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Uwe Ohler

Adjunct Associate Professor in the Department of Biostatistics & Bioinformatics
Biostatistics & Bioinformatics, Division of Biostatistics
Duke Box 2721, Durham, NC 27710
2424 Erwin Road Ste 1102, Hock Plaza 11069, Durham, NC 27708

Selected Publications


Genome-wide identification of regulatory elements in Sertoli cells.

Journal Article Development · February 15, 2017 A current goal of molecular biology is to identify transcriptional networks that regulate cell differentiation. However, identifying functional gene regulatory elements has been challenging in the context of developing tissues where material is limited and ... Full text Link to item Cite

High-Resolution Expression Map of the Arabidopsis Root Reveals Alternative Splicing and lincRNA Regulation.

Journal Article Dev Cell · November 21, 2016 The extent to which alternative splicing and long intergenic noncoding RNAs (lincRNAs) contribute to the specialized functions of cells within an organ is poorly understood. We generated a comprehensive dataset of gene expression from individual cell types ... Full text Link to item Cite

Super-resolution ribosome profiling reveals unannotated translation events in Arabidopsis.

Journal Article Proc Natl Acad Sci U S A · November 8, 2016 Deep sequencing of ribosome footprints (ribosome profiling) maps and quantifies mRNA translation. Because ribosomes decode mRNA every 3 nt, the periodic property of ribosome footprints could be used to identify novel translated ORFs. However, due to the li ... Full text Link to item Cite

Transcriptional control of tissue formation throughout root development.

Journal Article Science · October 23, 2015 Tissue patterns are dynamically maintained. Continuous formation of plant tissues during postembryonic growth requires asymmetric divisions and the specification of cell lineages. We show that the BIRDs and SCARECROW regulate lineage identity, positional s ... Full text Link to item Cite

Human promoters are intrinsically directional.

Journal Article Mol Cell · February 19, 2015 Divergent transcription, in which reverse-oriented transcripts occur upstream of eukaryotic promoters in regions devoid of annotated genes, has been suggested to be a general property of active promoters. Here we show that the human basal RNA polymerase II ... Full text Link to item Cite

Explicit DNase sequence bias modeling enables high-resolution transcription factor footprint detection.

Journal Article Nucleic Acids Res · October 29, 2014 DNaseI footprinting is an established assay for identifying transcription factor (TF)-DNA interactions with single base pair resolution. High-throughput DNase-seq assays have recently been used to detect in vivo DNase footprints across the genome. Multiple ... Full text Open Access Link to item Cite

Improved transcript isoform discovery using ORF graphs.

Journal Article Bioinformatics · July 15, 2014 MOTIVATION: High-throughput sequencing of RNA in vivo facilitates many applications, not the least of which is the cataloging of variant splice isoforms of protein-coding messenger RNAs. Although many solutions have been proposed for reconstructing putativ ... Full text Link to item Cite

Identification of the RNA recognition element of the RBPMS family of RNA-binding proteins and their transcriptome-wide mRNA targets.

Journal Article RNA · July 2014 Recent studies implicated the RNA-binding protein with multiple splicing (RBPMS) family of proteins in oocyte, retinal ganglion cell, heart, and gastrointestinal smooth muscle development. These RNA-binding proteins contain a single RNA recognition motif ( ... Full text Link to item Cite

COUGER--co-factors associated with uniquely-bound genomic regions.

Journal Article Nucleic Acids Res · July 2014 Most transcription factors (TFs) belong to protein families that share a common DNA binding domain and have very similar DNA binding preferences. However, many paralogous TFs (i.e. members of the same TF family) perform different regulatory functions and i ... Full text Link to item Cite

Paired-end analysis of transcription start sites in Arabidopsis reveals plant-specific promoter signatures.

Journal Article Plant Cell · July 2014 Understanding plant gene promoter architecture has long been a challenge due to the lack of relevant large-scale data sets and analysis methods. Here, we present a publicly available, large-scale transcription start site (TSS) data set in plants using a hi ... Full text Link to item Cite

Integrated detection of natural antisense transcripts using strand-specific RNA sequencing data.

