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Alexander J. Hartemink

Professor of Computer Science
Computer Science
Box 90129, Durham, NC 27708-0129
308 Research Drive, LSRC D239, Durham, NC 27708-0129

Selected Publications


Single-cell multi-ome regression models identify functional and disease-associated enhancers and enable chromatin potential analysis.

Journal Article Nature genetics · April 2024 We present a gene-level regulatory model, single-cell ATAC + RNA linking (SCARlink), which predicts single-cell gene expression and links enhancers to target genes using multi-ome (scRNA-seq and scATAC-seq co-assay) sequencing data. The approach uses regul ... Full text Cite

Spatiotemporal kinetics of CAF-1-dependent chromatin maturation ensures transcription fidelity during S-phase.

Journal Article Genome Res · December 11, 2023 Proper maintenance of epigenetic information after replication is dependent on the rapid assembly and maturation of chromatin. Chromatin Assembly Complex 1 (CAF-1) is a conserved histone chaperone that deposits (H3-H4)2 tetramers as part of the replication ... Full text Link to item Cite

Profiling the quantitative occupancy of myriad transcription factors across conditions by modeling chromatin accessibility data.

Journal Article Genome Res · June 2022 Over a thousand different transcription factors (TFs) bind with varying occupancy across the human genome. Chromatin immunoprecipitation (ChIP) can assay occupancy genome-wide, but only one TF at a time, limiting our ability to comprehensively observe the ... Full text Link to item Cite

Cell-Cycle-Dependent Chromatin Dynamics at Replication Origins.

Journal Article Genes (Basel) · December 16, 2021 Origins of DNA replication are specified by the ordered recruitment of replication factors in a cell-cycle-dependent manner. The assembly of the pre-replicative complex in G1 and the pre-initiation complex prior to activation in S phase are well characteri ... Full text Link to item Cite

Cell cycle-dependent chromatin dynamics at replication origins

Journal Article · November 18, 2021 ABSTRACTOrigins of DNA replication are specified by the ordered recruitment of replication factors in a cell cycle dependent manner. The assembly of the pre-replicative complex in G1 and the pre-initiation complex prior to ... Full text Cite

RoboCOP: jointly computing chromatin occupancy profiles for numerous factors from chromatin accessibility data.

Journal Article Nucleic Acids Res · August 20, 2021 Chromatin is a tightly packaged structure of DNA and protein within the nucleus of a cell. The arrangement of different protein complexes along the DNA modulates and is modulated by gene expression. Measuring the binding locations and occupancy levels of d ... Full text Link to item Cite

Linking the dynamics of chromatin occupancy and transcription with predictive models.

Journal Article Genome Res · June 2021 Though the sequence of the genome within each eukaryotic cell is essentially fixed, it exists within a complex and changing chromatin state. This state is determined, in part, by the dynamic binding of proteins to the DNA. These proteins-including histones ... Full text Link to item Cite

Local nucleosome dynamics and eviction following a double-strand break are reversible by NHEJ-mediated repair in the absence of DNA replication.

Journal Article Genome Res · May 2021 We interrogated at nucleotide resolution the spatiotemporal order of chromatin changes that occur immediately following a site-specific double-strand break (DSB) upstream of the PHO5 locus and its subsequent repair by nonhomologous end joining (NHEJ). We o ... Full text Link to item Cite

Linking the dynamics of chromatin occupancy and transcription with predictive models

Journal Article · June 29, 2020 AbstractThough the sequence of the genome within each eukaryotic cell is essentially fixed, it exists within a complex and changing chromatin state. This state is determined, in part, by the dynamic binding of proteins to t ... Full text Cite

Quantitative occupancy of myriad transcription factors from one DNase experiment enables efficient comparisons across conditions

Journal Article · June 29, 2020 AbstractOver a thousand different transcription factors (TFs) bind with varying occupancy across the human genome. Chromatin immunoprecipitation (ChIP) can assay occupancy genome-wide, but only one TF at a time, limiting ou ... Full text Cite

RoboCOP: Jointly computing chromatin occupancy profiles for numerous factors from chromatin accessibility data

Journal Article · June 4, 2020 AbstractChromatin is the tightly packaged structure of DNA and protein within the nucleus of a cell. The arrangement of different protein complexes along the DNA modulates and is modulated by gene expression. Measuring the ... Full text Cite

RoboCOP: Multivariate State Space Model Integrating Epigenomic Accessibility Data to Elucidate Genome-Wide Chromatin Occupancy.

