-
Gerstein, M, White, KP, consortium, modERN, Celnicker, S, Reinke, V, Waterston, RH
[
International Worm Meeting,
2015]
Studies of the nematode worm Caenorhabditis elegans and the fruit fly Drosophila melanogaster have vastly increased our understanding of metazoan biology. Both organisms have provided test beds for genome sequencing strategies, and since the publication of their genome sequences at the turn of the century, efforts at understanding the information content of these key genomes have been at the forefront. As members of modENCODE, we established ChIP-seq pipelines and identified binding sites for about 100 transcription factors or chromatin modifiers in each organism. We have now combined efforts and work together as the modERN (model organism encyclopedia of regulatory networks) consortium. We have created a merged, more efficient pipeline to systematically and comprehensively identify binding sites for the remaining ~600 transcription factors (TFs) in each organism. Since the project began in Sept 2013, we have analyzed about 100 additional factors for each organism. We are also embarked on efforts to assign TF binding sites to regulated genes using RNA-seq to monitor gene expression changes in TF loss-of-function animals. We will map these results to a network framework to provide functional validation. In addition, we will perform targeted bioinformatic analyses to examine the association of binding sites between factors, their distribution in the genome, and how they are linked with changes in gene expression from the RNAi experiments. All strains are being deposited in the stock centers. All data are being incorporated in the ENCODE database (www.encodeproject.org) and will be made available through WormBase and FlyBase.
-
[
Genetics,
2019]
Model organisms are essential experimental platforms for discovering gene functions, defining protein and genetic networks, uncovering functional consequences of human genome variation, and for modeling human disease. For decades, researchers who use model organisms have relied on Model Organism Databases (MODs) and the Gene Ontology Consortium (GOC) for expertly curated annotations, and for access to integrated genomic and biological information obtained from the scientific literature and public data archives. Through the development and enforcement of data and semantic standards, these genome resources provide rapid access to the collected knowledge of model organisms in human readable and computation-ready formats that would otherwise require countless hours for individual researchers to assemble on their own. Since their inception, the MODs for the predominant biomedical model organisms [<i>Mus sp</i> (laboratory mouse), <i>Saccharomyces cerevisiae</i>, <i>Drosophila melanogaster</i>, <i>Caenorhabditis elegans</i>, <i>Danio rerio</i>, and <i>Rattus norvegicus</i>] along with the GOC have operated as a network of independent, highly collaborative genome resources. In 2016, these six MODs and the GOC joined forces as the Alliance of Genome Resources (the Alliance). By implementing shared programmatic access methods and data-specific web pages with a unified "look and feel," the Alliance is tackling barriers that have limited the ability of researchers to easily compare common data types and annotations across model organisms. To adapt to the rapidly changing landscape for evaluating and funding core data resources, the Alliance is building a modern, extensible, and operationally efficient "knowledge commons" for model organisms using shared, modular infrastructure.
-
[
Nature,
2002]
A humble nematode has wormed its way into the affection of the scientific community and helped to secure this year's Nobel Prize in Physiology or Medicine. The award goes to three biologists whose work on the model organism Caenorhabditis elegans has yielded insights and spin-offs in such diverse fields as cancer research and modern
-
[
Nature,
1977]
Participants in two days of talks held at the Accademia Lincei in Rome-the oldest scientific foundatin in the modern world, tried to tackle the ancient problem of how eggs plus genes produce animals. It was symptomatic of the renewed interest in Drosophila that the whole of the first day was devoted to that fly...
-
[
Annu Rev Genomics Hum Genet,
2015]
The modENCODE (Model Organism Encyclopedia of DNA Elements) Consortium aimed to map functional elements-including transcripts, chromatin marks, regulatory factor binding sites, and origins of DNA replication-in the model organisms Drosophila melanogaster and Caenorhabditis elegans. During its five-year span, the consortium conducted more than 2,000 genome-wide assays in developmentally staged animals, dissected tissues, and homogeneous cell lines. Analysis of these data sets provided foundational insights into genome, epigenome, and transcriptome structure and the evolutionary turnover of regulatory pathways. These studies facilitated a comparative analysis with similar data types produced by the ENCODE Consortium for human cells. Genome organization differs drastically in these distant species, and yet quantitative relationships among chromatin state, transcription, and cotranscriptional RNA processing are deeply conserved. Of the many biological discoveries of the modENCODE Consortium, we highlight insights that emerged from integrative studies. We focus on operational and scientific lessons that may aid future projects of similar scale or aims in other, emerging model systems.