Journal Article Genome Res · October 2013 Pairs of RNA molecules transcribed from partially or entirely complementary loci are called cis-natural antisense transcripts (cis-NATs), and they play key roles in the regulation of gene expression in many organisms. A promising experimental tool for prof ... Full text Link to item Cite

Distinct polyadenylation landscapes of diverse human tissues revealed by a modified PA-seq strategy.

Journal Article BMC Genomics · September 11, 2013 BACKGROUND: Polyadenylation is a key regulatory step in eukaryotic gene expression and one of the major contributors of transcriptome diversity. Aberrant polyadenylation often associates with expression defects and leads to human diseases. RESULTS: To bett ... Full text Link to item Cite

Sustained-input switches for transcription factors and microRNAs are central building blocks of eukaryotic gene circuits.

Journal Article Genome Biol · August 23, 2013 WaRSwap is a randomization algorithm that for the first time provides a practical network motif discovery method for large multi-layer networks, for example those that include transcription factors, microRNAs, and non-regulatory protein coding genes. The a ... Full text Open Access Link to item Cite

MicroRNA target site identification by integrating sequence and binding information.

Journal Article Nat Methods · July 2013 High-throughput sequencing has opened numerous possibilities for the identification of regulatory RNA-binding events. Cross-linking and immunoprecipitation of Argonaute proteins can pinpoint a microRNA (miRNA) target site within tens of bases but leaves th ... Full text Link to item Cite

Genome-wide identification and predictive modeling of tissue-specific alternative polyadenylation.

Journal Article Bioinformatics · July 1, 2013 MOTIVATION: Pre-mRNA cleavage and polyadenylation are essential steps for 3'-end maturation and subsequent stability and degradation of mRNAs. This process is highly controlled by cis-regulatory elements surrounding the cleavage/polyadenylation sites (poly ... Full text Link to item Cite

Automated annotation of gene expression image sequences via non-parametric factor analysis and conditional random fields.

Journal Article Bioinformatics · July 1, 2013 MOTIVATION: Computational approaches for the annotation of phenotypes from image data have shown promising results across many applications, and provide rich and valuable information for studying gene function and interactions. While data are often availab ... Full text Link to item Cite

MicroRNA target site identification by integrating sequence and binding information

Journal Article Nature Methods · May 26, 2013 High-throughput sequencing has opened numerous possibilities for the identification of regulatory RNA-binding events. Cross-linking and immunoprecipitation of Argonaute proteins can pinpoint a microRNA (miRNA) target site within tens of bases but leaves th ... Full text Cite

Fine time course expression analysis identifies cascades of activation and repression and maps a putative regulator of mammalian sex determination.

Journal Article PLoS Genet · 2013 In vertebrates, primary sex determination refers to the decision within a bipotential organ precursor to differentiate as a testis or ovary. Bifurcation of organ fate begins between embryonic day (E) 11.0-E12.0 in mice and likely involves a dynamic transcr ... Full text Link to item Cite

MicroRNA target site identification by integrating sequence and binding information

Journal Article Nature Methods · 2013 High-throughput sequencing has opened numerous possibilities for the identification of regulatory RNA-binding events. Cross-linking and immunoprecipitation of Argonaute proteins can pinpoint a microRNA (miRNA) target site within tens of bases but leaves th ... Full text Cite

Genome-wide identification of regulatory elements in Sertoli cells.

Journal Article Development · February 15, 2017 A current goal of molecular biology is to identify transcriptional networks that regulate cell differentiation. However, identifying functional gene regulatory elements has been challenging in the context of developing tissues where material is limited and ... Full text Link to item Cite

High-Resolution Expression Map of the Arabidopsis Root Reveals Alternative Splicing and lincRNA Regulation.

Journal Article Dev Cell · November 21, 2016 The extent to which alternative splicing and long intergenic noncoding RNAs (lincRNAs) contribute to the specialized functions of cells within an organ is poorly understood. We generated a comprehensive dataset of gene expression from individual cell types ... Full text Link to item Cite

Super-resolution ribosome profiling reveals unannotated translation events in Arabidopsis.

Journal Article Proc Natl Acad Sci U S A · November 8, 2016 Deep sequencing of ribosome footprints (ribosome profiling) maps and quantifies mRNA translation. Because ribosomes decode mRNA every 3 nt, the periodic property of ribosome footprints could be used to identify novel translated ORFs. However, due to the li ... Full text Link to item Cite

Transcriptional control of tissue formation throughout root development.