Conference Res Comput Mol Biol · May 2020 Chromatin is the tightly packaged structure of DNA and protein within the nucleus of a cell. The arrangement of different protein complexes along the DNA modulates and is modulated by gene expression. Measuring the binding locations and level of occupancy ... Full text Link to item Cite

Data from: RoboCOP: Multivariate state space model integrating epigenomic accessibility data to elucidate genome-wide chromatin occupancy

Dataset · January 24, 2020 RoboCOP (Robotic Chromatin Occupancy Profile) is a state space model that incorporates chromatin accessibility data and nucleotide sequence to predict nucleosome positions and transcription factor binding sites. In this paper, we generated the binding prof ... Full text Cite

Local nucleosome dynamics and eviction following a double-strand break are reversible by NHEJ-mediated repair in the absence of DNA replication

Journal Article · December 6, 2019 AbstractAlthough the molecular events required for the repair of double-strand breaks (DSB) have been well characterized, the role of epigenetic processes in the recognition and repair of DSBs has only been investigated at ... Full text Cite

Glucocorticoid receptor recruits to enhancers and drives activation by motif-directed binding.

Journal Article Genome Res · September 2018 Glucocorticoids are potent steroid hormones that regulate immunity and metabolism by activating the transcription factor (TF) activity of glucocorticoid receptor (GR). Previous models have proposed that DNA binding motifs and sites of chromatin accessibili ... Full text Link to item Cite

MATCHER: manifold alignment reveals correspondence between single cell transcriptome and epigenome dynamics.

Journal Article Genome Biol · July 24, 2017 Single cell experimental techniques reveal transcriptomic and epigenetic heterogeneity among cells, but how these are related is unclear. We present MATCHER, an approach for integrating multiple types of single cell measurements. MATCHER uses manifold alig ... Full text Link to item Cite

Single-cell multi-ome regression models identify functional and disease-associated enhancers and enable chromatin potential analysis.

Journal Article Nature genetics · April 2024 We present a gene-level regulatory model, single-cell ATAC + RNA linking (SCARlink), which predicts single-cell gene expression and links enhancers to target genes using multi-ome (scRNA-seq and scATAC-seq co-assay) sequencing data. The approach uses regul ... Full text Cite

Spatiotemporal kinetics of CAF-1-dependent chromatin maturation ensures transcription fidelity during S-phase.

Journal Article Genome Res · December 11, 2023 Proper maintenance of epigenetic information after replication is dependent on the rapid assembly and maturation of chromatin. Chromatin Assembly Complex 1 (CAF-1) is a conserved histone chaperone that deposits (H3-H4)2 tetramers as part of the replication ... Full text Link to item Cite

Profiling the quantitative occupancy of myriad transcription factors across conditions by modeling chromatin accessibility data.

Journal Article Genome Res · June 2022 Over a thousand different transcription factors (TFs) bind with varying occupancy across the human genome. Chromatin immunoprecipitation (ChIP) can assay occupancy genome-wide, but only one TF at a time, limiting our ability to comprehensively observe the ... Full text Link to item Cite

Cell-Cycle-Dependent Chromatin Dynamics at Replication Origins.

Journal Article Genes (Basel) · December 16, 2021 Origins of DNA replication are specified by the ordered recruitment of replication factors in a cell-cycle-dependent manner. The assembly of the pre-replicative complex in G1 and the pre-initiation complex prior to activation in S phase are well characteri ... Full text Link to item Cite

Cell cycle-dependent chromatin dynamics at replication origins

Journal Article · November 18, 2021 ABSTRACTOrigins of DNA replication are specified by the ordered recruitment of replication factors in a cell cycle dependent manner. The assembly of the pre-replicative complex in G1 and the pre-initiation complex prior to ... Full text Cite

RoboCOP: jointly computing chromatin occupancy profiles for numerous factors from chromatin accessibility data.

