BIOINFORMATICS APPLICATIONS NOTE
Vol. 23 no. 4 2007, pages 498–499
doi:10.1093/bioinformatics/btl618
Genome analysis
AutoGRAPH: an interactive web server for automating and
visualizing comparative genome maps
Thomas Derrien, Catherine André, Francis Galibert and Christophe Hitte
CNRS UMR6061 Génétique et Développement, Université de Rennes1, IFR140, 2 Av du Pr. Léon Bernard,
CS 34317, 35043, France
Received on September 20, 2006; revised and accepted on November 29, 2006
Advance Access publication December 4, 2006
Associate Editor: Alfonso Valencia
ABSTRACT
AutoGRAPH is an interactive web server for automatic multi-species
comparative genomics analyses based on personal datasets or
pre-inserted public datasets. This program automatically identifies conserved segments (CS) and breakpoint regions, assesses the conservation of marker/gene order between organisms, constructs synteny
maps for two to three species and generates high-quality, interactive
displays facilitating the identification of chromosomal rearrangements.
AutoGRAPH can also be used for the integration and comparison
of several types of genomic resources (meiotic maps, radiation
hybrid maps and genome sequences) for a single species, making
AutoGRAPH a versatile tool for comparative genomics analysis.
Availability: http://genoweb.univ-rennes1.fr/tom_dog/AutoGRAPH/
Contact: [email protected]
Supplementary information: A description of the algorithm and
additional information are available at http://genoweb.univ-rennes1.
fr/tom_dog/AutoGRAPH/Tutorial.php
1
INTRODUCTION
Many large-scale mapping and sequencing projects have been
completed in the last 10 years, making it possible to compare the
genomes of many species, to study evolutionary changes (Murphy
et al., 2005), and to improve genome annotation (Chatterji and
Pachter, 2006). Comparative genomics is based on the identification
of unique, unambiguous orthologous sequences in different species.
These sequences, known as comparative anchors (O’Brien et al.,
1993), are used to determine the contiguity of anchors between
genomes from different species and thus to investigate the correspondence of genomic segments and to define their limits.
Synteny maps can be used to identify conserved segments (CS),
corresponding to chromosomal segments containing the same list of
markers in all the species studied, and CS ordered (CSO), in which
not only are the same markers present in all species, but they are
also in the same order (Fig. 1). The genomic regions delimiting CS
and/or CSO, the breakpoints, can also be identified by constructing
synteny maps. Several tools have been developed for identifying
CS and CSO (Pan et al., 2005; Pavesi et al., 2004; Halling-Brown
et al., 2004; Clamp et al., 2003; Tesler, 2002). These tools allow
accurate comparative genomics analyses, but are often dedicated
to a specific genome, are not compatible with the use of large sets
of personal data, and are not always available online. We have
therefore developed AutoGRAPH, a versatile, online multi-species
To whom correspondence should be addressed.
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server for the automatic identification of CS, CSO, breakpoints,
marker/gene order conservation, the integration of multiple resources for a given species (Hitte et al., 2005) (Supplementary Figure 2),
and the generation of an interactive graphical display of comparative maps. AutoGRAPH frees the user from the tedious task
of plotting comparative maps and determining marker order correspondence manually for personal data, enabling the user to focus on
interpreting synteny or integrated maps.
2
PRINCIPLES
Using the AutoGRAPH server for constructing
synteny maps between species
Public datasets: information for the protein-coding genes (Ensembl
v39) of six reference mammalian genomes (human, chimpanzee,
cow, dog, mouse and rat) have been inserted into the program
database. Orthologous gene pairs with one-to-one relationships
(Ensembl v39) are used to construct pairwise or three-way synteny
maps. Synteny maps can be built for selected chromosomes or for
all the chromosomes of the reference genome. CS, CSO and breakpoints are automatically identified with the fast adjacency function.
This function assigns relative integers to the coordinates provided
and determines the sequence of integers in the same order for
common anchors of the reference and tested genomes (a detailed
description is provided in the Supplementary material). Various
options are available and can be combined interactively to specify
the way in which the synteny map should be constructed. For
example, it is possible to specify the nature of the orthology between
markers (one-to-one/one-to-zero) and the number of anchors defining CS and CSO. An adjacency penalty value, corresponding to the
number of marker that account for an interruption of colinearity can
be set by users to specify the marker order conservation criteria.
The program output consists of
A figure showing gene order relationships by means of connecting
lines within each CS and CSO, across two to three species, and
identifying the evolutionary breakpoint regions delimiting CS and/
or CSO (Fig. 1A). Ouput figure can be exported in several formats.
Two modes, making it possible to construct comparative maps
with or without one-to-zero relationship anchors, to switch the
orientation of each map and to scale images by a factor of
0.5 to 2 (Fig. 1B). When mode 1:0 is selected, genes in the
reference genome with no ortholog in the tested genome are
placed on the synteny map. Their putative interval location in
Ó The Author 2006. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected]
AutoGRAPH: an interactive web server
Fig. 1. Examples of AutoGRAPH output. (A) Graphical display of a three-way synteny map. Chromosome 34 from dog, the reference species, is represented in
the middle of the figure. The bar on the right corresponds to the human genome and the bar on the left to the mouse genome. For each species, markers are
identified by their ID and genomic coordinates. A dynamic link (orange box) provides a link to the Ensembl database for a complete gene description. The colored
lines connecting orthologous genes show the conservation of gene order. Black lines between colored segments represent breakpoints between CS and/or CSO
(see tutorial on the web server site). (B) This panel shows the options that can be set by users for the interactive definition of parameters for comparative genomics
analysis. (C) For all analyses submitted, CS, CSO and breakpoints are identified and characterized in terms of their chromosomal limits, size and marker
content, ID and density. All information can be downloaded in text file format.
the tested genome is inferred from the gene-order conservation
rule and is automatically output as a tabulated text file.
A table listing all CS, CSO and breakpoints, with their size, number of genes, chromosome coordinates and gene density (Fig. 1C).
Personal datasets: two formats of input datasets can be uploaded.
GFF format and tabular plain-text columns comprising unique marker IDs, chromosome number and genomic coordinates for each
dataset to be studied. Input datasets may contain different sets of
markers, with missing or duplicated markers or genes. Personal
datasets can be entered or uploaded via web form and example
inputs are provided by the web interface.
For comparative studies between species, synteny maps can be
built for entire chromosomes, specific parts of chromosome or the
whole genome, as specified by the user. Datasets for a single species
can also be used. Any type of coordinate-base pairs (bp) kilobases
(kb) or megabases (Mb)-mapping data units, centimorgans (cM) or
centirays (cR) can be used to indicate location in the genome. For
example, (Supplementary Figure 2), the server can integrate highdensity genetic/radiation hybrid/genome sequence maps for a single
species, facilitating map construction and improving sequence
assembly. Various options can be combined to specify comparative
analyses. The output displays are the same as for public datasets.
3
SYSTEMS
AutoGRAPH runs on a Apache web server and uses a MySQL
relational database. MySQL specific queries and Perl functions are
used to apply options and the adjacency function. The web interface
was developed in PHP language and the graphical display uses a
GD graphic library written in C (http://www.boutell.com/gd/).
ACKNOWLEDGEMENTS
The authors would like to thank Denis Larkin and Simon de Givry for
testing AutoGRAPH and providing useful suggestions. The authors
also thank the GenOuest Bioinformatics Platform for hosting the web
server, the French Centre National de la Recherche Scientifique
(CNRS) for supporting this work and the Conseil Regional de
Bretagne for supporting T.D. with a fellowship.
Conflict of Interest: none declared.
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