# TICTAC: target illumination clinical trial analytics with cheminformatics

**Authors:** Jeremiah I. Abok, Jeremy S. Edwards, Jeremy J. Yang

PMC · DOI: 10.3389/fbinf.2025.1579865 · 2025-06-09

## TL;DR

This paper introduces TICTAC, a tool that combines clinical trial data and cheminformatics to identify and prioritize disease-target associations for drug discovery.

## Contribution

The novel contribution is a data integration pipeline that systematically ranks disease-target associations using aggregated evidence and statistical metrics.

## Key findings

- The pipeline integrates clinical trial data with standardized metadata to prioritize biological targets.
- A scoring framework assigns confidence scores to disease-target associations using meanRank metrics.
- The open-source tool enables scalable hypothesis generation and data-driven decision-making in drug discovery.

## Abstract

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.

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 standardized metadata, 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.

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.

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.

## Full-text entities

- **Genes:** MC4R (melanocortin 4 receptor) [NCBI Gene 4160] {aka BMIQ20}, BDKRB2 (bradykinin receptor B2) [NCBI Gene 624] {aka B2R, BK-2, BK2, BKR2, BRB2}, ADK (adenosine kinase) [NCBI Gene 132] {aka AK}, PGR (progesterone receptor) [NCBI Gene 5241] {aka NR3C3, PR}, MAP4K4 (mitogen-activated protein kinase kinase kinase kinase 4) [NCBI Gene 9448] {aka FLH21957, HEL-S-31, HGK, MEKKK4, NIK}, SLC5A2 (solute carrier family 5 member 2) [NCBI Gene 6524] {aka SGLT2}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, COQ8A (coenzyme Q8A) [NCBI Gene 56997] {aka ADCK3, ARCA2, CABC1, COQ10D4, COQ8, SCAR9}, RAC1 (Rac family small GTPase 1) [NCBI Gene 5879] {aka MIG5, MRD48, Rac-1, TC-25, p21-Rac1}, CISD2 (CDGSH iron sulfur domain 2) [NCBI Gene 493856] {aka ERIS, Miner1, NAF-1, WFS2, ZCD2}, UGT1A10 (UDP glucuronosyltransferase family 1 member A10) [NCBI Gene 54575] {aka UGT-1J, UGT1-10, UGT1.10, UGT1J}
- **Diseases:** lung cancer (MESH:D008175), insulin resistance (MESH:D007333), Type2 diabetes (MESH:D003920), CUIs (MESH:C566733), COVID-19 (MESH:D000086382), type 2 diabetes (MESH:D003924), Disease (MESH:D004194), heart failure (MESH:D006333), TICTAC (MESH:D002249), metabolic disorders (MESH:D008659)
- **Chemicals:** Sorafenib (MESH:D000077157), 5-Fluorouracil (MESH:D005472), glucose (MESH:D005947), Abemaciclib (MESH:C000590451), fatty acid (MESH:D005227), oxygen (MESH:D010100), aspirin (MESH:D001241), Carboplatin (MESH:D016190), Dasatinib (MESH:D000069439), AACT (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12183303/full.md

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Source: https://tomesphere.com/paper/PMC12183303