Journal Article Nucleic Acids Res · August 20, 2021 Chromatin is a tightly packaged structure of DNA and protein within the nucleus of a cell. The arrangement of different protein complexes along the DNA modulates and is modulated by gene expression. Measuring the binding locations and occupancy levels of d ... Full text Link to item Cite

Linking the dynamics of chromatin occupancy and transcription with predictive models.

Journal Article Genome Res · June 2021 Though the sequence of the genome within each eukaryotic cell is essentially fixed, it exists within a complex and changing chromatin state. This state is determined, in part, by the dynamic binding of proteins to the DNA. These proteins-including histones ... Full text Link to item Cite

Local nucleosome dynamics and eviction following a double-strand break are reversible by NHEJ-mediated repair in the absence of DNA replication.

Journal Article Genome Res · May 2021 We interrogated at nucleotide resolution the spatiotemporal order of chromatin changes that occur immediately following a site-specific double-strand break (DSB) upstream of the PHO5 locus and its subsequent repair by nonhomologous end joining (NHEJ). We o ... Full text Link to item Cite

Linking the dynamics of chromatin occupancy and transcription with predictive models

Journal Article · June 29, 2020 AbstractThough the sequence of the genome within each eukaryotic cell is essentially fixed, it exists within a complex and changing chromatin state. This state is determined, in part, by the dynamic binding of proteins to t ... Full text Cite

Quantitative occupancy of myriad transcription factors from one DNase experiment enables efficient comparisons across conditions

Journal Article · June 29, 2020 AbstractOver a thousand different transcription factors (TFs) bind with varying occupancy across the human genome. Chromatin immunoprecipitation (ChIP) can assay occupancy genome-wide, but only one TF at a time, limiting ou ... Full text Cite

RoboCOP: Jointly computing chromatin occupancy profiles for numerous factors from chromatin accessibility data

Journal Article · June 4, 2020 AbstractChromatin is the tightly packaged structure of DNA and protein within the nucleus of a cell. The arrangement of different protein complexes along the DNA modulates and is modulated by gene expression. Measuring the ... Full text Cite

RoboCOP: Multivariate State Space Model Integrating Epigenomic Accessibility Data to Elucidate Genome-Wide Chromatin Occupancy.

Conference Res Comput Mol Biol · May 2020 Chromatin is the tightly packaged structure of DNA and protein within the nucleus of a cell. The arrangement of different protein complexes along the DNA modulates and is modulated by gene expression. Measuring the binding locations and level of occupancy ... Full text Link to item Cite

Data from: RoboCOP: Multivariate state space model integrating epigenomic accessibility data to elucidate genome-wide chromatin occupancy

Dataset · January 24, 2020 RoboCOP (Robotic Chromatin Occupancy Profile) is a state space model that incorporates chromatin accessibility data and nucleotide sequence to predict nucleosome positions and transcription factor binding sites. In this paper, we generated the binding prof ... Full text Cite

Local nucleosome dynamics and eviction following a double-strand break are reversible by NHEJ-mediated repair in the absence of DNA replication

Journal Article · December 6, 2019 AbstractAlthough the molecular events required for the repair of double-strand breaks (DSB) have been well characterized, the role of epigenetic processes in the recognition and repair of DSBs has only been investigated at ... Full text Cite

Glucocorticoid receptor recruits to enhancers and drives activation by motif-directed binding.

Journal Article Genome Res · September 2018 Glucocorticoids are potent steroid hormones that regulate immunity and metabolism by activating the transcription factor (TF) activity of glucocorticoid receptor (GR). Previous models have proposed that DNA binding motifs and sites of chromatin accessibili ... Full text Link to item Cite

MATCHER: manifold alignment reveals correspondence between single cell transcriptome and epigenome dynamics.

