular function predictions across 100 {P}fam families in comparison to the {G}ene {O}ntology annotation database, {BLAST}, {GO}tcha, and {O}rthostrapper. {W}e performed a more detailed exploration of functional predictions on the adenosine-5'-monophosphate/adenosine deaminase family and the lactate/malate dehydrogenase family, in the former case comparing the predictions against a gold standard set of published functional characterizations. {G}iven function annotations for 3\% of the proteins in the deaminase family, {SIFTER} achieves 96\% accuracy in predicting molecular function for experimentally characterized proteins as reported in the literature. {T}he accuracy of {SIFTER} on this dataset is a significant improvement over other currently available methods such as {BLAST} (75\%), {G}ene{Q}uiz (64\%), {GO}tcha (89\%), and {O}rthostrapper (11\%). {W}e also experimentally characterized the adenosine deaminase from {P}lasmodium falciparum, confirming {SIFTER}'s prediction. {T}he results illustrate the predictive power of exploiting a statistical model of function evolution in phylogenomic problems. {A} software implementation of {SIFTER} is available from the authors.}, doi = {10.1371/journal.pcbi.0010045}, pdf = {../local/Engelhardt2005Protein.pdf}, file = {Engelhardt2005Protein.pdf:local/Engelhardt2005Protein.pdf:PDF}, keywords = {biogm}, owner = {vert}, pmid = {16217548}, timestamp = {2006.01.18}, url = {http://dx.doi.org/10.1371/journal.pcbi.0010045} }
@article{Friedman2000Using, author = {Friedman, N. and Linial, M. and Nachman, I. and Pe'er, D.}, title = {Using {B}ayesian Networks to Analyze Expression Data}, journal = {J. Comput. Biol.}, year = {2000}, volume = {7}, pages = {601--620}, number = {3-4}, abstract = {D{NA} hybridization arrays simultaneously measure the expression level for thousands of genes. {T}hese 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. {I}n this paper, we propose a new framework for discovering interactions between genes based on multiple expression measurements. {T}his framework builds on the use of {B}ayesian networks for representing statistical dependencies. {A} {B}ayesian network is a graph-based model of joint multivariate probability distributions that captures properties of conditional independence between variables. {S}uch models are attractive for their ability to describe complex stochastic processes and because they provide a clear methodology for learning from (noisy) observations. {W}e start by showing how {B}ayesian networks can describe interactions between genes. {W}e then describe a method for recovering gene interactions from microarray data using tools for learning {B}ayesian networks. {F}inally, we demonstrate this method on the {S}. cerevisiae cell-cycle measurements of {S}pellman et al. (1998).}, doi = {10.1089/106652700750050961}, pdf = {../local/Friedman2000Using.pdf}, file = {Friedman2000Using.pdf:local/Friedman2000Using.pdf:PDF}, keywords = {biogm}, subject = {microarray}, url = {http://dx.doi.org/10.1089/106652700750050961} }
@incollection{Heckerman1999tutorial, author = {Heckerman, D.}, title = {A tutorial on learning with {B}ayesian networks}, booktitle = {Learning in graphical models}, publisher = {MIT Press}, year = {1999}, editor = {Jordan, M.}, pages = {301--354}, address = {Cambridge, MA, USA}, pdf = {../local/Heckerman1999tutorial.pdf}, file = {Heckerman1999tutorial.pdf:local/Heckerman1999tutorial.pdf:PDF}, keywords = {biogm}, owner = {vert}, timestamp = {2006.01.18} }
@article{Imoto2002Estimation, author = {Imoto, S. and Goto, T. and Miyano, S.}, title = {Estimation of genetic networks and functional structures between genes by using {B}ayesian networks and nonparametric regression.}, journal = {Pac. {S}ymp. {B}iocomput.}, year = {2002}, pages = {175--186}, abstract = {We propose a new method for constructing genetic network from gene expression data by using {B}ayesian networks. {W}e use nonparametric regression for capturing nonlinear relationships between genes and derive a new criterion for choosing the network in general situations. {I}n a theoretical sense, our proposed theory and methodology include previous methods based on {B}ayes approach. {W}e applied the proposed method to the {S}. cerevisiae cell cycle data and showed the effectiveness of our method by comparing with previous methods.}, pdf = {../local/Imoto2002Estimation.pdf}, file = {Imoto2002Estimation.pdf:local/Imoto2002Estimation.pdf:PDF}, keywords = {biogm}, owner = {vert}, pmid = {11928473}, timestamp = {2006.02.16}, url = {http://helix-web.stanford.edu/psb02/imoto.pdf} }
