DILIsym® Development

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DILIsym® development expands the scope of the software (e.g., extension to other DILI mechanisms) and updates the software to include relevant newly published data. The DILI-sim Initiative approves the particular areas of development, ultimately shaping the focus areas where the DILIsym® modeling software will be able to most immediately support drug development programs.

DILIsym® v6A Development Ongoing

DILIsym® v6A will include more detailed documentation to support optimal DILIsym® use, an enhanced representation of the innate immune response, an initial representation of an adaptive immune response, and additional exemplar compounds.

Development further includes re‑optimization of MITOsym®, the companion software to DILIsym®, based on intracellular compound concentrations.

Documentation

DILIsym® v6A will include an online documentation site which is searchable, contains cross-referencing across different sections, and contains different media (e.g., video tutorials, LaTex equations, network graphs for visualization of sub‑models). This will enable users to access from one location, the multiple resources available to facilitate their understanding and application of DILIsym®. Content will include the previously separate DILIsym® Notes, DILIsym® User Guide, and DILIsym® Input Panel, as well as diagrams previously available in JDesigner, and new How-to Guides for exemplar compounds.

Innate and Adaptive Immune Responses

The representation of innate immunity will include survival/proliferative TNF-α pathways and neutrophils. The representation of adaptive immunity in DILI is a long‑term effort. The initial representation will include antigen presentation and T cell response to an exemplar antigen in the mouse representation. Expanding the innate immune representation improves the biological fidelity of the immune response and will give DILIsym® users greater flexibility in exploring its putative contribution to liver injury. Extending towards the representation of adaptive immune responses consolidates the published record of liver T cell responses to natural and model antigens with available data on DILI and will eventually permit the simulation and exploration of T cell mediated liver injury within DILIsym®.

Additional exemplar compounds

Expanding the exemplar compound representation will give DILIsym® users greater confidence in the exploratory and predictive abilities of the model going forward.

Next Generation DILIsym® Development

Beyond DILIsym® version 6A, model development may add further detail in areas already within the scope of the model (e.g., inflammation associated with fatty liver) and/or may expand the scope into additional areas (e.g., GLDH, more patient populations, cholangiocytes). Future directions will be determined by the availability of data and the priorities of the DILI-sim consortium members.

Companies Supporting DILIsym® Software Development

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