Journal Article Genome Biol · July 24, 2017 Single cell experimental techniques reveal transcriptomic and epigenetic heterogeneity among cells, but how these are related is unclear. We present MATCHER, an approach for integrating multiple types of single cell measurements. MATCHER uses manifold alig ... Full text Link to item Cite

Manifold alignment reveals correspondence between single cell transcriptome and epigenome dynamics

Journal Article · April 24, 2017 AbstractSingle cell genomic techniques promise to yield key insights into the dynamic interplay between gene expression and epigenetic modification. However, the experimental difficulty of performing multiple measurements o ... Full text Cite

Characterization of dependencies between growth and division in budding yeast.

Journal Article J R Soc Interface · February 2017 Cell growth and division are processes vital to the proliferation and development of life. Coordination between these two processes has been recognized for decades in a variety of organisms. In the budding yeast Saccharomyces cerevisiae, this coordination ... Full text Link to item Cite

E pluribus unum: United states of single cells

Conference Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) · January 1, 2017 Cite

Establishment of Expression in the SHORTROOT-SCARECROW Transcriptional Cascade through Opposing Activities of Both Activators and Repressors.

Journal Article Dev Cell · December 5, 2016 Tissue-specific gene expression is often thought to arise from spatially restricted transcriptional cascades. However, it is unclear how expression is established at the top of these cascades in the absence of pre-existing specificity. We generated a trans ... Full text Link to item Cite

SLICER: inferring branched, nonlinear cellular trajectories from single cell RNA-seq data.

Journal Article Genome Biol · May 23, 2016 Single cell experiments provide an unprecedented opportunity to reconstruct a sequence of changes in a biological process from individual "snapshots" of cells. However, nonlinear gene expression changes, genes unrelated to the process, and the possibility ... Full text Open Access Link to item Cite

Mapping nucleosome positions using DNase-seq.

Journal Article Genome Res · March 2016 Although deoxyribonuclease I (DNase I) was used to probe the structure of the nucleosome in the 1960s and 1970s, in the current high-throughput sequencing era, DNase I has mainly been used to study genomic regions devoid of nucleosomes. Here, we reveal for ... Full text Link to item Cite

Genome-wide chromatin footprinting reveals changes in replication origin architecture induced by pre-RC assembly.

Journal Article Genes Dev · January 15, 2015 Start sites of DNA replication are marked by the origin recognition complex (ORC), which coordinates Mcm2-7 helicase loading to form the prereplicative complex (pre-RC). Although pre-RC assembly is well characterized in vitro, the process is poorly underst ... Full text Link to item Cite

Convergent transcriptional specializations in the brains of humans and song-learning birds.

Journal Article Science · December 12, 2014 Song-learning birds and humans share independently evolved similarities in brain pathways for vocal learning that are essential for song and speech and are not found in most other species. Comparisons of brain transcriptomes of song-learning birds and huma ... Full text Open Access Link to item Cite

Core and region-enriched networks of behaviorally regulated genes and the singing genome.

Journal Article Science · December 12, 2014 Songbirds represent an important model organism for elucidating molecular mechanisms that link genes with complex behaviors, in part because they have discrete vocal learning circuits that have parallels with those that mediate human speech. We found that ... Full text Open Access Link to item Cite

Learning protein-DNA interaction landscapes by integrating experimental data through computational models.

Journal Article Bioinformatics · October 15, 2014 MOTIVATION: Transcriptional regulation is directly enacted by the interactions between DNA and many proteins, including transcription factors (TFs), nucleosomes and polymerases. A critical step in deciphering transcriptional regulation is to infer, and eve ... Full text Link to item Cite

Inferring gene expression from ribosomal promoter sequences, a crowdsourcing approach.

Journal Article Genome Res · November 2013 The Gene Promoter Expression Prediction challenge consisted of predicting gene expression from promoter sequences in a previously unknown experimentally generated data set. The challenge was presented to the community in the framework of the sixth Dialogue ... Full text Link to item Cite

Stability selection for regression-based models of transcription factor-DNA binding specificity.