Journal Article Science · October 23, 2015 Tissue patterns are dynamically maintained. Continuous formation of plant tissues during postembryonic growth requires asymmetric divisions and the specification of cell lineages. We show that the BIRDs and SCARECROW regulate lineage identity, positional s ... Full text Link to item Cite

Human promoters are intrinsically directional.

Journal Article Mol Cell · February 19, 2015 Divergent transcription, in which reverse-oriented transcripts occur upstream of eukaryotic promoters in regions devoid of annotated genes, has been suggested to be a general property of active promoters. Here we show that the human basal RNA polymerase II ... Full text Link to item Cite

Explicit DNase sequence bias modeling enables high-resolution transcription factor footprint detection.

Journal Article Nucleic Acids Res · October 29, 2014 DNaseI footprinting is an established assay for identifying transcription factor (TF)-DNA interactions with single base pair resolution. High-throughput DNase-seq assays have recently been used to detect in vivo DNase footprints across the genome. Multiple ... Full text Open Access Link to item Cite

Improved transcript isoform discovery using ORF graphs.

Journal Article Bioinformatics · July 15, 2014 MOTIVATION: High-throughput sequencing of RNA in vivo facilitates many applications, not the least of which is the cataloging of variant splice isoforms of protein-coding messenger RNAs. Although many solutions have been proposed for reconstructing putativ ... Full text Link to item Cite

Identification of the RNA recognition element of the RBPMS family of RNA-binding proteins and their transcriptome-wide mRNA targets.

Journal Article RNA · July 2014 Recent studies implicated the RNA-binding protein with multiple splicing (RBPMS) family of proteins in oocyte, retinal ganglion cell, heart, and gastrointestinal smooth muscle development. These RNA-binding proteins contain a single RNA recognition motif ( ... Full text Link to item Cite

COUGER--co-factors associated with uniquely-bound genomic regions.

Journal Article Nucleic Acids Res · July 2014 Most transcription factors (TFs) belong to protein families that share a common DNA binding domain and have very similar DNA binding preferences. However, many paralogous TFs (i.e. members of the same TF family) perform different regulatory functions and i ... Full text Link to item Cite

Paired-end analysis of transcription start sites in Arabidopsis reveals plant-specific promoter signatures.

Journal Article Plant Cell · July 2014 Understanding plant gene promoter architecture has long been a challenge due to the lack of relevant large-scale data sets and analysis methods. Here, we present a publicly available, large-scale transcription start site (TSS) data set in plants using a hi ... Full text Link to item Cite

Integrated detection of natural antisense transcripts using strand-specific RNA sequencing data.

Journal Article Genome Res · October 2013 Pairs of RNA molecules transcribed from partially or entirely complementary loci are called cis-natural antisense transcripts (cis-NATs), and they play key roles in the regulation of gene expression in many organisms. A promising experimental tool for prof ... Full text Link to item Cite

Distinct polyadenylation landscapes of diverse human tissues revealed by a modified PA-seq strategy.

Journal Article BMC Genomics · September 11, 2013 BACKGROUND: Polyadenylation is a key regulatory step in eukaryotic gene expression and one of the major contributors of transcriptome diversity. Aberrant polyadenylation often associates with expression defects and leads to human diseases. RESULTS: To bett ... Full text Link to item Cite

Sustained-input switches for transcription factors and microRNAs are central building blocks of eukaryotic gene circuits.

Journal Article Genome Biol · August 23, 2013 WaRSwap is a randomization algorithm that for the first time provides a practical network motif discovery method for large multi-layer networks, for example those that include transcription factors, microRNAs, and non-regulatory protein coding genes. The a ... Full text Open Access Link to item Cite

MicroRNA target site identification by integrating sequence and binding information.

Journal Article Nat Methods · July 2013 High-throughput sequencing has opened numerous possibilities for the identification of regulatory RNA-binding events. Cross-linking and immunoprecipitation of Argonaute proteins can pinpoint a microRNA (miRNA) target site within tens of bases but leaves th ... Full text Link to item Cite

Genome-wide identification and predictive modeling of tissue-specific alternative polyadenylation.