@article{Imoto2003Bayesian, author = {Imoto, S. and Kim, S. and Goto, T. and Miyano, S. and Aburatani, S. and Tashiro, K. and Kuhara, S.}, title = {Bayesian network and nonparametric heteroscedastic regression for nonlinear modeling of genetic network.}, journal = {J. {B}ioinform. {C}omput. {B}iol.}, year = {2003}, volume = {1}, pages = {231--252}, number = {2}, month = {Jul}, abstract = {We propose a new statistical method for constructing a genetic network from microarray gene expression data by using a {B}ayesian network. {A}n essential point of {B}ayesian network construction is the estimation of the conditional distribution of each random variable. {W}e consider fitting nonparametric regression models with heterogeneous error variances to the microarray gene expression data to capture the nonlinear structures between genes. {S}electing the optimal graph, which gives the best representation of the system among genes, is still a problem to be solved. {W}e theoretically derive a new graph selection criterion from {B}ayes approach in general situations. {T}he proposed method includes previous methods based on {B}ayesian networks. {W}e demonstrate the effectiveness of the proposed method through the analysis of {S}accharomyces cerevisiae gene expression data newly obtained by disrupting 100 genes.}, doi = {10.1142/S0219720003000071}, pdf = {../local/Imoto2003Bayesian.pdf}, file = {Imoto2003Bayesian.pdf:local/Imoto2003Bayesian.pdf:PDF}, keywords = {biogm}, owner = {vert}, pii = {S0219720003000071}, pmid = {15290771}, timestamp = {2006.02.16}, url = {http://dx.doi.org/10.1142/S0219720003000071} }
@article{Imoto2002Bayesian, author = {Imoto, S. and Sunyong, K. and Goto, T. and Aburatani, S. and Tashiro, K. and Kuhara, S. and Miyano, S.}, title = {Bayesian network and nonparametric heteroscedastic regression for nonlinear modeling of genetic network.}, journal = {Proc. {IEEE} {C}omput. {S}oc. {B}ioinform. {C}onf.}, year = {2002}, volume = {1}, pages = {219--227}, abstract = {We propose a new statistical method for constructing genetic network from microarray gene expression data by using a {B}ayesian network. {A}n essential point of {B}ayesian network construction is in the estimation of the conditional distribution of each random variable. {W}e consider fitting nonparametric regression models with heterogeneous error variances to the microarray gene expression data to capture the nonlinear structures between genes. {A} problem still remains to be solved in selecting an optimal graph, which gives the best representation of the system among genes. {W}e theoretically derive a new graph selection criterion from {B}ayes approach in general situations. {T}he proposed method includes previous methods based on {B}ayesian networks. {W}e demonstrate the effectiveness of the proposed method through the analysis of {S}accharomyces cerevisiae gene expression data newly obtained by disrupting 100 genes.}, doi = {10.1109/CSB.2002.1039344}, pdf = {../local/Imoto2002Bayesian.pdf}, file = {Imoto2002Bayesian.pdf:local/Imoto2002Bayesian.pdf:PDF}, keywords = {biogm}, owner = {vert}, pmid = {15838138}, timestamp = {2006.02.16}, url = {http://dx.doi.org/10.1109/CSB.2002.1039344} }
@article{Jansen2003Bayesian, author = {Jansen, R. and Yu, H. and Greenbaum, D. and Kluger, Y. and Krogan, N.J. and Chung, S. and Emili, A. and Snyder, M. and Greenblatt, J.F. and Gerstein, M.}, title = {A {B}ayesian networks approach for predicting protein-protein interactions from genomic data}, journal = {Science}, year = {2003}, volume = {302}, pages = {449-453}, number = {5644}, abstract = {We have developed an approach using {B}ayesian networks to predict protein-protein interactions genome-wide in yeast. {O}ur method naturally weights and combines into reliable predictions genomic features only weakly associated with interaction (e.g., m{RNA} coexpression, coessentiality, and colocalization). {I}n addition to de novo predictions, it can integrate often noisy, experimental interaction data sets. {W}e observe that at given levels of sensitivity, our predictions are more accurate than the existing high-throughput experimental data sets. {W}e validate our predictions with new {TAP}?tagging (tandem affinity purification) experiments.}, doi = {10.1126/science.1087361}, pdf = {../local/Jansen2003Bayesian.pdf}, file = {Jansen2003Bayesian.pdf:local/Jansen2003Bayesian.pdf:PDF}, keywords = {biogm}, owner = {vert}, url = {http://dx.doi.org/10.1126/science.1087361} }
