INDRA integrates multiple text-mining systems and pathway databases to automatically extract mechanistic knowledge from the biomedical literature and through a process of knowledge assembly, build executable models and causal networks. Based on profiling and perturbational data, these models can be contextualized to be cell-type specific and used to explain experimental observations or to make predictions.
In the context of the
DARPA Panacea program,
INDRA team at the
Laboratory of Systems Pharmacology, Harvard Medical School
is working on understanding the regulation of pain and inflammation with the
goal of finding new therapeutics using INDRA.
We used INDRA to assemble all mechanisms that 65 ion-channels that are particularly important for nociception are involved in.
Each ion-channel’s interactions can be browsed as networks at
And the literature evidence can be inspected on the pages linked to below. These
pages alsow support expert curation of statements which are fed back to INDRA
to improve the models (see curation tutorial
The ion-channel inhibitor search is an application that allows selecting some
ion-channels as “desirable” drug targets and others as “undesirable” drug targets.
The application then searches all INDRA Statements in the ion-channel knowledge
base, combined with the
Small Molecule Suite / Target Affintiy Spectrum
data to find regulators (drugs or other entities that may be relevant) with
the desired properties.
The ion-channel inhibitor search is available
EMMAA (Ecosystem of Machine-maintained Models with Automated Analysis) makes available a set of computational models that are kept up-to-date using automated machine reading, knowledge-assembly, and model generation, integrating new discoveries immediately as they become available.
The EMMAA model representing pain mechanisms can be found
Using transcriptional data collected in the
of immune cells and neurons following injury, we are building
cell-type specific models of how immune cells and pain sensing neurons interact.
There are several applications built on top of INDRA that that are generally applicable to biomedical research and can therefore also be used to study pain mechanisms.
INDRA database: The INDRA database website provides a search interface to find INDRA Statements assembled from the biomedical literature, browse their supporting evidence, and curate any errors. Az example search relevant to Panacea is Object: SCN10A to find entities that regulate the Nav 1.8 ion channel.
INDRA network search: The INDRA network search allows finding causal paths, shared regulators, and common targets between two entities. An example search relevant to Panacea is Subject: bradykinin, Object: PKC (see
Dialogue.bio: The dialogue.bio website allows launching dedicated human-machine dialogue sessions where you can upload your data (e.g., DE gene lists or gene expression profiles), discuss relevant mechanisms, and build model hypotheses using simple English dialogue. For instance, you could try the following series of questions: “what is Nav1.8?”, “what does it regulate?”, “which of those are transcription factors?”.
This project is funded under the DARPA Panacea program (HR00111920022).