This document is designed to get the new user quickly started with AutDB Gene release 3.0, an integrated resource for autism research. The goal is to acquaint the user with the touch and feel of AutDB Gene, and provide enough information to search, view and begin using the database. However, this is not a comprehensive user manual describing all the functionalities of AutDB Gene.

We encourage you to use AutDB Gene and contact us with any comments or questions. We would be glad to hear from you.

Release note for AutDB Gene 3.0:

• A new module containing data on animal models for autism has been developed and integrated within the gene portal.  This configuration essentially links two different types of datasets: Human Genes and Animal models. 
• Please refer to Q&A # 10, 11, 12 and 13 in the Getting started section for detailed functionality of this module.

Release note for AutDB Gene 2.0:

• The content of AutDB Gene is freely available to any user.   
• A new functionality of “Edit a Gene” module has been added in AutDB Gene for submitting annotations to an existing candidate gene is AutDB Gene.  Please see Q&A # 9 in the Getting started section for detailed functionality of this module. 
• A registration is required to submit annotations in AutDB Gene.

Table of Contents

Getting started

1.         What is AutDB Gene?
2.         What types of information does AutDB Gene contain?
3.         What is the gene classification rationale in AutDB Gene?
4.         How is AutDB Gene data organized?
5.         How do I search AutDB Gene?
6.         What do I see in the search result?
7.         How do I see the detailed annotation of the candidate gene in AutDB Gene?
8.         What do I see in the detailed annotation of the candidate genes in AutDB Gene?
9.         How do I edit/submit annotations to a gene in AutDB Gene?
10.       How do I search for animal models in AutDB Gene?
11.       What do I see by searching for gene name “neuroligin” in the animal model dataset?
12.       How do I see in the detailed annotation of the animal model in AutDB Gene?
13.       What is PhenoBase?
14.       How do I cite the content of AutDB Gene?
15.       How do I contact AutDB Gene?

Getting started

1) What is AutDB Gene?

AutDB Gene is a publicly available, curated, web-based, searchable database for autism research. This resource is built on information extracted from the studies on molecular genetics and biology of Autism Spectrum Disorders (ASD).

The main focus of this resource is a comprehensive list of candidate genes associated with ASD.  The candidate genes are richly annotated for their relevance to autism, along with an in-depth, up-to-date view of their molecular function extracted from the current scientific literature.

2) What types of information does AutDB Gene contain?

AutDB Gene is 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 related to the gene.

A new animal model module has been developed and integrated within the gene portal so that the data can be searched and retrieved using a single search engine. This configuration essentially links two different types of datasets: Human Genes and Animal models. 

The content of AutDB Gene originates entirely from published scientific literature and is manually annotated by expert biologists.

3) What is the gene classification rationale in AutDB Gene?

ASD-related genes in AutDB Gene are classified into four categories including three genetic categories based on the type of genetic variation:

1. rAut: This category includes genes implicated in rare monogenic forms of ASD.  The types of allelic variants within this class include rare polymorphisms and single-gene disruptions/mutations directly linked to ASD, together with sub-microscopic deletions/duplications (CNVs) encompassing single-genes specific for ASD.
2. sAut: Genes implicated in syndromic forms of autism where a sub-population with a specific genetic syndrome develops autistic symptoms
3. iAut: Small risk-conferring candidate genes with common polymorphisms identified from genetic association studies in idiopathic ASD
4. 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 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 linking a gene/protein to the biology of ASD, are also included in this resource and annotated accordingly.

4) How is AutDB Gene data organized?

The steps involved in the process for curation of an AutDB Gene entry are schematically shown in Figure 1. First, all reports pertaining 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 annotation strategy is implemented to incorporate diverse molecular 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 candidate gene/protein, together with recently published articles to represent current knowledge of gene functions. This feature of AutDB Gene provides functional information of an ASD candidate gene beyond the basic information available in large public databases.

An AutDB Gene entry is a candidate gene linked to ASD with all its attributes.

Figure 1. An integrated model for collection, annotation, storage and visualization of candidate genes linked to ASD.

5) How do I search AutDB Gene?

Using the drop-down menus within this search box, the user can specify a number of search parameters.

The first menu allows the user to select the type of information i.e., dataset that will be searched. Each dataset in AutDB Gene has data fields relevant to the particular type of study, incorporating as much quantitative information as possible.

The second menu is to choose search fields in the selected dataset from the drop-down menu for the type of user query. 

Next, query term/phrase is entered in the empty text window of the search box.  The last step is to submit the query for searching AutDB Gene.

Figure 2.  Search fields in Human Gene datasets

Example for searching for candidate genes linked to ASD:

1.  Select a Dataset:   Human Gene
2.  Search fields for:   Gene Symbol: CACNA1C
3.  Submit query
The above query translates into:  Search for candidate gene CACNA1C

 Figure 3. AutDB Gene search box. Queries are formed by selecting a dataset and search fields in from the drop-down menu

In this example, searching for ASD candidate genes on Chromosome 2 will retrieve a comprehensive list of ASD candidate genes in a tabular format. This list includes candidates reported from genetic association studies, together with rare single-gene mutations and functional candidates.
 