Journal Article Bioinformatics · July 1, 2013 MOTIVATION: Pre-mRNA cleavage and polyadenylation are essential steps for 3'-end maturation and subsequent stability and degradation of mRNAs. This process is highly controlled by cis-regulatory elements surrounding the cleavage/polyadenylation sites (poly ... Full text Link to item Cite

Automated annotation of gene expression image sequences via non-parametric factor analysis and conditional random fields.

Journal Article Bioinformatics · July 1, 2013 MOTIVATION: Computational approaches for the annotation of phenotypes from image data have shown promising results across many applications, and provide rich and valuable information for studying gene function and interactions. While data are often availab ... Full text Link to item Cite

MicroRNA target site identification by integrating sequence and binding information

Journal Article Nature Methods · May 26, 2013 High-throughput sequencing has opened numerous possibilities for the identification of regulatory RNA-binding events. Cross-linking and immunoprecipitation of Argonaute proteins can pinpoint a microRNA (miRNA) target site within tens of bases but leaves th ... Full text Cite

Fine time course expression analysis identifies cascades of activation and repression and maps a putative regulator of mammalian sex determination.

Journal Article PLoS Genet · 2013 In vertebrates, primary sex determination refers to the decision within a bipotential organ precursor to differentiate as a testis or ovary. Bifurcation of organ fate begins between embryonic day (E) 11.0-E12.0 in mice and likely involves a dynamic transcr ... Full text Link to item Cite

MicroRNA target site identification by integrating sequence and binding information

Journal Article Nature Methods · 2013 High-throughput sequencing has opened numerous possibilities for the identification of regulatory RNA-binding events. Cross-linking and immunoprecipitation of Argonaute proteins can pinpoint a microRNA (miRNA) target site within tens of bases but leaves th ... Full text Cite

FMRP targets distinct mRNA sequence elements to regulate protein expression.

Journal Article Nature · December 20, 2012 Fragile X syndrome (FXS) is a multi-organ disease that leads to mental retardation, macro-orchidism in males and premature ovarian insufficiency in female carriers. FXS is also a prominent monogenic disease associated with autism spectrum disorders (ASDs). ... Full text Link to item Cite

A microfluidic device and computational platform for high-throughput live imaging of gene expression.

Journal Article Nat Methods · November 2012 To fully describe gene expression dynamics requires the ability to quantitatively capture expression in individual cells over time. Automated systems for acquiring and analyzing real-time images are needed to obtain unbiased data across many samples and co ... Full text Link to item Cite

Chromatin accessibility reveals insights into androgen receptor activation and transcriptional specificity.

Journal Article Genome Biol · October 3, 2012 BACKGROUND: Epigenetic mechanisms such as chromatin accessibility impact transcription factor binding to DNA and transcriptional specificity. The androgen receptor (AR), a master regulator of the male phenotype and prostate cancer pathogenesis, acts primar ... Full text Link to item Cite

Predicting cell-type-specific gene expression from regions of open chromatin.

Journal Article Genome Res · September 2012 Complex patterns of cell-type-specific gene expression are thought to be achieved by combinatorial binding of transcription factors (TFs) to sequence elements in regulatory regions. Predicting cell-type-specific expression in mammals has been hindered by t ... Full text Link to item Cite

Translocation of sickle cell erythrocyte microRNAs into Plasmodium falciparum inhibits parasite translation and contributes to malaria resistance.

Journal Article Cell Host Microbe · August 16, 2012 Erythrocytes carrying a variant hemoglobin allele (HbS), which causes sickle cell disease and resists infection by the malaria parasite Plasmodium falciparum. The molecular basis of this resistance, which has long been recognized as multifactorial, remains ... Full text Link to item Cite

Genome-wide search for miRNA-target interactions in Arabidopsis thaliana with an integrated approach.

Conference BMC Genomics · June 11, 2012 BACKGROUND: MiRNA are about 22nt long small noncoding RNAs that post transcriptionally regulate gene expression in animals, plants and protozoa. Confident identification of MiRNA-Target Interactions (MTI) is vital to understand their function. Currently, s ... Full text Link to item Cite

The protein expression landscape of the Arabidopsis root.

Journal Article Proc Natl Acad Sci U S A · May 1, 2012 Because proteins are the major functional components of cells, knowledge of their cellular localization is crucial to gaining an understanding of the biology of multicellular organisms. We have generated a protein expression map of the Arabidopsis root pro ... Full text Link to item Cite

High-resolution experimental and computational profiling of tissue-specific known and novel miRNAs in Arabidopsis.