Journal Article Bioinformatics · July 1, 2013 MOTIVATION: The DNA binding specificity of a transcription factor (TF) is typically represented using a position weight matrix model, which implicitly assumes that individual bases in a TF binding site contribute independently to the binding affinity, an a ... Full text Open Access Link to item Cite

Synergistic and tunable human gene activation by combinations of synthetic transcription factors.

Journal Article Nat Methods · March 2013 Mammalian genes are regulated by the cooperative and synergistic actions of many transcription factors. In this study we recapitulate this complex regulation in human cells by targeting endogenous gene promoters, including regions of closed chromatin upstr ... Full text Link to item Cite

Branching process deconvolution algorithm reveals a detailed cell-cycle transcription program.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · March 2013 Due to cell-to-cell variability and asymmetric cell division, cells in a synchronized population lose synchrony over time. As a result, time-series measurements from synchronized cell populations do not reflect the underlying dynamics of cell-cycle process ... Full text Cite

Using DNase digestion data to accurately identify transcription factor binding sites.

Journal Article Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing · January 2013 Identifying binding sites of transcription factors (TFs) is a key task in deciphering transcriptional regulation. ChIP-based methods are used to survey the genomic locations of a single TF in each experiment. But methods combining DNase digestion data with ... Cite

Cell-cycle phenotyping with conditional random fields: A case study in Saccharomyces cerevisiae

Conference Proceedings - International Symposium on Biomedical Imaging · January 1, 2013 High-resolution, multimodal microscopy grants an intimate view of the inner workings of cells. Complex processes like cell division can be monitored with microscope images, assuming identification of cells and their cell-cycle markers: cellular structures ... Full text Cite

ChIP-seq guidelines and practices of the ENCODE and modENCODE consortia.

Journal Article Genome Res · September 2012 Chromatin immunoprecipitation (ChIP) followed by high-throughput DNA sequencing (ChIP-seq) has become a valuable and widely used approach for mapping the genomic location of transcription-factor binding and histone modifications in living cells. Despite it ... Full text Link to item Cite

Close Encounters of the Collaborative Kind

Journal Article Computer · March 2012 Full text Cite

Intrinsic disorder within and flanking the DNA-binding domains of human transcription factors.

Journal Article Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing · January 2012 While the term 'protein structure' is commonplace, it is increasingly appreciated that proteins may not possess a single, well-defined structure: some regions of proteins are intrinsically disordered. The role these intrinsically disordered regions (IDRs) ... Cite

A generalized model for multi-marker analysis of cell cycle progression in synchrony experiments.

Journal Article Bioinformatics (Oxford, England) · July 2011 MotivationTo advance understanding of eukaryotic cell division, it is important to observe the process precisely. To this end, researchers monitor changes in dividing cells as they traverse the cell cycle, with the presence or absence of morpholog ... Full text Cite

Identification of Tat-SF1 cellular targets by exon array analysis reveals dual roles in transcription and splicing.

Journal Article RNA · April 2011 Tat specific factor 1 (Tat-SF1) interacts with components of both the transcription and splicing machineries and has been classified as a transcription-splicing factor. Although its function as an HIV-1 dependency factor has been investigated, relatively l ... Full text Link to item Cite

Learning non-stationary dynamic bayesian networks

Journal Article Journal of Machine Learning Research · December 1, 2010 Learning dynamic Bayesian network structures provides a principled mechanism for identifying conditional dependencies in time-series data. An important assumption of traditional DBN structure learning is that the data are generated by a stationary process, ... Cite

Finding regulatory DNA motifs using alignment-free evolutionary conservation information.

Journal Article Nucleic Acids Res · April 2010 As an increasing number of eukaryotic genomes are being sequenced, comparative studies aimed at detecting regulatory elements in intergenic sequences are becoming more prevalent. Most comparative methods for transcription factor (TF) binding site discovery ... Full text Open Access Link to item Cite

Drosophila ORC localizes to open chromatin and marks sites of cohesin complex loading.

