基于Web的基因组浏览器研究现状

测序技术的发展促使人类基因组测序成本急剧降低,测序速度迅速增加,对这些数据的分析和可视化已成为生命科学领域最重要的课题之一.基因组浏览器技术在基因序列分析,遗传密码解读,复杂疾病研究等方面具有重要意义.本文综述了9种主要的基因组浏览器技术,并从可视化内容、可视化形式、软件系统架构等角度分析了它们的特点.最后,探讨了基因组浏览器发展所面临的挑战.     

DictyMOLD-a Dictyostelium discoideum genome browser database

SUMMARY: With the Dictyostelium Genome Project nearing completion, we initiated the construction of a data repository for all Dictyostelium discoideum genomic data. Up to now this database, called DictyMOLD (Dicty Map Of Linked Data), incorporates the recently completed D.discoideum chromosomes 1 and 2 sequences together with related annotations. To visualise maps, sequences and annotations and to provide access for the scientific community a perl-based browser was developed. AVAILABILITY: The DictyMOLD database is freely accessible via http://genome.imb-jena.de/dictyostelium/ CONTACT: gernot@imb-jena.de.     

GenomeView: a next-generation genome browser

Due to ongoing advances in sequencing technologies, billions of nucleotide sequences are now produced on a daily basis. A major challenge is to visualize these data for further downstream analysis. To this end, we present GenomeView, a stand-alone genome browser specifically designed to visualize and manipulate a multitude of genomics data. GenomeView enables users to dynamically browse high volumes of aligned short-read data, with dynamic navigation and semantic zooming, from the whole genome level to the single nucleotide. At the same time, the tool enables visualization of whole genome alignments of dozens of genomes relative to a reference sequence. GenomeView is unique in its capability to interactively handle huge data sets consisting of tens of aligned genomes, thousands of annotation features and millions of mapped short reads both as viewer and editor. GenomeView is freely available as an open source software package.     

Rice-Map: a new-generation rice genome browser

Background

Because the Japanese native cattle Kuchinoshima-Ushi have been isolated in a small island and their lineage has been intensely protected, it has been assumed to date that numerous and valuable genomic variations are conserved in this cattle breed.

Results

In this study, we evaluated genetic features of this breed, including single nucleotide polymorphism (SNP) information, by whole-genome sequencing using a Genome Analyzer II. A total of 64.2 Gb of sequence was generated, of which 86% of the obtained reads were successfully mapped to the reference sequence (Btau 4.0) with BWA. On an average, 93% of the genome was covered by the reads and the number of mapped reads corresponded to 15.8-fold coverage across the covered region. From these data, we identified 6.3 million SNPs, of which more than 5.5 million (87%) were found to be new. Out of the SNPs annotated in the bovine sequence assembly, 20,432 were found in protein-coding regions containing 11,713 nonsynonymous SNPs in 4,643 genes. Furthermore, phylogenetic analysis using sequence data from 10 genes (more than 10 kbp) showed that Kuchinoshima-Ushi is clearly distinct from European domestic breeds of cattle.

Conclusions

These results provide a framework for further genetic studies in the Kuchinoshima-Ushi population and research on functions of SNP-containing genes, which would aid in understanding the molecular basis underlying phenotypic variation of economically important traits in cattle and in improving intrinsic defects in domestic cattle breeds.     

Genquire: genome annotation browser/editor

We present a software package, Genquire, that allows visualization, querying, hand editing, and de novo markup of complete or partially annotated genomes. The system is written in Perl/Tk and uses, where possible, existing BioPerl data models and methods for representation and manipulation of the sequence and annotation objects. An adaptor API is provided to allow Genquire to display a wide range of databases and flat files, and a plugins API provides an interface to other sequence analysis software. AVAILABILITY: Genquire v3.03 is open-source software. The code is available for download and/or contribution at http://www.bioinformatics.org/Genquire     

Combo: a whole genome comparative browser

SUMMARY: Combo is a comparative genome browser that provides a dynamic view of whole genome alignments along with their associated annotations. Combo provides two different visualization perspectives. The perpendicular (dot plot) view provides a dot plot of genome alignments synchronized with a display of genome annotations along each axis. The parallel view displays two genome annotations horizontally, synchronized through a panel displaying local alignments as trapezoids. Users can zoom to any resolution, from whole chromosomes to individual bases. They can select, highlight and view detailed information from specific alignments and annotations. Combo is an organism agnostic and can import data from a variety of file formats. AVAILABILITY: Combo is integrated as part of the Argo Genome Browser which also provides single-genome browsing and editing capabilities. Argo is written in Java, runs on multiple platforms and is freely available for download at http://www.broad.mit.edu/annotation/argo/.     

ABrowse - a customizable next-generation genome browser framework

Background  

With the rapid growth of genome sequencing projects, genome browser is becoming indispensable, not only as a visualization system but also as an interactive platform to support open data access and collaborative work. Thus a customizable genome browser framework with rich functions and flexible configuration is needed to facilitate various genome research projects.     

