<title>1. INTRODUCTION</title> <p>The TreeGenes database is a resource for all forest trees, however work
to date has focused on specific members of the Pinaceae family. Pinaceae is one
of eight families of the order Coniferales (conifer) and includes 10 genera and
approximately 220 species. Species of Pinaceae are commercially important to
the forest industry and are used for building, packaging, and paper products
worldwide. Because of the very large size and complexity of the conifer genomes
(10–40 Gb) [##UREF##0##1##], greater emphasis has been placed on the expressed portion of the
genome. This has been achieved through EST and large-scale resequencing
projects. The principal species
represented include six members of the genus <italic>Pinus</italic> (<italic>taeda</italic>, <italic>elliottii, radiata, pinaster, sylvestris</italic> and <italic>lambertiana</italic>), two species from other
genera of the Pinaceae (<italic>Picea abies</italic> and <italic>Pseudotsuga menzeisii</italic>), and one
member of another family of conifer (<italic>Cryptomeria
japonica</italic> Cupressaceae). Recent work
has also focused on integrating resources for members of Populus and
Eucalyptus. Developing genetic resources for these organisms improve the
genetic understanding individual member species within the same families or
genera. The rapid rate in 
which genetic data is being generated from large-scale EST and resequencing
projects has required corresponding growth in relational databases and
associated computational tools. The ability to
combine data from different sources facilitates interpretation and potentially
allows stronger inferences to be made. When information from several different
databases is required, the assembly of data into a format suitable for querying
is a challenge. The development of systems for the integration and combined
analysis of diverse data remains a priority in bioinformatics. The TreeGenes database helps
researchers efficiently analyze, access, integrate, and apply the data. This paper will navigate through the Dendrome
(<ext-link ext-link-type="uri" xlink:href="http://dendrome.ucdavis.edu/">http://dendrome.ucdavis.edu/</ext-link>) and TreeGenes (<ext-link ext-link-type="uri" xlink:href="http://dendrome.ucdavis.edu/treegenes/">http://dendrome.ucdavis.edu/treegenes/</ext-link>) interfaces as well as the
types of data that can be accessed through these resources.</p>
<p>Recommended by Shizhong Xu</p> <p>The Dendrome Project and associated TreeGenes database serve the forest genetics research community through a curated and integrated web-based relational database. The research community is composed of approximately 2 000 members representing over 730 organizations worldwide. The database itself is composed of a wide range of genetic data from many forest trees with focused efforts on commercially important members of the Pinaceae family. The primary data types curated include species, publications, tree and DNA extraction information, genetic maps, molecular markers, ESTs, genotypic, and phenotypic data. There are currently ten main search modules or user access points within this PostgreSQL database. These access points allow users to navigate logically through the related data types. The goals of the Dendrome Project are to (1) provide a comprehensive resource for forest tree genomics data to facilitate gene discovery in related species, (2) develop interfaces that encourage the submission and integration of all genomic data, and to (3) centralize and distribute existing and novel online tools for the research community that both support and ease analysis. Recent developments have focused on increasing data content, functional annotations, data retrieval, and visualization tools. TreeGenes was developed to provide a centralized web resource with analysis and visualization tools to support data storage and exchange.</p>
<title>2. CONTENT AND ORGANIZATION</title> <title>2.1. Dendrome project resources</title> <p>The Dendrome pages are entry points to valuable
links, community projects, information forums, custom tools, and the TreeGenes
database (<ext-link ext-link-type="uri" xlink:href="http://dendrome.ucdavis.edu/resources/">http://dendrome.ucdavis.edu/resources/</ext-link>)
(##FIG##0##Figure 1##). The resources
available include custom BLAST and FASTA services for sequence similarity
searches. These services directly access all publicly available sequence data
as well as custom EST or related databases. 
Users can submit requests for the generation and submission of a
searchable database to this repository. An area for the retrieval and
submission of custom scripts developed in the community of general use for the
manipulation of genetic data exists. 
