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2-Tier 3-Level Service
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“2-Tier 3-Level” Service Strategy Maximizes Capacity and Impact at CPDM@UMB

A graphic explaining the structure of the CDPM. It features two tiers of animal models, the first being drosophila and zebra fish precision disease models, and the second being mouse precision disease models. The three tiers are model generation, variant function and mechanism investigation, and therapeutic development.

CPDM@UMB’s innovative “2-Tier 3-Level” strategy maximizes precision modeling efficiency, meets diverse user needs, and supports translational research (Fig. 2). This approach integrates Drosophila, zebrafish, and mouse models into a streamlined framework for rapid, large-scale variant analysis with rigorous validation and preclinical relevance.

Tier 1: Functional Studies & Precision Models (Drosophila & Zebrafish)

  • Level 1: Generate precision models using Drosophila and zebrafish.
  • Level 2: Conduct phenotypic and multi-omics analyses to uncover disease mechanisms.
  • Level 3: Develop and test mechanism-based therapeutics.

Tier 1 enables rapid, cost-effective analysis of large numbers of community-nominated variants, accelerating disease mechanism discovery and treatment development.

Tier 2: Validation & Preclinical Studies (Mouse Models)

  • Level 1: Generate precision models using CRISPR knock-in mouse models.
  • Level 2: Perform phenotypic and omics analyses to study mechanisms.
  • Level 3: Develop and test mechanism-based therapeutics.

Tier 2 builds on Tier 1 findings, advancing them to mouse models for rigorous validation and preclinical testing, ensuring translational relevance and clinical impact.

Overall Workflow of the “2-Tier 3-Level” Service Strategy at CPDM@UMB

A complex flow chart showcasing the workflow of the CPDM.

Since 2019, CPDM@UMB has refined its precision disease modeling service into a streamlined 15-step “2-Tier 3-Level” workflow to maximize efficiency and impact. This approach supports high-throughput precision disease modeling and translational research to address the diverse needs of the biomedical community.

Steps 1–4: Variant Nomination, Prioritization, and Service Proposal

1. Variant Nomination: Submissions from clinicians, geneticists, and consortia through outreach and a submission form on our website.
2. Evaluation: The Preclinical Section assesses clinical significance (e.g., allele frequency, genotype-phenotype correlation), while the Bioinformatics Section evaluates modeling feasibility (e.g., gene homology, expression).
3. Priority Report: A combined “Variant Feasibility and Priority Report” is submitted to the Coordination Section for review.
4. Service Proposal: If approved, a “Tier 1 Precision Modeling Service Proposal” is sent to the user for feedback, which finalizes the request and allows the Disease Modeling Unit (DMU) to proceed with Tier 1 Level 1 (T1L1) service.

Steps 5–9: Tier 1 Precision Modeling Services

5. Model Generation: The DMU creates Tier 1 models using Drosophila or zebrafish.
6. Phenotypic Analysis: The DMU collaborates with the Preclinical Section for phenotypic assays (T1L2) and with the Bioinformatics Section for multi-omics studies if needed.
7. Therapeutic Testing: The DMU and Preclinical Section test mechanism-based therapies (T1L3).
8. Report Preparation: The DMU compiles model generation, phenotypic analysis, and treatment development reports.
9. Model Transfer: Models and reports are transferred to the Service & Resource Section for distribution and user feedback.

Steps 10–15: Tier 2 Precision Modeling Services

10. Tier 2 Proposal: If Tier 1 results are promising, the DMU prepares a Tier 2 proposal for mouse models, which is reviewed by the Coordination Section and Steering Committee.
11. Mouse Model Generation: The DMU generates Tier 2 mouse models.
12. Phenotypic and Multi-Omics Studies: The DMU conducts phenotypic analysis (T2L2) and multi-omics studies if needed.
13. Therapeutic Testing: The DMU and Preclinical Section test therapies (T2L3).
14. Report Preparation: The DMU compiles reports on model generation, phenotypic analysis, and therapy testing.
15. Model Transfer: Models and reports are managed and distributed by the Service & Resource Section.

This structured 15-step workflow ensures a flexible, efficient pipeline for precision disease modeling, mechanism discovery, and therapy development, positioning CPDM@UMB as a leader in translational research and precision medicine.

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