Genome Annotation Resource Fields--GARFIELD: a genome browser for Felis catus

Annotation features from the 1.9-fold whole-genome shotgun (WGS) sequences of domestic cat have been organized into an interactive web application, Genome Annotation Resource Fields (GARFIELD) (http://lgd.abcc.ncifcrf.gov) at the Laboratory of Genomic Diversity and Advanced Biomedical Computing Center (ABCC) at The National Cancer Institute (NCI). The GARFIELD browser allows the user to view annotations on a per chromosome basis with unplaced contigs provided on placeholder chromosomes. Various tracks on the browser allow display of annotations. A Genes track on the browser includes 20 285 regions that align to genes annotated in other mammalian genomes: Homo sapiens, Pan troglodytes, Mus musculus, Rattus norvegicus, Bos taurus, and Canis familiaris. Also available are tracks that display the contigs that make up the chromosomes and representations of their GC content and repetitive elements as detected using the RepeatMasker (http://www.repeatmasker.org). Data from the browser can be downloaded in FASTA and GFF format, and users can upload their own data to the display. The Felis catus sequences and their chromosome assignments and additional annotations incorporate data analyzed and produced by a multicenter collaboration between NCI, ABCC, Agencourt Biosciences Corporation, Broad Institute of Harvard and Massachusetts Institute of Technology, National Human Genome Research Institute, National Center for Biotechnology and Information, and Texas A&M.     

The UCSC Genome Browser Database

The University of California Santa Cruz (UCSC) Genome Browser Database is an up to date source for genome sequence data integrated with a large collection of related annotations. The database is optimized to support fast interactive performance with the web-based UCSC Genome Browser, a tool built on top of the database for rapid visualization and querying of the data at many levels. The annotations for a given genome are displayed in the browser as a series of tracks aligned with the genomic sequence. Sequence data and annotations may also be viewed in a text-based tabular format or downloaded as tab-delimited flat files. The Genome Browser Database, browsing tools and downloadable data files can all be found on the UCSC Genome Bioinformatics website (http://genome.ucsc.edu), which also contains links to documentation and related technical information.     

The UCSC Known Genes

The University of California Santa Cruz (UCSC) Known Genes dataset is constructed by a fully automated process, based on protein data from Swiss-Prot/TrEMBL (UniProt) and the associated mRNA data from Genbank. The detailed steps of this process are described. Extensive cross-references from this dataset to other genomic and proteomic data were constructed. For each known gene, a details page is provided containing rich information about the gene, together with extensive links to other relevant genomic, proteomic and pathway data. As of July 2005, the UCSC Known Genes are available for human, mouse and rat genomes. The Known Genes serves as a foundation to support several key programs: the Genome Browser, Proteome Browser, Gene Sorter and Table Browser offered at the UCSC website. All the associated data files and program source code are also available. They can be accessed at http://genome.ucsc.edu. The genomic coverage of UCSC Known Genes, RefSeq, Ensembl Genes, H-Invitational and CCDS is analyzed. Although UCSC Known Genes offers the highest genomic and CDS coverage among major human and mouse gene sets, more detailed analysis suggests all of them could be further improved.     

Genomics made easier: An introductory tutorial to genome datamining

Integrated genome databases – such as the UCSC, Ensembl and NCBI MapViewer databases – and their associated data querying and visualization interfaces (e.g. the genome browsers) have transformed the way that molecular biologists, geneticists and bioinformaticists analyze genomic data. Nevertheless, because of the complexity of these tools, many researchers take advantage of only a fraction of their capabilities. In this tutorial, using examples from medical genetics and alternative splicing, I describe some of the biological questions that can be addressed with these techniques. I also show why doing so typically is more effective than using alternative methods and indicate some of the resources available for learning more about the advanced capabilities of these powerful tools.     

Introgression browser: high‐throughput whole‐genome SNP visualization

Breeding by introgressive hybridization is a pivotal strategy to broaden the genetic basis of crops. Usually, the desired traits are monitored in consecutive crossing generations by marker‐assisted selection, but their analyses fail in chromosome regions where crossover recombinants are rare or not viable. Here, we present the Introgression Browser (iBrowser ), a bioinformatics tool aimed at visualizing introgressions at nucleotide or SNP (Single Nucleotide Polymorphisms) accuracy. The software selects homozygous SNPs from Variant Call Format (VCF) information and filters out heterozygous SNPs, multi‐nucleotide polymorphisms (MNPs) and insertion–deletions (InDels). For data analysis iBrowser makes use of sliding windows, but if needed it can generate any desired fragmentation pattern through General Feature Format (GFF) information. In an example of tomato (Solanum lycopersicum) accessions we visualize SNP patterns and elucidate both position and boundaries of the introgressions. We also show that our tool is capable of identifying alien DNA in a panel of the closely related S. pimpinellifolium by examining phylogenetic relationships of the introgressed segments in tomato. In a third example, we demonstrate the power of the iBrowser in a panel of 597 Arabidopsis accessions, detecting the boundaries of a SNP‐free region around a polymorphic 1.17 Mbp inverted segment on the short arm of chromosome 4. The architecture and functionality of iBrowser makes the software appropriate for a broad set of analyses including SNP mining, genome structure analysis, and pedigree analysis. Its functionality, together with the capability to process large data sets and efficient visualization of sequence variation, makes iBrowser a valuable breeding tool.