Dark Kinase Expression Data Browser

We've developed a browser for the expression data collected by the GTEx consortium and the Human Proteome Map Project with a focus on the relative expression of the dark kinases in context with the entire kinome. This browser displays understudied kinases with especially high expression in the tissues that have been studied by the GTEx and the HPM consortiums. The results can be browsed on the basis of specific kinases or organ/tissue systems.


Coral: Clear and Customizable Visualization of Human Kinome Data

Coral is a user-friendly interactive web application for visualizing both quantitative and qualitative data. Unlike previous tools, Coral can encode data in three features (node color, node size, and branch color), allows three modes of kinome visualization (the traditional kinome tree as well as radial and dynamic-force networks) and generates high-resolution scalable vector graphic files suitable for publication without the need for refinement in graphic editing software. Due to its user-friendly, interactive, and highly customizable design, Coral is broadly applicable to high-throughput studies of the human kinome.

Coral was developed in collaboration with the Phanstiel lab and is available through github and the web.


The Small Molecule Suite: A Set of Tools to Explore Small Molecule Perturbagens

The Small Molecule Suite is a collection of cheminformatics tools that allow researchers to get insight in the selectivity and similarity of compounds and build custom chemical genetics libraries based on desired target coverage and other user-specified criteria. The applications in the suite use state-of-the-art quantitative methods such as target affinity spectrum similarity and phenotypic fingerprint similarity, which are data-driven. The suite updates regularly to keep incorporating the latest published data.

The Small Molecule Suite was developed by the Laboratory of Systems Pharmacology and the Laboratory for Statistical Genomics and Systems Biology. It is freely available on github and the web.


INDRA

INDRA (Integrated Network and Dynamical Reasoning Assembler) is an automated model assembly system, originally developed for molecular systems biology and currently being generalized to other domains. INDRA draws on natural language processing systems and structured databases to collect mechanistic and causal assertions, represents them in a standardized form (INDRA Statements), and assembles them into various modeling formalisms including causal graphs and dynamical models. INDRA also provides knowledge assembly procedures that operate on INDRA Statements and correct certain errors, find and resolve redundancies, infer missing information, filter to a scope of interest and assess belief.


IDG Chemical Tools

The Kinase Chemogenomic Set (KCGS) is a collection of narrow spectrum small molecule kinase inhibitors that is available from the SGC-UNC. The set contains inhibitors with sub-µM biochemical activity on 39 dark kinases. Each inhibitor has been cross-screened on hundreds of human kinases and demonstrates a selectivity index at 1 µM < 0.05 (number of kinases inhibited by 90% divided by the total number of kinases screened). KCGS is available in aliquots of 1 µL of a 10 mM DMSO solution in 96 well plates.

Dark kinase inhibitors that demonstrate IC50 < 1 µM in a live cell NanoBRET assay have been designated as IDG Chemical Tools. A list of the current IDG Chemical Tools can be found here.


IDG Reactome

The Reactome Knowledgebase of Human Biological Pathways and Processes is a curated and peer-reviewed knowledgebase available online as an open access resource that can be freely used and distributed by all members of the biological research community. Reactome extends the classic maps of intermediary metabolism by broadening the scope of reactions to include components of signaling, transport and other processes of cell biology. With tools and techniques such as pathway visualization and enrichment analysis, Reactome can be used to reduce large, complex and noisy genome-scale datasets involving thousands of genes to a manageable set of patterns, from which to draw testable hypotheses relating specific processes, their interplay, and their role in generating disease phenotypes. The Reactome IDG portal is designed to project understudied proteins, including dark kinases, onto the well-known pathway contexts, facilitating to infer potential functional involvement of these proteins within the pathways.

The Reactome was developed by an international multidisciplinary team from OICR, OHSU, EMBL-EBI, and NYULMC.


Clinical Kinase Index

The Clinical Kinase Index (CKI) is an interactive App developed by the Schürer lab to search browse and visualize the clinical relevance of kinases for solid tumors based gene expression data from the TCGA integrated with survival-, tumor (TNM)-, pathological-, and histological staging data, and various kinase annotations, including target development level, and phylogenetic and functional classifications. This tool has been published in Cell Reports Medicine.


Preview Tools and Applications



Kinase Inhibitor Cell Viability Predictions - kipred Server

The kinase inhibitor cell viability prediction server is a tool that allows any user with an RNAseq data set to make cell viability predictions for a set of about 230 kinase inhibitors. These inhibitors were previously characterized using a mass spectroscopy kinobead assay. Using this data, cell viability results associated with each compound from PRISM and other multiomic data from the CCLE, we have developed a model that uses RNAseq data to make custom predictions for this set of kinase inhibitors. To make it easier for potential users to access this tool, we have also used the pre-processed RNAseq data available through ARCHS4 to enable any human GEO data sample to processed without any need for the user to upload their data. The ARCHS submission was made possible through a collaboration with Alexander Lachmann and Avi Ma'ayan.