Genomes as geography: using GIS technology to build interactive genome feature maps

Background  

Many commonly used genome browsers display sequence annotations and related attributes as horizontal data tracks that can be toggled on and off according to user preferences. Most genome browsers use only simple keyword searches and limit the display of detailed annotations to one chromosomal region of the genome at a time. We have employed concepts, methodologies, and tools that were developed for the display of geographic data to develop a Genome Spatial Information System (GenoSIS) for displaying genomes spatially, and interacting with genome annotations and related attribute data. In contrast to the paradigm of horizontally stacked data tracks used by most genome browsers, GenoSIS uses the concept of registered spatial layers composed of spatial objects for integrated display of diverse data. In addition to basic keyword searches, GenoSIS supports complex queries, including spatial queries, and dynamically generates genome maps. Our adaptation of the geographic information system (GIS) model in a genome context supports spatial representation of genome features at multiple scales with a versatile and expressive query capability beyond that supported by existing genome browsers.     

Visualizing the genome: techniques for presenting human genome data and annotations

Background  

In order to take full advantage of the newly available public human genome sequence data and associated annotations, biologists require visualization tools ("genome browsers") that can accommodate the high frequency of alternative splicing in human genes and other complexities.     

The Distributed Annotation System

Background  

Currently, most genome annotation is curated by centralized groups with limited resources. Efforts to share annotations transparently among multiple groups have not yet been satisfactory.     

Cinteny: flexible analysis and visualization of synteny and genome rearrangements in multiple organisms

Background  

Identifying syntenic regions, i.e., blocks of genes or other markers with evolutionary conserved order, and quantifying evolutionary relatedness between genomes in terms of chromosomal rearrangements is one of the central goals in comparative genomics. However, the analysis of synteny and the resulting assessment of genome rearrangements are sensitive to the choice of a number of arbitrary parameters that affect the detection of synteny blocks. In particular, the choice of a set of markers and the effect of different aggregation strategies, which enable coarse graining of synteny blocks and exclusion of micro-rearrangements, need to be assessed. Therefore, existing tools and resources that facilitate identification, visualization and analysis of synteny need to be further improved to provide a flexible platform for such analysis, especially in the context of multiple genomes.     

eQTL Viewer: visualizing how sequence variation affects genome-wide transcription

Background  

Expression Quantitative Trait Locus (eQTL) mapping methods have been used to identify the genetic basis of gene expression variations. To map eQTL, thousands of expression profiles are related with sequence polymorphisms across the genome through their correlated variations. These eQTL distribute in many chromosomal regions, each of which can include many genes. The large number of mapping results produced makes it difficult to consider simultaneously the relationships between multiple genomic regions and multiple expressional profiles. There is a need for informative bioinformatics tools to assist the visualization and interpretation of these mapping results.     

ZCURVE_V: a new self-training system for recognizing protein-coding genes in viral and phage genomes

Background  

It necessary to use highly accurate and statistics-based systems for viral and phage genome annotations. The GeneMark systems for gene-finding in virus and phage genomes suffer from some basic drawbacks. This paper puts forward an alternative approach for viral and phage gene-finding to improve the quality of annotations, particularly for newly sequenced genomes.     

Browsing repeats in genomes: Pygram and an application to non-coding region analysis

Background  

A large number of studies on genome sequences have revealed the major role played by repeated sequences in the structure, function, dynamics and evolution of genomes. In-depth repeat analysis requires specialized methods, including visualization techniques, to achieve optimum exploratory power.     

Accessing the SEED Genome Databases via Web Services API: Tools for Programmers

Background  

The SEED integrates many publicly available genome sequences into a single resource. The database contains accurate and up-to-date annotations based on the subsystems concept that leverages clustering between genomes and other clues to accurately and efficiently annotate microbial genomes. The backend is used as the foundation for many genome annotation tools, such as the Rapid Annotation using Subsystems Technology (RAST) server for whole genome annotation, the metagenomics RAST server for random community genome annotations, and the annotation clearinghouse for exchanging annotations from different resources. In addition to a web user interface, the SEED also provides Web services based API for programmatic access to the data in the SEED, allowing the development of third-party tools and mash-ups.     

Two novel missense mutations in the myelin protein zero gene causes Charcot-Marie-Tooth type 2 and Déjérine-Sottas syndrome

Background

Gene-list annotations are critical for researchers to explore the complex relationships between genes and functionalities. Currently, the annotations of a gene list are usually summarized by a table or a barplot. As such, potentially biologically important complexities such as one gene belonging to multiple annotation categories are difficult to extract. We have devised explicit and efficient visualization methods that provide intuitive methods for interrogating the intrinsic connections between biological categories and genes.

Findings

We have constructed a data model and now present two novel methods in a Bioconductor package, "GeneAnswers", to simultaneously visualize genes, concepts (a.k.a. annotation categories), and concept-gene connections (a.k.a. annotations): the "Concept-and-Gene Network" and the "Concept-and-Gene Cross Tabulation". These methods have been tested and validated with microarray-derived gene lists.

