Journal ArticleNature 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 ...
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Journal ArticleGenome Res · December 27, 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 ...
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Journal ArticleGenome 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 ...
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Journal ArticleGenes (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 ...
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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 ...
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Journal ArticleNucleic 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 ...
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Journal ArticleGenome 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 ...
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Journal ArticleGenome 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 ...
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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 ...
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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 ...
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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 ...
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ConferenceRes 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 ...
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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 ...
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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 ...
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Journal ArticleGenome 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 ...
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Journal ArticleGenome 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 ...
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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 ...
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Journal ArticleJ 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 ...
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ConferenceLecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) · January 1, 2017Cite
Journal ArticleDev 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 ...
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Journal ArticleGenome 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 ...
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Journal ArticleGenome 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 ...
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Journal ArticleGenes 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 ...
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Journal ArticleScience · 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 ...
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Journal ArticleScience · 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 ...
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Journal ArticleBioinformatics · 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 ...
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Journal ArticleGenome 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 ...
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Journal ArticleBioinformatics · 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 ...
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Journal ArticleNat 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 ...
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Journal ArticleProceedings 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 ...
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Journal ArticlePacific 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 ...
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ConferenceProceedings - 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 ...
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Journal ArticleGenome 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 ...
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Journal ArticlePacific 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) ...
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Journal ArticleBioinformatics (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 ...
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Journal ArticleRNA · 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 ...
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Journal ArticleJournal 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, ...
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Journal ArticleNucleic 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 ...
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Journal ArticleGenome 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 ...
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Journal ArticleNucleic 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 ...
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Journal ArticleGenome 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 ...
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Journal ArticleGenome 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 ...
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Journal ArticleBioinformatics (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 ...
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Journal ArticleThe 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 ...
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Journal ArticleAdvances 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 ...
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Journal ArticleNature · 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 ...
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ConferencePac 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 ...
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Journal ArticleGenome 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 ...
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Journal ArticlePLoS 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 ...
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Journal ArticleCell 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 ...
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Journal ArticlePLoS 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 ...
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Journal ArticleBioinformatics · 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 ...
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ConferencePac 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 ...
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Journal ArticleBioinformatics (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 ...
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Journal ArticleIEEE 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 ...
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Journal ArticleGenome 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 ...
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Journal ArticleBioinformatics (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 ...
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ConferencePacific 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 ...
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ConferenceAdvances 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 ...
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Journal ArticleBioinformatics · 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 ...
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Journal ArticleIEEE 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 ...
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Journal ArticleJournal 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 ...
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ConferenceConference 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 ...
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ConferencePac 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 ...
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ConferenceProceedings 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 ...
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Journal ArticleJ 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 ...
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Journal ArticleIEEE 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 ...
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Journal ArticleBioinformatics · 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 ...
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ConferencePacific 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 ...
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ConferenceProceedings 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 ...
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ConferencePacific 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 ...
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Journal ArticleBio 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 ...
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ConferenceLecture 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 ...
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