-
[
Worm Breeder's Gazette,
1994]
The C. elegans genome sequencing project: A progress report. The C. elegans Genome Consortium, Genome Sequencing Center, Washington University School of Medicine, St. Louis, Missouri, USA and Sanger Centre, Hinxton Hall, Cambridge, UK.
-
[
Worm Breeder's Gazette,
1994]
The C. elegans genome sequencing project: A progress report. The C. elegans Genome Consortium, Genome Sequencing Center, Washington University School of Medicine, St. Louis, Missouri, USA and Sanger Centre, Hinxton Hall, Cambridge, UK.
-
[
Phys Rev E Stat Nonlin Soft Matter Phys,
2007]
The rapid accumulation of knowledge and the recent emergence of new dynamic and practically unmoderated information repositories have rendered the classical concept of the hierarchal knowledge structure irrelevant and impossible to impose manually. This led to modern methods of data location, such as browsing or searching, which conceal the underlying information structure. We here propose methods designed to automatically construct a hierarchy from a network of related terms. We apply these methods to Wikipedia and compare the hierarchy obtained from the article network to the complementary acyclic category layer of the Wikipedia and show an excellent fit. We verify our methods in two networks with no a priori hierarchy (the E. Coli genetic regulatory network and the C. Elegans neural network) and a network of function libraries of modern computer operating systems that are intrinsically hierarchical and reproduce a known functional order.
-
[
Bioinformation,
2006]
Computational gene prediction and identifying alternatively spliced isoforms have always been a challenging task. In this paper, we describe the performance of three gene/exon finding programmes namely Fex, Gen view2 and Gene builder capable of predicting open reading frames or exons for a given set of sequences from C. elegans genome. The predicted exons were compared with the 'sequencing consortium' identified exons and degree of consensus among them is discussed. We found that exon prediction by Fex was similar to the consortium prediction as compared to Gen view2 and Gene builder results. Interestingly, some exons (six exons in five genes) predicted positive only by Fex and not by the 'sequencing consortium' are found at the C. elegans EST database. This data is critical for further debate and discussion on gene finding in C. elegans.
-
[
International Worm Meeting,
2007]
The C. elegans Gene Knockout Consortium
(http://www.celeganskoconsortium.omrf.org/) pursues systematic targeted gene disruption in the nematode, both upon request from the research community and in the larger context of the whole set of genes for which human orthologs exist (more than 7,000 genes). We are also now working on nematode specific genes. Previously our work was solely based on a reverse-genetics PCR method to generate single-gene deletions. More recently we have incorporated array Comparative Genome Hybridization (array-CGH) for efficient generation of deletion mutations (see abstract by Maydan et al). The combined strategies of directed and non-directed approaches are improving our throughput and broadening the types of mutations we can identify. All deletions isolated by the consortium are stabilized as homozygous or balanced heterozygous strains, deletion breakpoints are sequenced, and the strains and data are placed immediately into the public domain through our collaborators at the Caenorhabditis Genetics Center and WormBase. Distribution of Consortium strains accounts for a significant proportion of distributions from the CGC and has stood at 20% for the past two calendar years. To date the Consortium has generated deletions in more than 2,300 genes, and most of these have been stabilized and archived at the CGC. In addition, using CGH methodology we have identified over 700 genes missing in either the Hawaiian or Madeiran strains and consequently these genes will not be targeted for deletion by the consortium. Obtaining deletions in all genes in this nematode is the goal of the consortium and the general worm community. The combined efforts of the consortium, the Mitani lab and individuals within the worm community are moving us closer to this goal - analysis of 7205 mutations yields a very conservative estimate of about 5,000 genes with associated deletions. To put this in perspective the nematode community has now matched the yeast community whole genome effort of 5,500 KO''s.