FlyMine is a data warehouse that addresses one of the important challenges of modern biology: how to integrate and make use of the diversity and volume of current biological data. Its main focus is genomic and proteomics data for Drosophila and other insects. It provides web access to integrated data at a number of different levels, from simple browsing to construction of complex queries, which can be executed on either single items or lists. RationaleWith the completion of increasing numbers of genome sequences has come an explosion in the development of both computational and experimental techniques for deciphering the functions of genes, molecules and their interactions. These include theoretical methods for deducing function, such as analysis of protein homologies, structural domain predictions, phylogenetic profiling and analysis of protein domain fusions, as well as experimental techniques, such as microarray-based gene expression and transcription factor binding studies, two-hybrid protein-protein interaction screens, and large-scale RNA interference (RNAi) screens. The result is a huge amount of information and a current challenge is to extract meaningful knowledge and patterns of biological significance that can lead to new experimentally testable hypotheses. Many of these broad datasets, however, are noisy and the data quality can vary significantly. While in some circumstances the data from each of these techniques are useful in their own right, the ability to combine data from different sources facilitates interpretation and potentially allows stronger inferences to be made. Currently, biological data are stored in a wide variety of formats in numerous different places, making their combined analysis difficult: when information from several different databases is required, the assembly of data into a format suitable for querying is a challenge in itself. Sophisticated analysis of diverse data requires that they are available in a form that allows questions to be asked across them and that tools for constructing the questions are available. The development of systems for the integration and combined analysis of diverse data remains a priority in bioinformatics. Avoiding the need to understand and reformat many different data sources is a major benefit for end users of a centralized data access system.A number of studies have illustrated the power of integrating data for cross-validation, functional annotation and generating testable hypotheses (reviewed in [1,2]). These studies have covered a range of data types; some looking at the overlap between two different data sets, for example, protein interaction and expression data [3][4][5][6] Another key component is the use of ontologies that provide a standardized system for naming biological entities and their relationships and this aspect is based on the approach taken by the Chado schema [28]. For example, a large part of the FlyMine data model is based on the Sequence Ontology (a controlled-vocabulary for describing biological sequences) [29...
CRISPR-Cas9 represents a promising technology for genome editing, yet means of safe and efficient delivery remain to be fully realized. Here, we report a novel delivery vehicle to deliver the Cas9 protein and single-guide RNA simultaneously based on DNA nanoclews, yarn-like DNA nanoparticles synthesized by rolling circle amplification. The bio-inspired vehicles efficiently loaded Cas9/single-guide RNA complexes and delivered the complexes to the nuclei of human cells, allowing targeted gene disruptions while maintaining cell viability. Editing was most efficient when the DNA nanoclew sequence and the sgRNA guide sequence were partially complementary, offering a design rule for enhancing delivery. Overall, this strategy provides a versatile platform that could be adapted for delivering other DNA-binding proteins or for functional nucleic acids.
CRISPR-Cas9 represents ap romising platform for genome editing, yet means for its safe and efficient delivery remain to be fully realized. Anovel vehicle that simultaneously delivers the Cas9 protein and single guide RNA( sgRNA) is based on DNAn anoclews,y arn-like DNAn anoparticles that are synthesized by rolling circle amplification. The biologically inspired vehicles were efficiently loaded with Cas9/sgRNA complexes and delivered the complexes to the nuclei of human cells,thus enabling targeted gene disruption while maintaining cell viability.E diting was most efficient when the DNA nanoclew sequence and the sgRNAg uide sequence were partially complementary,o ffering ad esign rule for enhancing delivery.Overall, this strategy provides aversatile method that could be adapted for delivering other DNA-binding proteins or functional nucleic acids.
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