Conclusions

These new visualization methods can effectively present annotations using Gene Ontology, Disease Ontology, or any other user-defined gene annotations that have been pre-associated with an organism's genome by human curation, automated pipelines, or a combination of the two. The gene-annotation data model and associated methods are available in the Bioconductor package called "GeneAnswers " described in this publication.     

Integrated functional visualization of eukaryotic genomes

Background  

Increasing amounts of data from large scale whole genome analysis efforts demands convenient tools for manipulation, visualization and investigation. Whole genome plots offer an intuitive window to the analysis. We describe two applications that enable users to easily plot and explore whole genome data from their own or other researchers' experiments.     

Comparative genomics reveals birth and death of fragile regions in mammalian evolution

Background  

An important question in genome evolution is whether there exist fragile regions (rearrangement hotspots) where chromosomal rearrangements are happening over and over again. Although nearly all recent studies supported the existence of fragile regions in mammalian genomes, the most comprehensive phylogenomic study of mammals raised some doubts about their existence.     

CASSIOPE: An expert system for conserved regions searches

Background  

Understanding genome evolution provides insight into biological mechanisms. For many years comparative genomics and analysis of conserved chromosomal regions have helped to unravel the mechanisms involved in genome evolution and their implications for the study of biological systems. Detection of conserved regions (descending from a common ancestor) not only helps clarify genome evolution but also makes it possible to identify quantitative trait loci (QTLs) and investigate gene function.     

Identification of ATP binding residues of a protein from its primary sequence

Background  

One of the major challenges in post-genomic era is to provide functional annotations for large number of proteins arising from genome sequencing projects. The function of many proteins depends on their interaction with small molecules or ligands. ATP is one such important ligand that plays critical role as a coenzyme in the functionality of many proteins. There is a need to develop method for identifying ATP interacting residues in a ATP binding proteins (ABPs), in order to understand mechanism of protein-ligands interaction.     

ReseqChip: Automated integration of multiple local context probe data from the MitoChip array in mitochondrial DNA sequence assembly

Background  

The Affymetrix MitoChip v2.0 is an oligonucleotide tiling array for the resequencing of the human mitochondrial (mt) genome. For each of 16,569 nucleotide positions of the mt genome it holds two sets of four 25-mer probes each that match the heavy and the light strand of a reference mt genome and vary only at their central position to interrogate all four possible alleles. In addition, the MitoChip v2.0 carries alternative local context probes to account for known mtDNA variants. These probes have been neglected in most studies due to the lack of software for their automated analysis.     

ArrayIDer: automated structural re-annotation pipeline for DNA microarrays

Background  

Systems biology modeling from microarray data requires the most contemporary structural and functional array annotation. However, microarray annotations, especially for non-commercial, non-traditional biomedical model organisms, are often dated. In addition, most microarray analysis tools do not readily accept EST clone names, which are abundantly represented on arrays. Manual re-annotation of microarrays is impracticable and so we developed a computational re-annotation tool (ArrayIDer) to retrieve the most recent accession mapping files from public databases based on EST clone names or accessions and rapidly generate database accessions for entire microarrays.     

Regulated expression of a transgene introduced on an oriP/EBNA-1 PAC shuttle vector into human cells

Background  

Sequencing of the human genome has led to most genes being available in BAC or PAC vectors. However, limited functional information has been assigned to most of these genes. Techniques for the manipulation and transfer of complete functional units on large DNA fragments into human cells are crucial for the analysis of complete genes in their natural genomic context. One limitation of the functional studies using these vectors is the low transfection frequency.     

Tools for integrated sequence-structure analysis with UCSF Chimera

Background  

Comparing related structures and viewing the structures in the context of sequence alignments are important tasks in protein structure-function research. While many programs exist for individual aspects of such work, there is a need for interactive visualization tools that: (a) provide a deep integration of sequence and structure, far beyond mapping where a sequence region falls in the structure and vice versa; (b) facilitate changing data of one type based on the other (for example, using only sequence-conserved residues to match structures, or adjusting a sequence alignment based on spatial fit); (c) can be used with a researcher's own data, including arbitrary sequence alignments and annotations, closely or distantly related sets of proteins, etc.; and (d) interoperate with each other and with a full complement of molecular graphics features. We describe enhancements to UCSF Chimera to achieve these goals.     

A novel mode of chromosomal evolution peculiar to filamentous Ascomycete fungi

Background  

Gene loss, inversions, translocations, and other chromosomal rearrangements vary among species, resulting in different rates of structural genome evolution. Major chromosomal rearrangements are rare in most eukaryotes, giving large regions with the same genes in the same order and orientation across species. These regions of macrosynteny have been very useful for locating homologous genes in different species and to guide the assembly of genome sequences. Previous analyses in the fungi have indicated that macrosynteny is rare; instead, comparisons across species show no synteny or only microsyntenic regions encompassing usually five or fewer genes. To test the hypothesis that chromosomal evolution is different in the fungi compared to other eukaryotes, synteny was compared between species of the major fungal taxa.