Journal Article Genome Res · January 2012 Small non-coding RNAs (ncRNAs) are key regulators of plant development through modulation of the processing, stability, and translation of larger RNAs. We present small RNA data sets comprising more than 200 million aligned Illumina sequence reads covering ... Full text Link to item Cite

The viral and cellular microRNA targetome in lymphoblastoid cell lines.

Journal Article PLoS Pathog · January 2012 Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus linked to a number of B cell cancers and lymphoproliferative disorders. During latent infection, EBV expresses 25 viral pre-microRNAs (miRNAs) and induces the expression of specific host miRNAs, su ... Full text Link to item Cite

The Drosophila Translational Control Element (TCE) is required for high-level transcription of many genes that are specifically expressed in testes.

Journal Article PLoS One · 2012 To investigate the importance of core promoter elements for tissue-specific transcription of RNA polymerase II genes, we examined testis-specific transcription in Drosophila melanogaster. Bioinformatic analyses of core promoter sequences from 190 genes tha ... Full text Link to item Cite

imiRTP: An integrated method to identifying miRNA-target interactions in Arabidopsis thaliana

Journal Article Proceedings - 2011 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2011 · December 1, 2011 MiRNA are about 22nt long small noncoding RNAs that post transcription ally regulate gene expression in animals, plants and protozoa. Confident identification of MiRNA-Target Interactions (MTI) is vital to understand their function. Currently, several inte ... Full text Cite

Viral microRNA targetome of KSHV-infected primary effusion lymphoma cell lines.

Journal Article Cell Host Microbe · November 17, 2011 Primary effusion lymphoma (PEL) is caused by Kaposi's sarcoma-associated herpesvirus (KSHV) and frequently also harbors Epstein-Barr virus (EBV). The expression of KSHV- and EBV-encoded microRNAs (miRNAs) in PELs suggests a role for these miRNAs in latency ... Full text Link to item Cite

PARalyzer: definition of RNA binding sites from PAR-CLIP short-read sequence data.

Journal Article Genome Biol · August 18, 2011 Crosslinking and immunoprecipitation (CLIP) protocols have made it possible to identify transcriptome-wide RNA-protein interaction sites. In particular, PAR-CLIP utilizes a photoactivatable nucleoside for more efficient crosslinking. We present an approach ... Full text Link to item Cite

Integrative regulatory mapping indicates that the RNA-binding protein HuR couples pre-mRNA processing and mRNA stability.

Journal Article Mol Cell · August 5, 2011 RNA-binding proteins coordinate the fates of multiple RNAs, but the principles underlying these global interactions remain poorly understood. We elucidated regulatory mechanisms of the RNA-binding protein HuR, by integrating data from diverse high-throughp ... Full text Open Access Link to item Cite

Automatic annotation of spatial expression patterns via sparse Bayesian factor models.

Journal Article PLoS Comput Biol · July 2011 Advances in reporters for gene expression have made it possible to document and quantify expression patterns in 2D-4D. In contrast to microarrays, which provide data for many genes but averaged and/or at low resolution, images reveal the high spatial dynam ... Full text Open Access Link to item Cite

A stele-enriched gene regulatory network in the Arabidopsis root.

Journal Article Mol Syst Biol · January 18, 2011 Tightly controlled gene expression is a hallmark of multicellular development and is accomplished by transcription factors (TFs) and microRNAs (miRNAs). Although many studies have focused on identifying downstream targets of these molecules, less is known ... Full text Link to item Cite

Transcription initiation patterns indicate divergent strategies for gene regulation at the chromatin level.

Journal Article PLoS Genet · January 13, 2011 The application of deep sequencing to map 5' capped transcripts has confirmed the existence of at least two distinct promoter classes in metazoans: "focused" promoters with transcription start sites (TSSs) that occur in a narrowly defined genomic span and ... Full text Link to item Cite

Assessing the utility of thermodynamic features for microRNA target prediction under relaxed seed and no conservation requirements.