Figure 4: Display of search results for ASD-linked genes on Chromosome 2. 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, (G) primary PubMed reference and (I) detail/edit button.  A level 2, the entry is further displayed at a detail level in three-tier format.

7) How do I see the detailed annotation of the candidate gene in AutDB Gene?

Selecting the gene symbol or the detail box in the search result table will take you to the detailed annotation page.

Figure 5.  The detailed annotation of a candidate gene can be accessed from the summary line display

8) What do I see in the detailed annotation of the candidate gense in AutDB Gene?

The detailed annotation of the candidate gene has three sections to provide an overview of gene function.

The sections are as follows:

1.  Gene Summary
The summary section provides standardized generic information on candidate genes with links to major external databases such as Entrez Gene (http://www.ncbi.nlm.nih.gov/sites/entrez) and UniProt (http://www.uniprot.org/).

2.  Relevance to autism
This section provides the support studies connecting the gene to ASD.
                       
3.  References
This section includes the citations for the support studies connecting the gene to ASD.  Additionally, in order to provide panoramic view of the gene/protein function, the reference section also includes studies that are:
A.  Highly referred, not limited only to the field of autism research.
            B.  Recent interesting recent work on the gene/protein, not limited only to the field of autism research (Recent recommendation)

Figure 6. Detail level display of an AutDB Gene entry, SLC25A12. Support studies pertaining to a candidate gene are collapsed into a single entry and formatted and linked to the PubMed abstracts of the source articles.

9) How do I edit/submit annotations to a gene in AutDB Gene?

 A registration with AutDB Gene is required to access the edit module of AutDB Gene. 

The ”Edit a Gene” function of AutDB Gene provides an opportunity to a registered user to edit or add new annotations to an existing gene entry. The edit function can be evoked from the summary row display of a gene entry (Figure 5, panel A). This step brings up a submission window to add annotations (Figure 5, panel B).  The submitted annotations are sent to a moderator for approval.  Upon approval, the submitted annotations are formatted and displayed as shown in Figure 5, panel C.

 Figure 7.  Editing a gene entry in AutDB Gene.  A.  Summary row display of a syndromic candidate gene, FMR1, fragile X mental retardation 1.  B.  New annotations are submitted by evoking the edit function of a candidate gene. In this example, PubMed identifiers of two recently published articles on FMR1 are submitted as new annotations.  C.  Display of new annotations within “Recent Recommendation” category of detailed display of an AutDB Gene entry.

 10) How do I search for animal models in AutDB Gene?

From the search page, the user can select the “Animal model” from the dataset selection menu. This action will invoke data fields specific for the animal model module. The information on animal models can be searched and displayed in several ways including complex Boolean queries. Additionally, the animal model dataset can also be searched by model types or phenotype categories that are relevant for the biology of ASD.

Figure 8.  Searching for animal models in AutDB Gene

11) What do I see by searching for gene name “neuroligin” in the animal model dataset

In this example, searching for animal models with the gene name “neuroligin” will retrieve a comprehensive list of models in a tabular format. 

Figure 9.  Searching for neuroligins in the animal model dataset. The search results are displayed in a summary row format showing: (A) gene symbol, (B) gene name, (C) model species, (D) syntenic, (E) Primary Reference,  (F) Number of Reports, (G) Number of models, (H) Human ASD Study and (I) detail/edit button.

12) What do I see in the detailed annotation of the animal model in AutDB Gene?

Selecting the gene symbol in the search result table will take you to the detailed annotation page. Animal model entries are displayed at three levels. At the first level of display in the summary row format, each entry is annotated with gene symbol, gene name, model species, Syntenic, total number of model reports, total number of animal models, together with a primary PubMed reference reporting the generation of the model for the candidate gene. Additionally, within the summary line display, a link is provided to the human ASD study for the corresponding gene. Each entry is further displayed at a detail level (Figure 10, level II) showing (i) gene summary with links to external databases such as MGI (http://www.informatics.jax.org) and Allen Brain Atlas (http://www.brain-map.org/), (ii) References, and (iii) List of animal models. Finally at the third level (Figure 10, level III), for each model, the extended phenotypic profile is organized under 16 categories that are relevant for the biology of ASD (Q 13, Table 1).  The animal model phenotype is  shown as changes observed, no changes or not reported.

13)What is PhenoBase?

PhenoBase is a key component of the animal model module serving as a repository of standardized phenotype terms and their definitions for annotating the animal models. PhenoBase combines core behavioral domains of autism, along with in-depth physiological and molecular characteristics reported in the animal studies. It is a high-level classification scheme encompassing 16 broad categories relevant for clinical presentation of autism. It includes >100 terms organized within these 16 major categories. Table 1. Phenotypic categories for annotating animal models related to autism.

14) How do cite the content of AutDB Gene?

AutDB: a gene reference resource for autism research.
Basu SN, Kollu R, Banerjee-Basu S.
Nucleic Acids Res. 2009 Jan;37(Database issue):D832-6. Epub 2008 Nov 10.
PMID: 19015121

 15) How do I contact AutDB Gene?
Please send EMAILS to info@mindspec.org

Appendix A.  Semantics of the column headers for candidate genes