Nucleic Acids Research, 2009, Vol. 37, Database issuePublished online 10 November 2008
AutDB: a gene reference resource for
Saumyendra N. Basu, Ravi Kollu and Sharmila Banerjee-Basu*
MindSpec Inc., 9656 Blake Lane, Fairfax, VA 22031
Received August 15, 2008; Revised October 8, 2008; Accepted October 14, 2008
Recent advances in studies of Autism Spectrum
Disorders (ASD) has uncovered many new candidate
genes and continues to do so at an accelerated
pace. To address the genetic complexity of ASD,
we have developed AutDB (http://www.mindspec.
org/autdb.html), a publicly available web-portal for
on-going collection, manual annotation and visuali-
zation of genes linked to the disorder. We present a
disease-driven database model in AutDB where all
genes connected to ASD are collected and classi-
fied according to their genetic variation: candidates
identified from genetic association studies, rare
single gene mutations and genes linked to syndro-
mic autism. Gene entries are richly annotated for
their relevance to autism, along with an in-depth
view of their molecular functions. The content of
AutDB originates entirely from the published scien-
tific literature and is organized to optimize its use by
the research community. The main focus of this
resource is to provide an up-to-date, annotated list
of ASD candidate genes in the form of reference
dataset for interrogating molecular mechanisms
underlying the disorder. Our model for consolidated
knowledge representation in genetically complex
disorders could be replicated to study other such
Autism (MIM 209850) is a broad-spectrum multifactorial
condition with onset in the first years of life persisting
throughout the lifetime (1). A triad of deficits in the
areas of social communication, language development,
repetitive activities and restricted range of interests
define the core symptoms used in the diagnosis of
autism (DSM IV, 1994). Autism Spectrum Disorders
(ASD) is a commonly used term to cover the wide varia-
tions of autism. The dramatic rise in the prevalence of
ASD in recent years is of major public concern (2,3).
A strong genetic component underlying ASD is firmly
established from various lines of studies (4–7). The search
for ‘causative’ gene(s) has resulted in >10 whole genome
scans reporting numerous putative linkage regions for
ASD susceptibility (8,9). Genetic association studies
have identified many candidate genes for ASD (10–12);
however, many candidates fail to replicate between studies
and populations. In a minor proportion of cases, chro-
mosomal aberrations have been identified (13). Recently,
submicroscopic copy number variations (CNVs) were
strongly associated with ASD (8,14,15). Additionally,
ASD is consistently associated with a number of specific
genetic disorders such as Fragile X syndrome amongst
others (16,17). Single-gene mutations are also linked to
rare cases of ASD (18,19). The high genetic heterogeneity
of ASD poses an enormous challenge for understanding
We have developed an autism gene database, AutDB,
for ongoing cataloguing of genes linked to the disorder.
Our model for representing genetic knowledge encom-
passes collecting all types of genes including monogenic
and risk-conferring candidates linked to ASD. We have
implemented an integrated informatics approach to richly
annotate the candidate genes for their relevance to autism,
as well as an in-depth view of molecular functions. The
focus of this resource is to provide up-to-date, annotated
list of ASD candidate genes to serve as reference datasets
to understand disease biology. To the best of our knowl-
edge, this is the first example of an integrated gene data-
base for a genetically complex disorder.
DISEASE-SPECIFIC KNOWLEDGE MODEL
AutDB was designed and developed as an integrated,
disease-driven database model where both monogenic
and small risk-conferring candidates associated with
ASD are collected and annotated with diverse information
(Figure 1). In this resource, ASD-related genes are classi-
fied into four categories including three genetic categories
based on the type of genetic variation: (i) rAut: This cate-
gory includes genes implicated in rare monogenic forms
of ASD. The types of allelic variants within this
*To whom correspondence should be addressed. Tel: +1 703 938 0161; Fax: +1 703 938 5325; Email: email@example.com
? 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/
by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
disruptions/mutations directly linked to ASD, together
encompassing single-genes specific for ASD. (ii) sAut:
Genes implicated in syndromic forms of autism where a
sub-population with a specific genetic syndrome develops
autistic symptoms (iii) iAut: Small risk-conferring candi-
date genes with common polymorphisms identified from
genetic association studies in idiopathic ASD, and (iv)
fAut: Functional candidates relevant for ASD biology,
not covered by any of the other genetic categories.
