Euretos has developed in silico methodologies for Indication Expansion: the identification of (alternative) indications for a known target. We perform an in silico perturbation analysis to identify proteins that can correct the dysregulation profile associated with the disease. As part of this procedure, Euretos continuously develops, maintains and expands thousands of molecular disease models as new data becomes available.
High Level Approach
Conceptually, our approach consists of two steps. In the first step, we construct an in silico molecular perturbation model for target modulation (inhibition or stimulation), based on experimental data from the customer, relations in our platform and public data on perturbations such as the Connectivity Map of the Broad Institute. This model aims to quantify the functional consequences of the target modulation in a cell-type dependent manner.
In the second step, we will use the target perturbation model to evaluate the downstream consequences of target modulation in thousands of molecular disease model that have been compiled by Euretos.
A molecular disease model identifies for a specific disease the dysregulated genes, proteins and pathways as well as the underlying cell types and interactions between cell types that are dysregulated. Perturbation of the target using the established mechanism of action is evaluated in each molecular disease model to predict efficacy of target modulation for each indication. The different indications are ranked using a score that quantifies to what extent target modulation is predicted to correct the dysregulation associated with each indication.
For indication expansion, we use perturbation analysis to identify which disease indications are most closely associated with the target of interest.
As a result of the process, we will provide a list of indications ranked using our target-indication score. It builds the case for several indication candidates, elaborates on the molecular drivers for each of the candidates and on the various evaluation criteria.
For a number of selected indications, we will provide a description of the perturbation and disease model, as well as the evidence supporting the indication ranking in a report in the form of a research paper. The report will contain references and links to publicly available knowledge and data supporting the premise of the indication candidate.
Furthermore, the customer will be able to review the target/indications with the gene disease page and the gene detail page in the Euretos AI platform for a 1-month period