GtoImmuPdb: technical update November 2016

During October we have made the first alpha-release (v1.0) of the Guide to IMMUNOPHARMACOLOGY. This blog post summarises some of the main features of the release and work on the documentation.

This first release marks an important step towards the public deployment of the first beta-release of GtoImmuPdb, scheduled for Spring 2017. We expect to make further alpha-releases over the next few months, as additional features are added.

An early synopsis of the project can be found in this blog post. Previous technical blogs are available for February, May, August & September 2016.

Development Progress

Alpha-Release v1.0

The portal has its own unique branding (header bar, logo and colour scheme) to distinguish it, but retains many of the layout features from the main GtoPdb site. This consistency should help users already familiar with GtoPdb to orientate themselves with the new GtoImmuPdb.

Screenshot of the GtoImmuPdb Portal, alpha-release v1.0

The portal provides a starting-point for accessing data in GtoImmuPdb, tailored to the requirements of users with a specific interest in immunopharmacology. Browsing by target, process and cell-type have been implemented in the alpha_v1.0 release. Ligands can be browsed, but there isn’t yet a immuno specific view for the results.

The portal and other pages with the GtoImmuPdb view toggled on will display a specific Guide to IMMUNOPHARMACOLOGY header and menu-bar. A consistent feature on the GtoImmuPdb pages is a ‘toggle’ button that enables the user to switch out to the standard GtoPdb view (and back).

Family page on GtoImmuPdb, showing new header and toggle button (a key feature of GtoImmuPdb)

Alpha-Release v1.0 Documentation

The main area of development over October 2016 has been to prepare the documentation for the alpha-release. These provide an explanation of the features included, how data was obtained and curated and how to use the site. Detailed release notes have been prepared, which will be incrementally added to or appended to on subsequent releases. They cover the following main sections:

• GtoImmuPdb portal
• Receptor Family pages
• Family Pages
• Detailed Target pages
• Immuno Process Association List pages
• Immuno Cell Type Association List pages
• Search
• Database Development

Documentation has also been prepared that gives details on how the data for both the process and cell type associations has been obtained. This includes a detailed spreadsheet on the full GO annotations, obtained via UniProt that form the basis of the immuno process associations.

We have also prepared a tutorial document that is a guide to navigating from the new portal, to access GtoImmuPdb data and understand the new GtoImmuPdb pages.

Alpha-Release v1.0 Data

GtoImmPdb uses the same underlying database as GtoPdb. This is has been extended to include and integrate GtoImmPdb data. The primary data-types of interest to GtoPdb, that have been addresses so far, are processes and cell-types. The database schema has been extended to accommodate these data-types and to associate them with targets in the database.

Immuno Process Data

GtoImmuPdb has defined its own set of top-level immunological process categories against which targets in the database can be annotated and which form the basis of organising, navigating and searching for immunological processes and associations.

These categories are:

• Immune system development and differentiation
• Proliferation and cell death
• Production of signals and mediators
• Regulation and responses to signals
• Migration and chemotaxis
• Cell-mediated immunity
• Inflammation

We have associated sets of Gene Ontology (GO) terms with each of these categories. This enables us to auto-curate targets annotated to any of those terms (or their children) by GO into our top-level immunological categories. GO data is obtained via an OBO file (http://purl.obolibrary.org/obo/go.obo) for the ontology, which is edited to restrict it to immuno-specific terms. We auto-curate targets to the top-level process terms by using GO annotation information from UniProt. Through UniProt, targets were selected that were annotated to the subset of GO terms and also cross-referenced in GtoPdb. This gave a total of 1,855 annotation to 401 targets.

The table below summaries the unique targets (UniProt) annotated under each category

GtoImmPdb ‘High-Level’ Process	Distinct UniProt
Immune System Development and Differentiation	124
Proliferation and Cell Death	33
Production of Signals and Mediators	74
Regulation and Responses to Signals	355
Migration and Chemotaxis	81
Cell-Mediated Immunity	99
Inflammation	261

Provision has been made in the database schema to capture curator comments against process information and annotations and the design is fully-adaptable to future changes.

Cell Type Data

The Cell Ontology provides the formalised vocabulary against which we annotated target to cell type associations. GtoImmuPdb has defined its own set of top-level immunological cell type categories against which targets in the database can be annotated and which form the basis of organising, navigating and searching for immunological cell types and associations.

These categories are:

• pro-B-lymphocytes, B lymphocytes & Plasma cells
• T lymphocytes (alpha-beta type) and their immediate progenitors
• T lymphocytes (gamma-delta type) and their immediate progenitors
• Natural Killer (NK) cells
• Polymorphonuclear leukocytes (neutrophils, eosinophils, basophils)
• Mononuclear leukocytes (syn: monocytes) (macrophages, dendritic cells, Kupffer cells)
• Mast Cells
• Innate Lymphoid Cell (added November 2016)

We have assigned one or more Cell Ontology terms to each of these categories. The assigned CO terms represents the highest level parent term(s) within the ontology for that category. For the purposes of annotation, it is these CO terms and their children that can be used when annotating a target to a given category. The exception is innate lymphoid cells which at present are not defined and included in the Cell Ontology.

Other Developments & Next Steps

Fixes have been made to out submission tool to include the ability to add/remove cell type categories and to add definitions/description of them.

Our focus in the next month is to develop the ligand browse landing pages (accessed via Ligand panel on the portal home), and add in icons to highlight immuno-flagged ligands throughout the main GtoPdb site.

We also want to develop the menu-bar navigation for GtoImmuPdb, as this will be important for the beta-release.

This project is supported by a 3-year grant awarded to Professor Jamie Davies at the University of Edinburgh by the Wellcome Trust (WT).