Pharos: Collating protein information to shed light on the druggable genome

Abstract

The 'druggable genome' encompasses several protein families, but only a subset of targets within them have attracted significant research attention and thus have information about them publicly available. The Illuminating the Druggable Genome (IDG) program was initiated in 2014, has the goal of developing experimental techniques and a Knowledge Management Center (KMC) that would collect and organize information about protein targets from four families, representing the most common druggable targets with an emphasis on understudied proteins. Here, we describe two resources developed by the KMC: the Target Central Resource Database (TCRD) which collates many heterogeneous gene/protein datasets and Pharos (https://pharos.nih.gov), a multimodal web interface that presents the data from TCRD. We briefly describe the types and sources of data considered by the KMC and then highlight features of the Pharos interface designed to enable intuitive access to the IDG knowledgebase. The aim of Pharos is to encourage 'serendipitous browsing', whereby related, relevant information is made easily discoverable. We conclude by describing two use cases that highlight the utility of Pharos and TCRD.

Figure 1.

Examples of Pharos UI elements designed to enhance usability and encourage serendipitous discovery. (A) categorized autosuggest functionality available in free text searches. (B) The Table of Contents widget, on a target detail page, that provides the user with an overview of the data types available for the target being viewed and allows direct navigation to individual data types. In addition, the widget supports of all data for the current target and viewing the JSON representation for this target available from the underlying API. (C) A screenshot of the target list view that is obtained either via free text search or by browsing the entire set of targets.

Figure 2.

The use of radar charts to summarize data availability for multiple targets schematically (A) or in interactive detail for a single target (B). The data underlying all radar charts are obtained from the Harmonizome resource (9) and can be downloaded from Pharos for individual targets.

Figure 3.

Harmonograms—heatmaps of the cumulative probability of association between a target and a Harmonizome data source, for two target sets. (A) Kinase targets with a Tclin classification. (B) GPCRs with a Tdark classification. Brighter red indicates more data associated with a target for a given data source and grey represents no data associated with a target in that data source.