TICTAC: Target Illumination Clinical Trial Analytics with Cheminformatics

Abstract

Introduction: Identifying disease-target associations is a pivotal step in drug discovery, offering insights that guide the development and optimization of therapeutic interventions. Clinical trial data serves as a valuable source for inferring these associations. However, issues such as inconsistent data quality and limited interpretability pose significant challenges. To overcome these limitations, an integrated approach is required that consolidates evidence from diverse data sources to support the effective prioritization of biological targets for further research. Methods: We developed a comprehensive data integration and visualization pipeline to infer and evaluate associations between diseases and known and potential drug targets. This pipeline integrates clinical trial data with metada, providing an analytical workflow that enables the exploration of diseases linked to specific drug targets as well as facilitating the discovery of drug targets associated with specific diseases. The pipeline employs robust aggregation techniques to consolidate multivariate evidence from multiple studies, leveraging harmonized datasets to ensure consistency and reliability. Disease-target associations are systematically ranked and filtered using a rational scoring framework that assigns confidence scores derived from aggregated statistical metrics. Results: Our pipeline evaluates disease-target associations by linking protein-coding genes to diseases and incorporates a confidence assessment method based on aggregated evidence. Metrics such as meanRank scores are employed to prioritize associations, enabling researchers to focus on the most promising hypotheses. This systematic approach streamlines the identification and prioritization of biological targets, enhancing hypothesis generation and evidence-based decision-making. Discussion: This innovative pipeline provides a scalable solution for hypothesis generation, scoring, and ranking in drug discovery. As an open-source tool, it is equipped with publicly available datasets and designed for ease of use by researchers. The platform empowers scientists to make data-driven decisions in the prioritization of biological targets, facilitating the discovery of novel therapeutic opportunities.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This work was partially supported by US National Institutes of Health [U24 224370] "Illuminating the Druggable Genome Knowledge Management Center" (IDG KMC).

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study used ONLY openly available human data that were originally located at ClinicalTrials.gov and the derived CTTI AACT database.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Data Availability

All data produced are available online at https://github.com/unmtransinfo/TICTAC, as described in the manuscript, or, available upon reasonable request to the authors.

https://github.com/unmtransinfo/TICTAC

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