However, it is possible that a gene can belong to more
than one category depending on the mutation; a
common variant conferring risk for developing idiopathic
autism, while an inactivating mutation in the same gene
placing it in higher risk-conferring categories. In such
cases, all categories are used to annotate the genes. Both
rAut and sAut categories represent monogenic forms of
Figure 1. (A) An integrated model for collection, annotation, storage and visualization of candidate genes for ASD. (1) Candidate genes for ASD are
compiled and maintained from an exhaustive search of scientific literature in the PubMed database maintained at NCBI (2) ASD candidates are
classified into four categories. (3) Entries are organized in the database for search and retrieval. (4) User-friendly display of candidate genes at two
levels for display and easy access with links to various external databases. (B) Search and display of candidate genes in AutDB. A search box is used
to retrieve ASD candidate genes catalogued in AutDB using various gene attributes. The search results are displayed at two levels. At level 1, the
gene entry is displayed in the summary row format showing: (A) gene symbol, (B) gene name, (C) chromosomal location, (D) Genetic category,
(E) GAD and (F) OMIM links where available, (G) Number of autism-specific studies, (H) primary PubMed reference and (I) detail/edit button.
A level 2, the entry is further displayed at a detail level in three-tier format showing: (1) gene summary with links to external databases such as
Entrez Gene and UniProt, (2) relevance for autism displaying candidate gene report summary and (3) references arranged under three sub-headings:
references for the candidate gene reports, highly referred and recent studies of the candidate genes.
Nucleic Acids Research, 2009,Vol. 37,Database issueD833
ASD, however, we made a distinct class for each based on
the fact that rAut genes were identified in the course of
screening for genetic variants in individuals diagnosed
with ASD. In contrast, ASD is diagnosed secondary to
the main clinical features of the specific genetic disorder
within the syndromic forms. An additional category of
functional candidates (fAut) extracted from reports link-
ing a gene/protein to the biology of ASD, are also
included in this resource and annotated accordingly.
AutDB: THE AUTISM GENE DATABASE
The content of AutDB originates entirely from published
scientific literature and is manually annotated by expert
biologists. A comprehensive collection of ASD-related
genes was initially compiled from an exhaustive search
of the scientific literature from PubMed database at
NCBI (http://www.ncbi.nih.gov/pubmed), followed by
timed-searches to maintain an up-to-date resource (see
Methods section for details). An AutDB entry is a candi-
date gene linked to ASD with all its attributes. The steps
involved in the process for curation of an AutDB entry are
schematically shown in Figure 1. First, all reports pertain-
ing to a candidate gene are extracted, counted for the
number of studies and collapsed under a single header
representing the gene entry. Second, a multi-step annota-
tion strategy is implemented to incorporate diverse molec-
ular information about a candidate gene for assessment of
its relevance for ASD. To enhance functional knowledge
of a candidate gene, our annotation model also expands
entries by drilling down to highly cited articles on candi-
date gene/protein, together with recently published articles
to represent current knowledge of gene functions. This
feature of AutDB provides functional information of an
ASD candidate gene beyond the basic information avail-
able in large public databases. Finally, candidate genes are
classified based on the type of genetic category according
to AutDB knowledge model (described in the previous
section). An example of an annotated AutDB gene is
shown in supplementary Figure S1.
SEARCH AND DISPLAY OF AutDB DATA
Genetic information in AutDB can be searched and
displayed in several ways including complex Boolean
queries. A representative search result of AutDB is
shown in Figure 2. In this example, searching for ASD
candidate genes on Chromosome 2 will retrieve a compre-
hensive list of ASD candidate genes in a tabular format.
This list includes candidates reported from genetic asso-
ciation studies, together with rare single-gene mutations
and functional candidates. Searching by gene name or
gene symbol will retrieve a gene entry that can be dis-
played at two levels (Figure 1B). At the first level of dis-
play in the summary row format, each entry is annotated
with gene symbol, gene name, chromosomal location,
genetic category and GAD and OMIM links where avail-
able, total number of autism-specific studies used to create
the entry in AutDB, together with a primary PubMed
reference reporting the candidate gene. Each entry is
further displayed at a detail level showing (i) gene sum-
mary with links to external databases such as Entrez Gene
(http://www.ncbi.nlm.nih.gov/sites/entrez) and UniProt
(http://www.uniprot.org/) to provide standardized generic
information on candidate genes, (ii) relevance for autism
showing autism-specific information describing the type
of genetic variants linked to ASD and the studies report-
ing the gene and (iii) references arranged under three sub-
headings. First, references linking the gene to ASD are
displayed. A primary reference in AutDB is defined as
the first positive report linking the candidate gene to
ASD. Next, highly referred studies on the candidate
gene extracted using Google scholar based on number
of citations are shown. Finally, references for recent stu-
dies pertaining to the candidate genes extracted from
timed-search of PubMed are also provided. A flow-chart
describing the search and display of an AutDB entry
is shown in Figure 1B. Annotated list of ASD candidate
genes can also be obtained from AutDB to serve as
These reference datasets provide global attributes of
ASD-linked genes and define an entry point for further
enhancement and optimization based on specific research
AutDB has been developed to provide current knowledge
on candidate genes linked to ASD and their relevance for
the disorder. We have adopted several novel strategies to
design the resource with the focus on gene functions. For
example, each candidate gene is annotated with highly
referred citations, together with recent recommendation
to provide a panoramic view of gene function. In our
view, AutDB annotation model can be applied to anno-
tate protein entries in other databases. Compared to other
www.alzforum.org/res/com/gen/alzgene/), which collects
only candidates identified from genetic association studies,
our integrative model includes all types of genetic varia-
tions implicated in ASD. A recent search of OMIM data-
OMIM) for genes linked to autism retrieved ?60 entries
(August, 2008), compared to 133 entries in AutDB as of
this writing. A recent review article lists 26 candidate genes
(12), thereby affirming that without a systematic and sus-
tained effort it is difficult to keep up with the rapidly
evolving field of autism biology. The first rare single
gene mutation in ASD was reported in 2003 (18), however,
in the last two years with the application of genomic tech-
nologies, a steady stream of single gene mutations in
ASD is reported in the scientific literature (15,20). Con-
sequently, the balance is shifting between reported single-
gene mutations and candidates identified from genetic
association studies. The current trend in autism genetics
validates the integrative model in AutDB.
