1. What is the HisgAtlas?

HisgAtlas is the first database that stores a list of immunosuppression genes collected by literature mining and manual curation. 995 human immunosuppression genes and 260 associated diseases are collected in this database.

2. How to search the database of HisgAtlas?

Users may search HisgAtlas in two ways.

Users can input a gene name in the "Gene Name" search box and a drop-down menu will provide auto-completed genes stored in the database. Selecting one of them and clicking the "Search" button will lead to the queried results containing a table showing the immunosuppression genes, their associated diseases as well as the supporting evidence. All current query terms will be deleted if users click the "Reset" button.

Users can input a disease name in the "Disease Term" search box, and a drop-down menu will provide auto-completed diseases stored in the database. Selecting one of them and clicking the "Search" button will lead to the queried results containing a table showing the immunosuppression associated diseases, their effector genes as well as the supporting literature evidence.

Clicking on the hyperlink of the gene symbol in the "Gene" column will lead to the annotation information of the gene and the cross-references to external databases (i.e. Ensembl, NCBI Gene, UniProtKB, neXtProt and Antibodypedia).

When the user clicks the small triangle in the head of each column in the table, the corresponding results in the table will be resorted in ascending/descending order by the column. And the user can also input words or select a term in the drop list in the text box to filter the listed genes, diseases from the results by sub-string match.

When the user clicks the number of the evidence abstracts or sentences, a table containing gene, disease, the PubMed ID, the evidence sentence and the manual validation information will be displayed. The user can click on the sentence to see the original abstract in which the keywords, gene and disease names, are highlighted.

3. How to browse and download data in HisgAtlas？

The complete list of human immunosuppression genes and immunosuppression associated diseases can be browsed by clicking the ‘Browse & Download" button in the navigation bar. All the information for immunosuppression genes and their supporting literature evidence can be downloaded for further analysis.

In HisgAtlas 1.0, we extracted two lists of genes defined as "immune checkpoint" and "membrane protein" from their evidence sentences. These two buttons allow users to quickly browse these genes. We believe this is useful for laboratory technicians and pharmaceutical researchers looking for further study.

4. Where is the human immunosuppression gene from?

Our text mining is based on the immunosuppression abstracts from PubMed. Self-developed ontology-based bio-entity recognizer was used to perform bio-entity recognition and extraction from these abstracts for human immunosuppression gene candidates. Our recognition tool has the precision, recall and F-measure of 0.810, 0.883 and 0.845 against the CRAFT corpus for gene/protein recognition based on Protein Ontology (PR), which is comparable to current state-of-the-art biomedical annotation systems like BeCAS.

Three steps were taken to compile a list of human immunosuppression genes with their related diseases and evidence. First, 120,176 PubMed abstracts and 180,063 sentences related to immunosuppression were collected with the listing keywords: ‘immunosuppression’, ‘tumor immune escape’, ‘inhibit T cell’, ‘immunotolerance’, ‘immune checkpoint’, ‘immune deviation’, ‘peripheral tolerance’, ‘central tolerance’, ‘allograft tolerance’, ‘oral tolerance’, ‘split tolerance’, ‘self-tolerance’, ‘natural tolerance’, ‘acquired tolerance’ and their lexical variants. Second, 3634 human genes considered as candidate immunosuppression genes were recognized and extracted from these sentences based on Protein Ontology which co-occurred with the immunosuppression keywords at the single-sentence level. Third, strict three-round manual curation was performed on these candidates by our experts, finally generating 995 high confidence human immunosuppression genes.

Disease terms were extracted from abstracts based on Human Disease Ontology (DO). Associations between immunosuppression genes/proteins and human disease terms were extracted based on sentence-level co-occurrence. Furthermore, whether a gene is an immune checkpoint has been recognized and marked. All extracted immunosuppression genes/proteins, human disease terms and evidence abstracts were loaded into MySQL database.

5. Where is the human immunosuppression gene related drug from?

We extracted 410 drugs under ‘Immunoglobulins’, ‘Immunoproteins’, ‘Immunosuppressive Agents’, ‘Antineoplastic and Immunomodulating Agents’ categories from Drugbank, then we mapped these drugs to immunosuppression genes using disease-drug relations extracted from the XML format of DrugBank. Manual validatation were perform on these mappings to ensure data quality. Finally, we obtained 270 immunosuppression gene related drugs.

6. What is the data quality control in HisgAtlas？

To ensure the data quality, three rounds of strict manual curation were taken for the identification of immunosuppression genes. First, all candidate immunosuppression genes and supporting evidence were checked by two experienced researchers independently. Second, these selected evidence were submitted to an internal review, in which all immunosuppression gene names were manually reviewed one by one by a reviewer team consisting of three experts. Third, all co-authors were asked to randomly check immunosuppression genes from our website to make sure that all genes stored in our database are high confidence immunosuppression genes. Finally, we obtained 995 genes and 260 associated diseases. All the evidence sentences that have been manually curated are regarded as validated evidence and included on the top of each immunosuppression gene page.

7. What is "Manual Curation" by community?

The community can contribute to the manual curation of HisgAtlas by clicking Yes/No in the ‘Manual Curation’ column or input their comments on the evidence phrase by clicking "Comments" button.

To avoid the attack by robot, the login is necessary. Users can log in by clicking here

We will monitor and validate community curation feedback before inclusion in the database.

Here we offer a trial account for the curation function (Account: "test@test.com", Password: "test").

Note: All the other functions of HisgAtlas including data retrieval, browsing and downloading do not require any login or registration.

8. Can users provide their immunosuppression genes to HisgAltas?

Yes, we added "Feedback" feature to our website, with which the user can submit new genes to our database manually, the database will be updated periodically in the future.

Users can also contact us for any questions or potential collaborations.

9. What does "Gene Name" mean?

Gene names mean formal gene symbols and their synonyms provided by RefSeq.

10. What does "Disease Term" mean?

Disease terms mean standardized disease names and their common synonyms provided by Human Disease Ontology.

11. What does "Immune Checkpoint" mean?

Immune checkpoints refer to a plethora of inhibitory pathways hardwired into the immune system that are crucial for maintaining self-tolerance and modulating the duration and amplitude of physiological immune responses in peripheral tissues in order to minimize collateral tissue damage.

12. What does "Membrane Protein" mean?

Membrane proteins mean all the proteins and protein complexes embedded in or attached to a biological lipid bilayer, which are annotated with the term GO:0016020 provided by Gene Ontology Annotation (UniProt-GOA) Database.