Journal Article Genome Res · February 2010 The origin recognition complex (ORC) is an essential DNA replication initiation factor conserved in all eukaryotes. In Saccharomyces cerevisiae, ORC binds to specific DNA elements; however, in higher eukaryotes, ORC exhibits little sequence specificity in ... Full text Link to item Cite

Finding regulatory DNA motifs using alignment-free evolutionary conservation information

Journal Article Nucleic Acids Research · January 4, 2010 As an increasing number of eukaryotic genomes are being sequenced, comparative studies aimed at detecting regulatory elements in intergenic sequences are becoming more prevalent. Most comparative methods for transcription factor (TF) binding site discovery ... Full text Cite

Distinguishing Direct versus Indirect Transcription Factor-DNA Interactions

Conference RESEARCH IN COMPUTATIONAL MOLECULAR BIOLOGY, PROCEEDINGS · January 1, 2010 Link to item Cite

Distinguishing direct versus indirect transcription factor-DNA interactions.

Journal Article Genome Res · November 2009 Transcriptional regulation is largely enacted by transcription factors (TFs) binding DNA. Large numbers of TF binding motifs have been revealed by ChIP-chip experiments followed by computational DNA motif discovery. However, the success of motif discovery ... Full text Link to item Cite

An ensemble model of competitive multi-factor binding of the genome.

Journal Article Genome research · November 2009 Hundreds of different factors adorn the eukaryotic genome, binding to it in large number. These DNA binding factors (DBFs) include nucleosomes, transcription factors (TFs), and other proteins and protein complexes, such as the origin recognition complex (O ... Full text Cite

Domain-oriented edge-based alignment of protein interaction networks.

Journal Article Bioinformatics (Oxford, England) · June 2009 MotivationRecent advances in high-throughput experimental techniques have yielded a large amount of data on protein-protein interactions (PPIs). Since these interactions can be organized into networks, and since separate PPI networks can be constr ... Full text Open Access Cite

A branching process model for flow cytometry and budding index measurements in cell synchrony experiments.

Journal Article The annals of applied statistics · January 2009 We present a flexible branching process model for cell population dynamics in synchrony/time-series experiments used to study important cellular processes. Its formulation is constructive, based on an accounting of the unique cohorts in the population as t ... Full text Open Access Cite

Non-stationary dynamic Bayesian networks

Journal Article Advances in Neural Information Processing Systems 21 - Proceedings of the 2008 Conference · January 1, 2009 A principled mechanism for identifying conditional dependencies in time-series data is provided through structure learning of dynamic Bayesian networks (DBNs). An important assumption of DBN structure learning is that the data are generated by a stationary ... Cite

Global control of cell-cycle transcription by coupled CDK and network oscillators.

Journal Article Nature · June 2008 A significant fraction of the Saccharomyces cerevisiae genome is transcribed periodically during the cell division cycle, indicating that properly timed gene expression is important for regulating cell-cycle events. Genomic analyses of the localization and ... Full text Cite

Using DNA duplex stability information for transcription factor binding site discovery.

Conference Pac Symp Biocomput · 2008 Transcription factor (TF) binding site discovery is an important step in understanding transcriptional regulation. Many computational tools have already been developed, but their success in detecting TF motifs is still limited. We believe one of the main r ... Link to item Cite

Computational and experimental identification of novel human imprinted genes.

Journal Article Genome Res · December 2007 Imprinted genes are essential in embryonic development, and imprinting dysregulation contributes to human disease. We report two new human imprinted genes: KCNK9 is predominantly expressed in the brain, is a known oncogene, and may be involved in bipolar d ... Full text Link to item Cite

A nucleosome-guided map of transcription factor binding sites in yeast.

Journal Article PLoS Comput Biol · November 2007 Finding functional DNA binding sites of transcription factors (TFs) throughout the genome is a crucial step in understanding transcriptional regulation. Unfortunately, these binding sites are typically short and degenerate, posing a significant statistical ... Full text Open Access Link to item Cite

A probabilistic model for cell cycle distributions in synchrony experiments.

Journal Article Cell cycle (Georgetown, Tex.) · February 2007 Synchronized populations of cells are often used to study dynamic processes during the cell division cycle. However, the analysis of time series measurements made on synchronized populations is confounded by the fact that populations lose synchrony over ti ... Full text Cite

Computational inference of neural information flow networks.

