Our multidisciplinary team has initiated the development of a novel Translator Reasoning Tool—
Reasoning Over Biomedical Objects linked in Knowledge-Oriented Pathways
(ROBOKOP)—to address, in a fully automated way, user queries that can be answered by
concurrent reasoning across Knowledge Sources (KSs) by means of a Knowledge Graph (KG).
Our proof-of-concept (POC) product, PROTOCOP, represents a generalizable solution for
reasoning across KSs to identify answers to clinical and translational research questions such as
establishing data-supported Clinical Outcomes Pathways (COPs) of drugs or pathways explaining
disease-disease interactions. PROTOCOP incorporates several KSs identified by the Translator
project (e.g., chem2bio2rdf, Biolink, Pharos), as well as additional KSs that may be of value to
the broader Translator program such as Chemotext (chemotext.mml.unc.edu), which is a publiclyavailable
webserver that mines the published literature in PubMed in the form of Medical Subject
Headings (MeSH) terms. PROTOCOP has successfully identified solutions to the initial two
translational query types: (1) genetic conditions that protect against disease; and (2) COPs for
drug-condition pairs. Over the 10-month project period, we will refine and evaluate our approach
as we move from PROTOCOP to ROBOKOP and embed it in fully operational and user-friendly
software. We will develop automated approaches to identify high-scoring connected subgraphs
that translate into well-reasoned, data-supported, biological pathways that explain drug action
and disease mechanisms and that may help elucidate new drug targets. In addition, we will
expand the set of allowable queries to include those that rely on longitudinal clinical data and
time- and geospatial-dependent socio-environmental exposures data. We expect that once
developed, ROBOKOP will enable novel, testable hypothesis generation for a number of
biomedical challenges such as drug repurposing, detection of disease comorbidities, mechanistic
interpretation of disease phenotypes in terms of underlying endotypes, and others.