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We systematically generated large-scale data sets to improve genome annotation for the nematode Caenorhabditis elegans, a key model organism. These data sets include transcriptome profiling across a developmental time course, genome-wide identification of transcription factor-binding sites, and maps of chromatin organization. From this, we created more(More)
We present a network framework for analyzing multi-level regulation in higher eukaryotes based on systematic integration of various high-throughput datasets. The network, namely the integrated regulatory network, consists of three major types of regulation: TF→gene, TF→miRNA and miRNA→gene. We identified the target genes and target miRNAs for a set of TFs(More)
Transcription factors are key components of regulatory networks that control development, as well as the response to environmental stimuli. We have established an experimental pipeline in Caenorhabditis elegans that permits global identification of the binding sites for transcription factors using chromatin immunoprecipitation and deep sequencing. We(More)
Regulation of gene expression by sequence-specific transcription factors is central to developmental programs and depends on the binding of transcription factors with target sites in the genome. To date, most such analyses in Caenorhabditis elegans have focused on the interactions between a single transcription factor with one or a few select target genes.(More)
In the human genome, it has been estimated that considerably more sequence is under natural selection in non-coding regions [such as transcription-factor binding sites (TF-binding sites) and non-coding RNAs (ncRNAs)] compared to protein-coding ones. However, less attention has been paid to them. To study selective pressure on non-coding elements, we use(More)
The transcriptome is the readout of the genome. Identifying common features in it across distant species can reveal fundamental principles. To this end, the ENCODE and modENCODE consortia have generated large amounts of matched RNA-sequencing data for human, worm and fly. Uniform processing and comprehensive annotation of these data allow comparison across(More)
Small interfering RNA (siRNA) are widely used to infer gene function. Here, insights in the equilibrium of siRNA-target hybridization are used for selection of efficient siRNA. The accessibilities of siRNA and target mRNA for hybridization, as measured by folding free energy change, are shown to be significantly correlated with efficacy. For this study, a(More)
The tumor suppressor Rb/E2F regulates gene expression to control differentiation in multiple tissues during development, although how it directs tissue-specific gene regulation in vivo is poorly understood. We determined the genome-wide binding profiles for Caenorhabditis elegans Rb/E2F-like components in the germline, in the intestine and broadly(More)
Preprint Accepted likely to differ from the final, published version. Peer-reviewed and accepted for publication but not copyedited or typeset; preprint is object identifier (DOIs) and date of initial publication. by PubMed from initial publication. Citations to Advance online articles must include the digital publication). Advance online articles are(More)
A complete set of nearest neighbor parameters to predict the enthalpy change of RNA secondary structure formation was derived. These parameters can be used with available free energy nearest neighbor parameters to extend the secondary structure prediction of RNA sequences to temperatures other than 37 degrees C. The parameters were tested by predicting the(More)