Journal Article PLoS Comput Biol · November 24, 2006 Determining how information flows along anatomical brain pathways is a fundamental requirement for understanding how animals perceive their environments, learn, and behave. Attempts to reveal such neural information flow have been made using linear computa ... Full text Open Access Link to item Cite

Informative priors based on transcription factor structural class improve de novo motif discovery.

Journal Article Bioinformatics · July 15, 2006 MOTIVATION: An important problem in molecular biology is to identify the locations at which a transcription factor (TF) binds to DNA, given a set of DNA sequences believed to be bound by that TF. In previous work, we showed that information in the DNA sequ ... Full text Link to item Cite

Finding diagnostic biomarkers in proteomic spectra.

Conference Pac Symp Biocomput · 2006 In seeking to find diagnostic biomarkers in proteomic spectra, two significant problems arise. First, not only is there noise in the measured intensity at each m/z value, but there is also noise in the measured m/z value itself. Second, the potential for o ... Link to item Cite

Sequence features of DNA binding sites reveal structural class of associated transcription factor.

Journal Article Bioinformatics (Oxford, England) · January 2006 MotivationA key goal in molecular biology is to understand the mechanisms by which a cell regulates the transcription of its genes. One important aspect of this transcriptional regulation is the binding of transcription factors (TFs) to their spec ... Full text Cite

Sparse multinomial logistic regression: fast algorithms and generalization bounds.

Journal Article IEEE transactions on pattern analysis and machine intelligence · June 2005 Recently developed methods for learning sparse classifiers are among the state-of-the-art in supervised learning. These methods learn classifiers that incorporate weighted sums of basis functions with sparsity-promoting priors encouraging the weight estima ... Full text Cite

Genome-wide prediction of imprinted murine genes.

Journal Article Genome research · June 2005 Imprinted genes are epigenetically modified genes whose expression is determined according to their parent of origin. They are involved in embryonic development, and imprinting dysregulation is linked to cancer, obesity, diabetes, and behavioral disorders ... Full text Cite

Reverse engineering gene regulatory networks.

Journal Article Nature biotechnology · May 2005 Full text Cite

Theoretical and practical advances in genome halving.

Journal Article Bioinformatics (Oxford, England) · April 2005 MotivationDuplication of an organism's entire genome is a rare but spectacular event, enabling the rapid emergence of multiple new gene functions. Over time, the parallel linkage of duplicated genes across chromosomes may be disrupted by reciproca ... Full text Cite

Informative structure priors: joint learning of dynamic regulatory networks from multiple types of data.

Conference Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing · January 2005 We present a method for jointly learning dynamic models of transcriptional regulatory networks from gene expression data and transcription factor binding location data. Models are automatically learned using dynamic Bayesian network inference algorithms; j ... Cite

On semi-supervised classification

Conference Advances in Neural Information Processing Systems · January 1, 2005 A graph-based prior is proposed for parametric semi-supervised classification. The prior utilizes both labelled and unlabelled data; it also integrates features from multiple views of a given sample (e.g., multiple sensors), thus implementing a Bayesian fo ... Cite

Advances to Bayesian network inference for generating causal networks from observational biological data.

Journal Article Bioinformatics · December 12, 2004 MOTIVATION: Network inference algorithms are powerful computational tools for identifying putative causal interactions among variables from observational data. Bayesian network inference algorithms hold particular promise in that they can capture linear, n ... Full text Open Access Link to item Cite

A Bayesian approach to joint feature selection and classifier design.

Journal Article IEEE transactions on pattern analysis and machine intelligence · September 2004 This paper adopts a Bayesian approach to simultaneously learn both an optimal nonlinear classifier and a subset of predictor variables (or features) that are most relevant to the classification task. The approach uses heavy-tailed priors to promote sparsit ... Full text Cite

Joint classifier and feature optimization for comprehensive cancer diagnosis using gene expression data.