This interface allows authors to post and make available scripts and
more advanced programs that they have designed including relevant
documentation. The <italic>tools</italic> pages are
internally curated and provide information on open source and freeware software
packages that are relevant to the processing, availability, and analysis of
data presented in the TreeGenes database. Links’ pages allow users to submit to and describe online resources and projects
relevant to the research community. The links are submitted into one or more
relevant genomic categories and are available immediately in the
repository.Forms are present through the Dendrome site in order to encourage users to modify, add, and correct a variety of information. The Dendrome pages are the primary source
of useful information for the research community such as upcoming events,
research opportunities, and the community-curated repository of links. In
addition, a discussion forum has recently been implemented to encourage users
to submit questions and comments on the database as well as participate in
general discussions of conifer genomics. The related Dendrome Plone
(<ext-link ext-link-type="uri" xlink:href="http://dendrome.ucdavis.edu/TGPlone">http://dendrome.ucdavis.edu/TGPlone</ext-link>), based on the Plone 3.0 content
management platform (<ext-link ext-link-type="uri" xlink:href="http://plone.org/">http://plone.org/</ext-link>),
provides a user friendly environment for investigators to share and obtain
information relating to a variety of projects.</p> <title>2.2. Treegenes database overview</title> <p>TreeGenes (<ext-link ext-link-type="uri" xlink:href="http://dendrome.ucdavis.edu/treegenes/">http://dendrome.ucdavis.edu/treegenes/</ext-link>) functions through a semi-automated PostgreSQL
version 8.1.4-based
database that consists of modules to hold a broad range
of data and information for trees. This system has a front end consisting of
Perl 5.8.5 scripts running in a Linux/Apache/PHP environment. The database is
organized into ten different modules that are highly connected in order to ease
access and analysis of the data (##FIG##1##Figure 2##). These modules include sample
tracking that holds tree source and DNA extraction information. The sequencing
and primers module contains sequences from the resequencing efforts as well as
data describing how the sequences were generated and parameters used in their
alignment and analysis. The Species module holds the taxonomy information and
the Colleague Module contains information on laboratories and individuals.
There is a comparative map module that uses Cmap [##REF##11752266##2##] to hold and view genetic
maps, map relations, and molecular markers. The Literature module stores
publications. The EST module stores sequence and annotation information and
ties into an automated pipeline that allows users to submit sequences for
processing, analysis, and Genbank submission. TreeGenes is being expanded to
include more extensive genotype and phenotype data utilizing data models from
the Germinate database [##REF##16219922##3##]. This organization allows for a combination of
internal curation as well as third-party submissions to validate and maintain
current content.</p> <title>2.2.1. Species module</title> <p>Individual species and colleague
databases exist in the TreeGenes schema and are well integrated with other
database modules. Species is a manually
curated database of 222 members of the Pinaceae family. It is currently being
expanded to encompass more forest trees. 
The Species module contains detailed information for each entry
including range maps and multiple images for each tree. Internal connections to the researchers who
study each species, moreover, relevant publications are available in the detail
view. External links to NCBI’s extended
taxonomy [##REF##14681350##4##] provide direct access to publicly available sequence sets.</p> <title>2.2.2. Colleague module</title> <p>The colleague database is a
semi-automated directory of nearly 2 000 researchers and 730
organizations. The colleague interfaces
allow users to add, modify, and remove the contact information of both the
users themselves and their respective organizations. The interface offers the user the ability to
query researchers who focus on particular species in addition to their specific
research interests.</p> <title>2.2.3. Comparative maps module</title> <p>The comparative map module is
displayed through a modified version of Cmap [##REF##11752266##2##]. Cmap is one component of the larger Generic
Model Organism Database (GMOD) toolkit [##REF##12368253##5##]. 
This package has the ability to compare across genetic, sequence, and
physical maps. At this time, TreeGenes
only contains genetic maps. The
interactive display allows individuals to select single maps and continue to
add additional linkage groups from any species to build a comparative
view. Maps can be selected by specific
linkage groups or they can be queried by their features. TreeGenes currently houses features (marker
types) for over 50 genetic maps including AFLP, ESTP, Isozyme, SSR, RAPD, and
RFLP. The final map display is highly interactive. Selecting specific features
allows for the display of marker information and sequence information. Detail views also include links to internal
databases within TreeGenes including species, literature, colleague, EST, QTLs,
and PCR primer information (##FIG##2##Figure 3##). A
standardized nomenclature has been developed to describe each potential map
feature. Custom scripts exist to
generate and enforce this documented nomenclature during the import
process. This internal validation allows
for name-based correspondences (markers) to be annotated. These correspondences can be easily viewed
during comparisons of the maps themselves as well as Cmap’s matrix view.</p> <title>2.2.4. Literature module</title> <p>The Literature module is
responsible for performing regular and automated searches of major relevant publication
repositories including Pubmed [##REF##10455581##6##] and Biosis according to a compiled list of
keywords. TreeGenes organizes these
publications, creates a list of searchable keywords, and builds internal
relations to provide a centralized forest genetics publication repository. This resource can be queried on many levels
and allows for a customized subscription to preview recently added
publications. In addition to querying
public repositories, TreeGenes has a unique feature that allows for the
submission of manuscripts by the author. 
These submitted publications undergo the same process of keyword
generation. In addition to the
submission of new publications, authors are encouraged to submit supplemental
information. Each detail view provides
automated external linking in addition to the opportunity to provide sequence data, raw mapping files, or accession numbers from
public database submissions. This is the
primary mechanism by which the curators can organize the information and
further populate the related modules. 