@article{Majoros2005Efficient, author = {Majoros, W. H. and Pertea, L. and Salzberg, S. L.}, title = {Efficient implementation of a generalized pair hidden {M}arkov model for comparative gene finding.}, journal = {Bioinformatics}, year = {2005}, volume = {21}, pages = {1782--1788}, number = {9}, month = {May}, abstract = {M{OTIVATION}: {T}he increased availability of genome sequences of closely related organisms has generated much interest in utilizing homology to improve the accuracy of gene prediction programs. {G}eneralized pair hidden {M}arkov models ({GPHMM}s) have been proposed as one means to address this need. {H}owever, all {GPHMM} implementations currently available are either closed-source or the details of their operation are not fully described in the literature, leaving a significant hurdle for others wishing to advance the state of the art in {GPHMM} design. {RESULTS}: {W}e have developed an open-source {GPHMM} gene finder, {TWAIN}, which performs very well on two related {A}spergillus species, {A}.fumigatus and {A}.nidulans, finding 89\% of the exons and predicting 74\% of the gene models exactly correctly in a test set of 147 conserved gene pairs. {W}e describe the implementation of this {GPHMM} and we explicitly address the assumptions and limitations of the system. {W}e suggest possible ways of relaxing those assumptions to improve the utility of the system without sacrificing efficiency beyond what is practical. {AVAILABILITY}: {A}vailable at http://www.tigr.org/software/pirate/twain/twain.html under the open-source {A}rtistic {L}icense.}, doi = {10.1093/bioinformatics/bti297}, pdf = {../local/Majoros2005Efficient.pdf}, file = {Majoros2005Efficient.pdf:local/Majoros2005Efficient.pdf:PDF}, keywords = {biogm}, owner = {vert}, pii = {bti297}, pmid = {15691859}, timestamp = {2006.01.18}, url = {http://dx.doi.org/10.1093/bioinformatics/bti297} }
@article{McAuliffe2004Multiple-sequence, author = {McAuliffe, J. D. and Pachter, L. and Jordan, M. I.}, title = {Multiple-sequence functional annotation and the generalized hidden {M}arkov phylogeny.}, journal = {Bioinformatics}, year = {2004}, volume = {20}, pages = {1850--1860}, number = {12}, month = {Aug}, abstract = {M{OTIVATION}: {P}hylogenetic shadowing is a comparative genomics principle that allows for the discovery of conserved regions in sequences from multiple closely related organisms. {W}e develop a formal probabilistic framework for combining phylogenetic shadowing with feature-based functional annotation methods. {T}he resulting model, a generalized hidden {M}arkov phylogeny ({GHMP}), applies to a variety of situations where functional regions are to be inferred from evolutionary constraints. {RESULTS}: {W}e show how {GHMP}s can be used to predict complete shared gene structures in multiple primate sequences. {W}e also describe shadower, our implementation of such a prediction system. {W}e find that shadower outperforms previously reported ab initio gene finders, including comparative human-mouse approaches, on a small sample of diverse exonic regions. {F}inally, we report on an empirical analysis of shadower's performance which reveals that as few as five well-chosen species may suffice to attain maximal sensitivity and specificity in exon demarcation. {AVAILABILITY}: {A} {W}eb server is available at http://bonaire.lbl.gov/shadower}, doi = {10.1093/bioinformatics/bth153}, pdf = {../local/McAuliffe2004Multiple-sequence.pdf}, file = {McAuliffe2004Multiple-sequence.pdf:local/McAuliffe2004Multiple-sequence.pdf:PDF}, keywords = {biogm}, owner = {vert}, pii = {bth153}, pmid = {14988105}, timestamp = {2006.01.18}, url = {http://dx.doi.org/10.1093/bioinformatics/bth153} }
@techreport{Murphy1999Modelling, author = {Murphy, K. and Mian, S.}, title = {Modelling gene expression data using dynamic {B}ayesian networks}, institution = {Computer Science Division, University of California, Berkeley, CA.}, year = {1999}, pdf = {../local/Murphy1999Modelling.pdf}, file = {Murphy1999Modelling.pdf:local/Murphy1999Modelling.pdf:PDF}, keywords = {biogm}, owner = {vert}, timestamp = {2006.01.18} }