Journal Article PLoS One · 2011 BACKGROUND: Many computational microRNA target prediction tools are focused on several key features, including complementarity to 5'seed of miRNAs and evolutionary conservation. While these features allow for successful target identification, not all miRNA ... Full text Open Access Link to item Cite

Modeling the evolution of regulatory elements by simultaneous detection and alignment with phylogenetic pair HMMs.

Journal Article PLoS Comput Biol · December 16, 2010 The computational detection of regulatory elements in DNA is a difficult but important problem impacting our progress in understanding the complex nature of eukaryotic gene regulation. Attempts to utilize cross-species conservation for this task have been ... Full text Open Access Link to item Cite

Gene expression divergence recapitulates the developmental hourglass model.

Journal Article Nature · December 9, 2010 The observation that animal morphology tends to be conserved during the embryonic phylotypic period (a period of maximal similarity between the species within each animal phylum) led to the proposition that embryogenesis diverges more extensively early and ... Full text Link to item Cite

The TCT motif, a key component of an RNA polymerase II transcription system for the translational machinery.

Journal Article Genes Dev · September 15, 2010 The TCT motif (polypyrimidine initiator) encompasses the transcription start site of nearly all ribosomal protein genes in Drosophila and mammals. The TCT motif is required for transcription of ribosomal protein gene promoters. The TCT element resembles th ... Full text Link to item Cite

An alignment-free method to identify candidate orthologous enhancers in multiple Drosophila genomes.

Journal Article Bioinformatics · September 1, 2010 MOTIVATION: Evolutionarily conserved non-coding genomic sequences represent a potentially rich source for the discovery of gene regulatory region such as transcriptional enhancers. However, detecting orthologous enhancers using alignment-based methods in h ... Full text Link to item Cite

A paired-end sequencing strategy to map the complex landscape of transcription initiation.

Journal Article Nat Methods · July 2010 Recent studies using high-throughput sequencing protocols have uncovered the complexity of mammalian transcription by RNA polymerase II, helping to define several initiation patterns in which transcription start sites (TSSs) cluster in both narrow and broa ... Full text Open Access Link to item Cite

Extraction and comparison of gene expression patterns from 2D RNA in situ hybridization images.

Journal Article Bioinformatics · March 15, 2010 MOTIVATION: Recent advancements in high-throughput imaging have created new large datasets with tens of thousands of gene expression images. Methods for capturing these spatial and/or temporal expression patterns include in situ hybridization or fluorescen ... Full text Link to item Cite

Evidence-ranked motif identification.

Journal Article Genome Biol · 2010 cERMIT is a computationally efficient motif discovery tool based on analyzing genome-wide quantitative regulatory evidence. Instead of pre-selecting promising candidate sequences, it utilizes information across all sequence regions to search for high-scori ... Full text Open Access Link to item Cite

Mapping the complexity of transcription control in higher eukaryotes.

Journal Article Genome Biol · 2010 Recent genomic analyses suggest the importance of combinatorial regulation by broadly expressed transcription factors rather than expression domains characterized by highly specific factors. ... Full text Open Access Link to item Cite

Promoting developmental transcription.

Journal Article Development · January 2010 Animal growth and development depend on the precise control of gene expression at the level of transcription. A central role in the regulation of developmental transcription is attributed to transcription factors that bind DNA enhancer elements, which are ... Full text Open Access Link to item Cite

Measuring spatial preferences at fine-scale resolution identifies known and novel cis-regulatory element candidates and functional motif-pair relationships.

Journal Article Nucleic Acids Res · July 2009 Transcriptional regulation is mediated by the collective binding of proteins called transcription factors to cis-regulatory elements. A handful of factors are known to function at particular distances from the transcription start site, although the extent ... Full text Link to item Cite

A transcription factor affinity-based code for mammalian transcription initiation.

Journal Article Genome Res · April 2009 Featured Publication The recent arrival of large-scale cap analysis of gene expression (CAGE) data sets in mammals provides a wealth of quantitative information on coding and noncoding RNA polymerase II transcription start sites (TSS). Genome-wide CAGE studies reveal that a la ... Full text Link to item Cite

Complexity reduction in context-dependent DNA substitution models.

Journal Article Bioinformatics · January 15, 2009 MOTIVATION: The modeling of conservation patterns in genomic DNA has become increasingly popular for a number of bioinformatic applications. While several systems developed to date incorporate context-dependence in their substitution models, the impact on ... Full text Link to item Cite

Motif composition, conservation and condition-specificity of single and alternative transcription start sites in the Drosophila genome.

