CytoSolve® Enables Peer-Reviewed, Evidence-Traceable Systems Architecture of Human Knee Osteoarthritis with UHN Arthritis Program

Partner Description

University Health Network (UHN) – Arthritis Program, Division of Orthopedics
The UHN Arthritis Program is a clinically integrated research group within the Division of Orthopedics, focused on understanding musculoskeletal disease mechanisms and advancing translational strategies for conditions such as knee osteoarthritis.

Challenge

Human knee osteoarthritis (OA) is a multi-tissue, multi-cellular disease involving cartilage, synovium, subchondral bone, meniscus, infrapatellar fat pad, osteophytes, immune components, and pain pathways. The underlying biology is distributed across thousands of publications, each capturing only a narrow mechanistic slice of the disease.

Prior to this collaboration, OA researchers faced three persistent barriers:

  • Scale and complexity: The breadth of interacting tissues, cell types, and molecular mechanisms made it difficult to construct a unified, mechanistic understanding of human knee osteoarthritis.
  • Evidence fragmentation: Thousands of peer-reviewed studies contained valuable mechanistic data, but these findings were dispersed and difficult to synthesize systematically.
  • Limited traceability: Existing pathway diagrams rarely allowed direct linkage from specific molecular interactions back to originating experimental evidence, limiting reproducibility, transparency, and scientific debate.
A peer-review-ready architecture was required—one capable of integrating OA biology across scales while preserving explicit evidence provenance.

How CytoSolve® Helped

CytoSolve® partnered with UHN’s Arthritis Program to build a multi-scale molecular systems architecture of human knee osteoarthritis using a supervised bioinformatics workflow designed for rigor, transparency, and peer-review validation.

The process began with large-scale literature curation. Using PubMed as the primary source (search through June 2017), an initial corpus of 20,231 publications was systematically screened and refined to 5,243 studies using a PRISMA-guided workflow. Only studies meeting strict inclusion criteria were used to construct the architecture.

CytoSolve® implemented a layered, navigable “3D” systems design, enabling structured traversal of OA biology:

  • Layer 1: Knee anatomy and tissue compartments.
  • Layer 2: Tissue-specific cell types (e.g., chondrocytes within cartilage).
  • Layer 3 to n: Molecular ensembles and individual biochemical interactions.
  • Final layer: Direct, clickable linkage to the peer-reviewed paper supporting each reaction.
To ensure scientific validity, CytoSolve® applied rigorous extraction and representation rules. Molecular interactions were preferentially extracted from figures and Results sections, restricted to human OA knee cells (not normal tissue), prioritized human data when multiple species were reported, and avoided secondary reliance on cited external studies. Interaction types were encoded using standardized graphical notation, distinguishing direct molecular binding from inferred expression changes or indirect evidence.

The architecture was further designed to support community feedback and referee-style updates, enabling ongoing peer-review-like curation and long-term scientific relevance.

Key Benefits Realized

  • Peer-review-ready, multi-scale systems architecture spanning tissue → cell type → molecular reaction layers.
  • Explicit evidence traceability, linking each molecular interaction to its originating peer-reviewed study.
  • Quality-controlled mechanistic extraction, reducing propagation of unsupported or ambiguous claims.
  • Actionable framework supporting mechanistic discovery and therapeutic target exploration in knee osteoarthritis.
  • Reusable educational and research scaffold grounded in curated, navigable human osteoarthritis biology.

Outcome

The UHN–CytoSolve® collaboration produced one of the most comprehensive, evidence-linked molecular systems architectures of human knee osteoarthritis to date. By converting a vast and fragmented literature into a structured, explorable, and peer-review-validated resource, CytoSolve® enabled direct traversal from knee anatomy to cell-specific molecular mechanisms with transparent access to supporting evidence. This durable platform now supports mechanistic discovery, translational research, and education in knee osteoarthritis, demonstrating CytoSolve®’s capability to deliver peer-review-grade systems biology infrastructure for complex human diseases.