All standardized nomenclatures are enforced during submission including
accessions IDs and TreeGenes comparative mapping nomenclature.</p> <title>2.2.5. Expressed sequence tags module</title> <p>The TreeGenes EST pipeline and database apply a combination of custom and open-source tools integrated into a
fully automated processing pipeline (##FIG##3##Figure 4##). 
The processing occurs at five unique stages and allows users to either
original tracefiles or FASTA files. In
the latter case, the quality scores are unable to be considered in the
processing. (1) Specific EST
nomenclature is enforced during submission of the initial trace files or FASTA
text files. (2) Tracefiles are processed
to identify a filtered, high-quality clone library as determined by Ewing et al. [##REF##9521921##7##]. (3) Sequence clustering consists of assembling
high-quality sequences to produce longer transcripts and reduce overall
redundancy. This occurs via two rounds
of Cap3 [##REF##10508846##8##] processing. (4) Annotation
involves pairwise comparisons of the EST clone library and the EST contig
consensus sequences. Sequence identification and annotation is provided by a
series of BLAST homology searches (Parallel and Priority BLAST) against
user-defined and publicly available sequence databases implemented with NCBI’s
BLAST [##REF##18440982##9##]. In general, searches are
performed against the Genbank nr protein database [##REF##14681350##4##], however users may select
custom datasets. The UniGene dataset is derived by selecting the clone that best represents each contig and
the singletons that have unique or no matches are further annotated. This level of annotation consists of Gene
Ontology (GO) [##REF##10802651##10##] (with preference given to Plant GO [##REF##18629207##11##] hits when
available), KEGG for metabolic pathways [##REF##10928937##12##], Enzyme Commission (EC) [##UREF##1##13##], and
InterPro [##REF##12230031##14##] for conserved protein domains (which includes CDD [##REF##15608175##15##], SMART
[##REF##9847187##16##], and Pfam [##REF##11752314##17##]). The final stage
and optional stage of the processing pipeline involves submission to Genbank
[##REF##14681350##4##] following the approval of the owner. Users can login in and view the
original EST data, the cleansed data and the analysis results. Tables,
formatted text, and links are provided for viewing summary and detailed
information. Submission includes the generation, formatting, and actual
submission of the required flat files. 
Since the TreeGenes database is home to many species, the database is
organized to maintain independent species and project sets while search
interfaces have been developed to support comparative queries.</p> <title>2.2.6. Resequencing interface</title> <p>The Sample Tracking, Primers, Sequencing, and Genotype
modules are currently accessible through an interactive interface that includes
a growing library of predefined queries (##FIG##4##Figure 5##). Each template provides a
simplified view of an underlying query by means of a text description and one
or more searchable fields. The recent increase in high-throughput sequencing
projects encouraged the development of interfaces capable of dealing with the
analysis of large amounts of data. In
short, researchers can query thousands of sequences in a single operation. The desktop
style interface assists with these searches and allows users to customize their
results and organize data views. Users can perform multiple searches at one
time and combine results. Data types
available here currently include ESTs, EST annotation, tracefiles, SNPs, primer
sequences, and resequenced amplicons (including DNA extraction and tree sample
information) (<ext-link ext-link-type="uri" xlink:href="http://dendrome.ucdavis.edu/interface/">http://dendrome.ucdavis.edu/interface/</ext-link>). 
This interface currently accesses information for over 40 000 ESTs and nearly 8 000 resequenced amplicons.</p> <title>3. AVAILABILITY, DATA SUBMISSION,
FEEDBACK, AND SUPPORT</title> <p>The Dendrome Project and
the TreeGenes database are publicly available and can be accessed at <ext-link ext-link-type="uri" xlink:href="http://dendrome.ucdavis.edu/">http://dendrome.ucdavis.edu/</ext-link>. From the website, there is access to help in
the form of tutorials and a user manual. We
encourage researchers to actively participate in making Dendrome and TreeGenes
more accessible by submitting data and providing feedback on general usability.
We are interested in being able to provide a unique resource to the community,
which is fully dependent on individual submissions. TreeGenes has a robust
interface to submit a variety of information including sequence data and
comparative mapping files through the literature database. More information on
this resource can be found in <ext-link ext-link-type="uri" xlink:href="http://dendrome.ucdavis.edu/TreeGenes/literature/">http://dendrome.ucdavis.edu/TreeGenes/literature/</ext-link>. The discussion forum available through the Dendrome Project
website provides an opportunity for users to submit suggestions on improvements
or additions to the community resources. Input relating to new functionality and additional data
sources are welcome here. A help form is available for user-specific queries.