Journal Article Genome Biol · 2009 Featured Publication BACKGROUND: Transcription initiation is a key component in the regulation of gene expression. mRNA 5' full-length sequencing techniques have enhanced our understanding of mammalian transcription start sites (TSSs), revealing different initiation patterns o ... Full text Link to item Cite

A viral microRNA functions as an orthologue of cellular miR-155.

Journal Article Nature · December 13, 2007 Featured Publication All metazoan eukaryotes express microRNAs (miRNAs), roughly 22-nucleotide regulatory RNAs that can repress the expression of messenger RNAs bearing complementary sequences. Several DNA viruses also express miRNAs in infected cells, suggesting a role in vir ... Full text Link to item Cite

Gene prediction methods

Chapter · December 1, 2007 Most computational gene-finding methods in current use are derived from the fields of natural language processing and speech recognition. These latter fields are concerned with parsing spoken or written language into functional components such as nouns, ve ... Full text Cite

Predicting non-coding RNA transcripts

Chapter · December 1, 2007 Non-coding RNAs are defined as all functional RNA transcripts other than protein encoding messenger RNAs (mRNA). Thus, they are defined more by what they are not than by what they actually are (Fig. 4.1). This unusual way of defining ncRNAs reflects a hist ... Full text Cite

Advancing the state of the art in computational gene prediction

Journal Article Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) · December 1, 2007 Current methods for computationally predicting the locations and intron-exon structures of protein-coding genes in eukaryotic DNA are largely based on probabilistic, state-based generative models such as hidden Markov models and their various extensions. U ... Cite

A high-resolution root spatiotemporal map reveals dominant expression patterns.

Journal Article Science · November 2, 2007 Featured Publication Transcriptional programs that regulate development are exquisitely controlled in space and time. Elucidating these programs that underlie development is essential to understanding the acquisition of cell and tissue identity. We present microarray expressio ... Full text Link to item Cite

Spatial preferences of microRNA targets in 3' untranslated regions.

Journal Article BMC Genomics · June 7, 2007 Featured Publication BACKGROUND: MicroRNAs are an important class of regulatory RNAs which repress animal genes by preferentially interacting with complementary sequence motifs in the 3' untranslated region (UTR) of target mRNAs. Computational methods have been developed which ... Full text Link to item Cite

Detection of broadly expressed neuronal genes in C. elegans.

Journal Article Dev Biol · February 15, 2007 The genes that are expressed in most or all types of neurons define generic neuronal features and provide a window into the developmental origin and function of the nervous system. Few such genes (sometimes referred to as pan-neuronal or broadly expressed ... Full text Link to item Cite

Phylogenetic simulation of promoter evolution: estimation and modeling of binding site turnover events and assessment of their impact on alignment tools.

Journal Article Genome Biol · 2007 BACKGROUND: The phenomenon of functional site turnover has important implications for the study of regulatory region evolution, such as for promoter sequence alignments and transcription factor binding site (TFBS) identification. At present, it remains dif ... Full text Link to item Cite

Quantification of transcription factor expression from Arabidopsis images.

Journal Article Bioinformatics · July 15, 2006 Featured Publication MOTIVATION: Confocal microscopy has long provided qualitative information for a variety of applications in molecular biology. Recent advances have led to extensive image datasets, which can now serve as new data sources to obtain quantitative gene expressi ... Full text Link to item Cite

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

Journal Article Bioinformatics · July 15, 2006 Featured Publication 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

Optimized mixed Markov models for motif identification.

Journal Article BMC Bioinformatics · June 2, 2006 BACKGROUND: Identifying functional elements, such as transcriptional factor binding sites, is a fundamental step in reconstructing gene regulatory networks and remains a challenging issue, largely due to limited availability of training samples. RESULTS: W ... Full text Link to item Cite

Transcriptional and posttranscriptional regulation of transcription factor expression in Arabidopsis roots.

Journal Article Proc Natl Acad Sci U S A · April 11, 2006 Featured Publication Understanding how the expression of transcription factor (TF) genes is modulated is essential for reconstructing gene regulatory networks. There is increasing evidence that sequences other than upstream noncoding can contribute to modulating gene expressio ... Full text Link to item Cite

Identification of core promoter modules in Drosophila and their application in accurate transcription start site prediction.

