AutismKB 2.0 interface contains six main menus, i.e. Home, Data, Tools, Search, Manual and Contact that will help users to find the information they need.

i. The home page shows the ASD definition, prevalence, core symptoms, collected evidences and total data statistics. At the same time, it provided seven kinds of quick links for main datasets.

ii. The data menu contains four options, i.e. Browse by Categories, Browse by Method, View Mosaicism, Download Datasets. For categories, there were genetic and syndromic categories.

iii. The tools menu contains two options, i.e. Ranking Tool (a gene scoring algorithm tool) and Enrichment Analysis (an enrichment analysis tool). Among them, tool for enrichment analysis is newly added. Enrichment analysis is based on KOBAS (43), and enable users to view and download the enriched functional categories from the queried gene lists.

iv. The search page contains three options, i.e. simple query, advanced query and batch query. The search engine is able to tell whether the input is a gene symbol or a SNP id.

a) Firstly, simple query. Twelve input types are supported under the simple query. They are partial gene symbol/name, gene official symbol, gene full name, Entrez gene id, Ensemble id, Uniprot id, SNP id, SNP name, CNV id, linkage id, location and PubMed id. Simultaneously, users only need to enter the prefix of a gene’s name and an asterisk. For example, if users want to search all the information about genes whose names begin with “TS”, they can input “TS*”. The output webpage would show the genetic information for all the genes that begin with TS.

b) Secondly, users can freely choose a variety of types of genetic information for cross-searching under the advanced query mode. For example, users can set chromosome coordinates, evidence score range, ethnic, evidence types, literature title or abstract and published id to find information of certain genes.

c) Thirdly, batch query. Users can enter multiple gene symbols, Entrez gene ids, SNP ids or PubMed ids at the same time under the batch query mode. Genetic informations for multiple genes will be displayed on the web page. Users can click the ‘Download’ button to export all the genetic data of their queried genes. The exported file is an excel file with tab-separated value. The excel contains information on: Entrez gene id, gene symbol, band, syndromic autism, GWAS score, CNV score, linkage score, association score, expression score, NGS and other scores of the study, total score through searching by gene symbols or Entrez gene ids. Or it contains: snp id, snp name, Entrez gene id, gene symbol, association fbat number, association case control number, GWAS fbat number, GWAS case ontrol number, result. The file may also contain: PubMed id, year, first author, corresponding author, corresponding author and related genes.

v. The webpages for displaying gene information.

a) On the evidence webpage, we changed the display methods of nucleotide sequence or protein sequence. In the old version, users need to click the button to see the sequences. In the new version, the sequences were automatically displayed 1050 bases or 533 amino acids. For sequences longer than 1050 bases or 533 amino acids, users can use the show/hide button to browse the full sequences. Besides, we changed the genetic information to the phenotypic information.

b) Simultaneously, we have newly added a web page (View Variants) to display genetic information. For CNVs/SVs, in addition to chromosomal coordinates, gain or loss information, we also provide an external link to UCSC browser. For SNVs/InDels, we showed the number of SNVs/InDels in association, GWAS and NGS; at the same time, users can click on the link of SNV ID to see the details of the SNV. For mosaics, we showed chromosomal coordinates and genotype type. The detailed Information of a mosaic variant, includes 3 parts: standard variant information, extended variant information and annotation information. The standard information includes validated method and mutation information. The extended information includes sequencing information. The annotation information is the prediction information using iFish, 12 attributes are displayed for each variant, such as: Probablity, Prediction, SIFT, Phylop, Polyphen2_HDIV, Polyphen2_HVAR, MutationAssessor, GERP_RS, dScore, CpG, Hydropathicity, Polarity. For linkage regions, we showed chromosomal information, marker, LOD score and p value.

Besides, we converted the chromosome coordinate from hg18 to hg19.