KinMap: a web-based tool for interactive navigation through human kinome data

Abstract

Background: Annotations of the phylogenetic tree of the human kinome is an intuitive way to visualize compound profiling data, structural features of kinases or functional relationships within this important class of proteins. The increasing volume and complexity of kinase-related data underlines the need for a tool that enables complex queries pertaining to kinase disease involvement and potential therapeutic uses of kinase inhibitors.

Results: Here, we present KinMap, a user-friendly online tool that facilitates the interactive navigation through kinase knowledge by linking biochemical, structural, and disease association data to the human kinome tree. To this end, preprocessed data from freely-available sources, such as ChEMBL, the Protein Data Bank, and the Center for Therapeutic Target Validation platform are integrated into KinMap and can easily be complemented by proprietary data. The value of KinMap will be exemplarily demonstrated for uncovering new therapeutic indications of known kinase inhibitors and for prioritizing kinases for drug development efforts.

Conclusion: KinMap represents a new generation of kinome tree viewers which facilitates interactive exploration of the human kinome. KinMap enables generation of high-quality annotated images of the human kinome tree as well as exchange of kinome-related data in scientific communications. Furthermore, KinMap supports multiple input and output formats and recognizes alternative kinase names and links them to a unified naming scheme, which makes it a useful tool across different disciplines and applications. A web-service of KinMap is freely available at http://www.kinhub.org/kinmap/ .

Keywords: Human kinome tree; Images; Interactive annotation; Protein kinases.

Fig. 1

The KinMap web interface. a Summary of the key features. b Navigation panel which allows linking kinome related data sources, e.g. non-small cell lung carcinoma from CTTV (green triangles). c Preview of the built-in spreadsheet editor showing inhibition profile of erlotinib (red circles on the tree) [4]; auto-complete functions (blue rectangles) facilitate kinase selection and style modification. Annotation sizes can be automatically rescaled based on bioactivity data (red rectangles) or other input values in the spreadsheet. d Kinase name suggestions in case of incomplete or ambiguous names in the input. e Supported output formats CSV: comma-separated values; PNG: Portable Network Graphics; SVG: Scalable Vector Graphics; XML: extensible markup language; KMAP: native KinMap format. A box showing detailed information for the ABL1 kinase illustrates the interactive view mode

Fig. 2

Examples of kinome tree annotation created by KinMap. a Inhibition profiles of two approved drugs sorafenib (orange circles) and sunitinib (creme circles) [4], and kinases linked to thyroid carcinoma (blue squares) and colonic neoplasm (red squares) as extracted from the CTTV platform [14]. b Availability of structural and bioactivity data for the human kinome; red circles: number of structures per kinase in the PDB [11]; blue circles: number of activity measurements for the respective kinase in ChEMBL [12]; green triangles: key targets of clinically approved kinase inhibitors [12]