This feedback form will automatically send us the inquiry, making it easier to
give an accurate response. Further information is available by joining one of
the TreeGenes electronic mailing lists (details on the website) or by email to
<ext-link ext-link-type="uri" xlink:href="info@treegenes.ucdavis.edu">info@treegenes.ucdavis.edu</ext-link>.</p> <title>4. FUTURE DEVELOPMENT</title> <p>The structure of TreeGenes permits researchers to rapidly accumulate a
wealth of information about a particular object or set of objects. This
flexible design facilitates the formulation of new hypotheses for refining
subsequent investigations. In addition to refinement and extension of smaller
scale investigations, TreeGenes can also facilitate more comprehensive
approaches by allowing the investigation of interactions among datasets. TreeGenes is still in a phase of rapid development. Future plans include incorporating
standardized gene ontology to describe phenotypic traits unique to forest
trees. In addition, robust databases will be available for the submission and
visualization of SNP and expression data. 
The advanced workspace interface will be expanded to accommodate both of
these data types as well as tools to ease the analysis and comparison of this
information. With an emphasis on meaningful data acquisition and interface
design, TreeGenes continues to serve a critical role in the efficient storage
and analysis of data by the forest genetics community.</p>
<fig id="fig1" position="float"><label>Figure 1</label><caption><p>
<italic>Diversity of web-based resources available through the Dendrome
Project and TreeGenes database</italic>. The Dendrome project
(<ext-link ext-link-type="uri" xlink:href="http://dendrome.ucdavis.edu/">http://dendrome.ucdavis.edu/</ext-link>) serves as a community resource and
portal to a variety of resources. These include the TreeGenes
database followed by the supporting large-scale project pages, and
the Dendrome Plone which is a controlled access forum.</p></caption></fig> <fig id="fig2" position="float"><label>Figure 2</label><caption><p>
<italic>Modular view of the TreeGenes database schema</italic>. The TreeGenes
database (<ext-link ext-link-type="uri" xlink:href="http://dendrome.ucdavis.edu/treegenes/">http://dendrome.ucdavis.edu/treegenes/</ext-link>) is a fully
relational PostgreSQL database with a total of ten modules. These
modules have connections supported by interfaces that allow queries
across these data types. Current development is focused on fully
incorporating the genotype and phenotype modules.</p></caption></fig> <fig id="fig3" position="float"><label>Figure 3</label><caption><p>
<italic>Comparative mapping (CMAP) interface applied to Pinaceae</italic>. The
modified version of Cmap utilized to represent the genetic map unit
in TreeGenes is highly interactive. This interface allows for the
visualization of comparative map builds including matrix views that
display the correspondences between the map sets. Cmap’s internal
links also provide detailed supporting information on molecular
markers, primer sequences, species, and publications.</p></caption></fig> <fig id="fig4" position="float"><label>Figure 4</label><caption><p>
<italic>EST analysis and submission process</italic>. The EST processing and
submission pipeline can support multiple projects and species
(<ext-link ext-link-type="uri" xlink:href="http://dendrome.ucdavis.edu/treegenes/est/">http://dendrome.ucdavis.edu/treegenes/est/</ext-link>). Tracefiles are
renamed, assembled, clustered, annotated, and submitted to Genbank
upon the submitter’s approval. The web interface allows users to
track the progress, view EST sequences, and provide basic
annotation-based searches once the data has been loaded into the
TreeGenes database.</p></caption></fig> <fig id="fig5" position="float"><label>Figure 5</label><caption><p>
<italic>Resequencing interface</italic>. The workspace interface environment
allows for more complex, batch searches of EST, annotation,
tracefile, PCR primer, amplicon sequence, SNP, DNA extraction, and
tree sample data types (<ext-link ext-link-type="uri" xlink:href="http://dendrome.ucdavis.edu/interface/">http://dendrome.ucdavis.edu/interface/</ext-link>). Users can initiate searches based on any of these data types. The
data retrieved can be compiled into customized lists, saved for
future searches, and downloaded to a local machine for further
analysis.</p></caption></fig>
<graphic xlink:href="IJPG2008-412875.001"/> <graphic xlink:href="IJPG2008-412875.002"/> <graphic xlink:href="IJPG2008-412875.003"/> <graphic xlink:href="IJPG2008-412875.004"/> <graphic xlink:href="IJPG2008-412875.005"/>
[{"label": ["1"], "surname": ["Ahuja", "Neale"], "given-names": ["MR", "DB"], "article-title": ["Evolution of genome size in conifers"], "italic": ["Silvae Genetica"], "year": ["2005"], "volume": ["54"], "issue": ["3"], "fpage": ["126"], "lpage": ["137"]}, {"label": ["13"], "surname": ["Grisolia"], "given-names": ["S"], "article-title": ["Enzyme nomenclature"], "italic": ["Science"], "year": ["1961"], "volume": ["133"], "issue": ["3465"], "fpage": ["1672"], "lpage": ["1674"]}]
Int J Plant Genomics. 2008 Aug 18; 2008:412875