Journal Article Nucleic Acids Res · 2006 The reliable recognition of eukaryotic RNA polymerase II core promoters, and the associated transcription start sites (TSSs) of genes, has been an ongoing challenge for computational biology. High throughput experimental methods such as tiling arrays or 5' ... Full text Link to item Cite

Performance assessment of promoter predictions on ENCODE regions in the EGASP experiment.

Journal Article Genome biology · January 2006 BackgroundThis study analyzes the predictions of a number of promoter predictors on the ENCODE regions of the human genome as part of the ENCODE Genome Annotation Assessment Project (EGASP). The systems analyzed operate on various principles and w ... Full text Cite

Recognition of unknown conserved alternatively spliced exons.

Journal Article PLoS Comput Biol · July 2005 Featured Publication The split structure of most mammalian protein-coding genes allows for the potential to produce multiple different mRNA and protein isoforms from a single gene locus through the process of alternative splicing (AS). We propose a computational approach calle ... Full text Link to item Cite

Patterns of flanking sequence conservation and a characteristic upstream motif for microRNA gene identification.

Journal Article RNA · September 2004 Featured Publication MicroRNAs are approximately 22-nucleotide (nt) RNAs processed from foldback segments of endogenous transcripts. Some are known to play important gene regulatory roles during animal and plant development by pairing to the messages of protein-coding genes to ... Full text Link to item Cite

The MTE, a new core promoter element for transcription by RNA polymerase II.

Journal Article Genes Dev · July 1, 2004 The core promoter is the ultimate target of the vast network of regulatory factors that contribute to the initiation of transcription by RNA polymerase II. Here we describe the MTE (motif ten element), a new core promoter element that appears to be conserv ... Full text Link to item Cite

Computational analysis of core promoters in the Drosophila genome.

Journal Article Genome Biol · 2002 Featured Publication BACKGROUND: The core promoter, a region of about 100 base-pairs flanking the transcription start site (TSS), serves as the recognition site for the basal transcription apparatus. Drosophila TSSs have generally been mapped by individual experiments; the low ... Full text Link to item Cite

Identification and analysis of eukaryotic promoters: recent computational approaches.

Journal Article Trends Genet · February 2001 Featured Publication The DNA sequence of several higher eukaryotes is now complete, and we know the expression patterns of thousands of genes under a variety of conditions. This gives us the opportunity to identify and analyze the parts of a genome believed to be responsible f ... Full text Link to item Cite

Joint modeling of DNA sequence and physical properties to improve eukaryotic promoter recognition.

Journal Article Bioinformatics · 2001 We present an approach to integrate physical properties of DNA, such as DNA bendability or GC content, into our probabilistic promoter recognition system McPROMOTER. In the new model, a promoter is represented as a sequence of consecutive segments represen ... Full text Link to item Cite

Promoter prediction on a genomic scale--the Adh experience.

Journal Article Genome Res · April 2000 We describe our statistical system for promoter recognition in genomic DNA with which we took part in the Genome Annotation Assessment Project (GASP1). We applied two versions of the system: the first uses a region-based approach toward transcription start ... Full text Link to item Cite

Genome annotation assessment in Drosophila melanogaster.

Journal Article Genome Res · April 2000 Featured Publication Computational methods for automated genome annotation are critical to our community's ability to make full use of the large volume of genomic sequence being generated and released. To explore the accuracy of these automated feature prediction tools in the ... Full text Link to item Cite

Stochastic segment models of eukaryotic promoter regions.

Journal Article Pac Symp Biocomput · 2000 We present a new statistical approach for eukaryotic polymerase II promoter recognition. We apply stochastic segment models in which each state represents a functional part of the promoter. The segments are trained in an unsupervised way. We compare segmen ... Full text Link to item Cite

Interpolated markov chains for eukaryotic promoter recognition.

Journal Article Bioinformatics · May 1999 MOTIVATION: We describe a new content-based approach for the detection of promoter regions of eukaryotic protein encoding genes. Our system is based on three interpolated Markov chains (IMCs) of different order which are trained on coding, non-coding and p ... Full text Link to item Cite