Our major focus is to provide a filtered, annotated
reference set of ASD-linked genes to the research com-
munity for immediate application in the areas of (i) build-
Nucleic Acids Research, 2009, Vol. 37, Databaseissue
(manuscript in preparation) and (ii) systems-level analysis
of various molecular data to gain insight into the etiology
Autism, a rare encounter in mid last century, is becoming
Accumulating evidence strongly point towards many
genetic causes can contribute to the development of
ASD. In practical terms, the number of articles reporting
putative candidate loci, as well as high throughput array-
based studies reporting many loci in a single publication
are rapidly accumulating. We have created AutDB to
bridge the gap between the vast amount of information
embedded in the scientific literature and consolidated
knowledge representation of ASD for molecular analysis.
Lastly, the dynamic nature of this database provides a
window into the current state of research to aid in the
early diagnostics and therapeutics for individuals with
the lasttwo decades.
Designof an integratedplatform
AutDB is a portal developed in JAVA on the J2EE plat-
form on Linux with an Relational Database Management
System (RDBMS) backend as its repository. The portal
for AutDB is designed to be extensible where newer mod-
ules could be incorporated with relative ease by configura-
tion. The application is deployed as a webapps in the
Tomcat Application server connecting to the RDBMS.
Connection pooling is provided by the Application
Server, which greatly decreases the load on the system
and enhances the performance. It also connects to the
NLM database with the help of their DTDs and collects
relevant information from the NLM databases for the end
user. Apart from batch mass updates and new additions
through database load programs, AutDB also provides
interfaces for online updates restricted by user roles.
Most importantly, AutDB provides interfaces within the
Autism research community for co-operative, moderated
annotations and curations for deeply annotated genes or
gene sets. A search engine is provided on different
Figure 2. Online display of AutDB search results. (A) Searching for candidate genes on Chromosome 2 retrieved an annotated list of ASD candidate
genes in Chromosome 2.
Nucleic Acids Research, 2009,Vol. 37,Database issueD835
attribute names on their applicable data sets to build Download full-text
queries at varying degrees of complexity.
Development of AutDB
genes. To collect ASD candidate genes for the first release
of AutDB, we performed a comprehensive search of all
articles in the PubMed database maintained at NCBI
search&DB=pubmed). The search terms included ‘gene’
AND (‘autism’ OR ‘autistic’) restricted to the titles and
abstracts of the publications for retrieval. Furthermore,
candidate genes listed in review articles on molecular
genetics of ASD, along with cross-references therein,
were mapped and added (if new) to our candidate gene
list from PubMed searches to compile the most exhaustive
gene set. After the first release, starting from June 2006, a
daily semi automated search of the PubMed with the same
keywords is implemented to maintain an up-to-date
resourceof all candidate
Additionally, relevant journal articles in the fields of
genetics, neurobiology, and psychiatry are screened on a
regular basis to enrich the resource.
To select the primary reference for a candidate gene, the
first positive report linking the gene to (ASD) was
searched in PubMed. However, to select the primary refer-
ence for a ‘Syndromic autism’ gene where a large number
of reports are published connecting the syndrome to
autism, we adopted the following steps: First, google scho-
lar is used with the criteria [(autism OR autistic) AND
‘syndrome name’ AND ‘gene name’] to search for the
most highly cited reports. Next, a primary reference is
selected among these highly cited reports by reading the
article (see Supplementary Table 1).
storageand categorization ofcandidate
Supplementary Data are available at NAR Online.
Funding for open access charge: MindSpec Inc., a non-
profit organization dedicated to autism research.
Conflict of interest statement: MindSpec and Sharmila
Banerjee-Basu hold the license for AutDB.
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