Journal Article Journal of computational biology : a journal of computational molecular cell biology · January 2004 Recent research has demonstrated quite convincingly that accurate cancer diagnosis can be achieved by constructing classifiers that are designed to compare the gene expression profile of a tissue of unknown cancer status to a database of stored expression ... Full text Cite

Identification of differentially expressed proteins using MALDI-TOF mass spectra

Conference Conference Record of the Asilomar Conference on Signals, Systems and Computers · December 1, 2003 In the search for diagnostic and therapeutic strategies for lung cancer, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been evinced as a new and promising discovery platform to generate protein expression p ... Cite

Influence of network topology and data collection on network inference.

Conference Pac Symp Biocomput · 2003 We recently developed an approach for testing the accuracy of network inference algorithms by applying them to biologically realistic simulations with known network topology. Here, we seek to determine the degree to which the network topology and data samp ... Open Access Link to item Cite

Joint classifier and feature optimization for cancer diagnosis using gene expression data

Conference Proceedings of the Annual International Conference on Computational Molecular Biology, RECOMB · January 1, 2003 Recent research has demonstrated quite convincingly that accurate cancer diagnosis can be achieved by constructing classifiers that arc designed to compare the gene expression profile of a tissue of unknown cancer status to a database of stored expression ... Full text Cite

A framework for integrating the songbird brain.

Journal Article J Comp Physiol A Neuroethol Sens Neural Behav Physiol · December 2002 Biological systems by default involve complex components with complex relationships. To decipher how biological systems work, we assume that one needs to integrate information over multiple levels of complexity. The songbird vocal communication system is i ... Full text Open Access Link to item Cite

Bayesian methods for elucidating genetic regulatory networks

Journal Article IEEE Intelligent Systems and Their Applications · March 1, 2002 The ability to observe and measure how cells respond to diverse treatments will profoundly affect the understanding of cell biology, the diagnosis and treatment of disease, and the efficacy of designing and delivering targeted therapeutics. Bayesian networ ... Full text Cite

Evaluating functional network inference using simulations of complex biological systems.

Journal Article Bioinformatics · 2002 MOTIVATION: Although many network inference algorithms have been presented in the bioinformatics literature, no suitable approach has been formulated for evaluating their effectiveness at recovering models of complex biological systems from limited data. T ... Full text Open Access Link to item Cite

Combining location and expression data for principled discovery of genetic regulatory network models.

Conference Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing · January 2002 We develop principled methods for the automatic induction (discovery) of genetic regulatory network models from multiple data sources and data modalities. Models of regulatory networks are represented as Bayesian networks, allowing the models to compactly ... Cite

Bayesian Methods for Elucidating Genetic Regulatory Networks

Journal Article IEEE Intelligent Systems · January 1, 2002 Full text Cite

Maximum likelihood estimation of optimal scaling factors for expression array normalization

Conference Proceedings of SPIE - The International Society for Optical Engineering · January 1, 2001 Data from expression arrays must be comparable before it can be analyzed rigorously on a large scale. Accurate normalization improves the comparability of expression data because it seeks to account for sources of variation obscuring the underlying variati ... Full text Cite

Using graphical models and genomic expression data to statistically validate models of genetic regulatory networks.

Conference Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing · January 2001 We propose a model-driven approach for analyzing genomic expression data that permits genetic regulatory networks to be represented in a biologically interpretable computational form. Our models permit latent variables capturing unobserved factors, describ ... Full text Cite

Automated constraint-based nucleotide sequence selection for DNA computation.

Journal Article Bio Systems · October 1999 We present techniques for automating the design of computational systems built using DNA, given a set of high-level constraints on the desired behavior and performance of the system. We have developed a program called SCAN that exploits a previously implem ... Full text Cite

Simulating biological reactions: A modular approach.

Conference DNA Based Computers · 1999 Cite

Anonymous authentication of membership in dynamic groups

Conference Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) · January 1, 1999 We present a series of protocols for authenticating an individual’s membership in a group without revealing that individual's identity and without restricting how the membership of the group may be changed. In systems using these protocols a single message ... Full text Cite