@article{Segal2004module, author = {Segal, E. and Friedman, N. and Koller, D. and Regev, A.}, title = {A module map showing conditional activity of expression modules in cancer.}, journal = {Nat. {G}enet.}, year = {2004}, volume = {36}, pages = {1090--1098}, number = {10}, month = {Oct}, abstract = {D{NA} microarrays are widely used to study changes in gene expression in tumors, but such studies are typically system-specific and do not address the commonalities and variations between different types of tumor. {H}ere we present an integrated analysis of 1,975 published microarrays spanning 22 tumor types. {W}e describe expression profiles in different tumors in terms of the behavior of modules, sets of genes that act in concert to carry out a specific function. {U}sing a simple unified analysis, we extract modules and characterize gene-expression profiles in tumors as a combination of activated and deactivated modules. {A}ctivation of some modules is specific to particular types of tumor; for example, a growth-inhibitory module is specifically repressed in acute lymphoblastic leukemias and may underlie the deregulated proliferation in these cancers. {O}ther modules are shared across a diverse set of clinical conditions, suggestive of common tumor progression mechanisms. {F}or example, the bone osteoblastic module spans a variety of tumor types and includes both secreted growth factors and their receptors. {O}ur findings suggest that there is a single mechanism for both primary tumor proliferation and metastasis to bone. {O}ur analysis presents multiple research directions for diagnostic, prognostic and therapeutic studies.}, doi = {10.1038/ng1434}, pdf = {../local/Segal2004module.pdf}, file = {Segal2004module.pdf:local/Segal2004module.pdf:PDF}, keywords = {biogm}, owner = {vert}, pii = {ng1434}, pmid = {15448693}, timestamp = {2006.01.18}, url = {http://dx.doi.org/10.1038/ng1434} }
@article{Segal2003Module, author = {Segal, E. and Shapira, M. and Regev, A. and Pe'er, D. and Botstein, D. and Koller, D. and Friedman, N.}, title = {Module networks: identifying regulatory modules and their condition-specific regulators from gene expression data.}, journal = {Nat. {G}enet.}, year = {2003}, volume = {34}, pages = {166--176}, number = {2}, month = {Jun}, abstract = {Much of a cell's activity is organized as a network of interacting modules: sets of genes coregulated to respond to different conditions. {W}e present a probabilistic method for identifying regulatory modules from gene expression data. {O}ur procedure identifies modules of coregulated genes, their regulators and the conditions under which regulation occurs, generating testable hypotheses in the form 'regulator {X} regulates module {Y} under conditions {W}'. {W}e applied the method to a {S}accharomyces cerevisiae expression data set, showing its ability to identify functionally coherent modules and their correct regulators. {W}e present microarray experiments supporting three novel predictions, suggesting regulatory roles for previously uncharacterized proteins.}, doi = {10.1038/ng1165}, pdf = {../local/Segal2003Module.pdf}, file = {Segal2003Module.pdf:Segal2003Module.pdf:PDF}, keywords = {biogm}, owner = {vert}, pii = {ng1165}, pmid = {12740579}, timestamp = {2006.01.18}, url = {http://dx.doi.org/10.1038/ng1165} }
@article{Xing2004LOGOS, author = {Xing, E. P. and Wu, W. and Jordan, M. I. and Karp, R. M.}, title = {L{OGOS}: {A} modular {B}ayesian model for de novo motif detection}, journal = {J. {B}ioinform. {C}omput. {B}iol.}, year = {2004}, volume = {2}, pages = {127--154}, abstract = {The complexity of the global organization and internal structure of motifs in higher eukaryotic organisms raises significant challenges for motif detection techniques. {T}o achieve successful de novo motif detection, it is necessary to model the complex dependencies within and among motifs and to incorporate biological prior knowledge. {I}n this paper, we present {LOGOS}, an integrated {LO}cal and {G}l{O}bal motif {S}equence model for biopolymer sequences, which provides a principled framework for developing, modularizing, extending and computing expressive motif models for complex biopolymer sequence analysis. {LOGOS} consists of two interacting submodels: {HMDM}, a local alignment model capturing biological prior knowledge and positional dependency within the motif local structure; and {HMM}, a global motif distribution model modeling frequencies and dependencies of motif occurrences. {M}odel parameters can be fit using training motifs within an empirical {B}ayesian framework. {A} variational {EM} algorithm is developed for de novo motif detection. {LOGOS} improves over existing models that ignore biological priors and dependencies in motif structures and motif occurrences, and demonstrates superior performance on both semi-realistic test data and cis-regulatory sequences from yeast and {D}rosophila genomes with regard to sensitivity, specificity, flexibility and extensibility.}, doi = {10.1142/S0219720004000508}, pdf = {../local/Xing2004LOGOS.pdf}, file = {Xing2004LOGOS.pdf:Xing2004LOGOS.pdf:PDF}, keywords = {biogm}, owner = {vert}, timestamp = {2006.01.18}, url = {http://dx.doi.org/10.1142/S0219720004000508} }
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