Analysis Walkthrough
- Start with screening evidence: use public ROR gamma qHTS and counterscreen-style data as the HTS layer for upstream Th17 biology.
- Filter artifacts: combine primary activity, counterscreen behavior, selectivity, and artifact flags into a screen QC score.
- Add disease relevance: overlay psoriasis transcriptomic evidence so screening hits are not interpreted outside disease context.
- Validate at protein level: add proteomics support and explicitly flag RNA/protein discordance.
- Localize the biology: use single-cell context to distinguish T-cell, keratinocyte, myeloid, or broad inflammatory signals.
- Add protein and structure context: treat protein model and structure features as interpretive support, not proof of mechanism.
- Make the decision auditable: generate a transparent ranking and evidence cards with limitations and next validation experiments.
Project Notes And Primers
Walkthrough
Read the analysis logic from screening evidence through ranked follow-up decisions.
Project Plan
Review the workflow design, scoring model, and planned extensions.
Scientific Review
See the critical review notes, biological interpretation, and next-version roadmap.
Primers
Short background notes for HTS, psoriasis biology, proteomics, protein models, structure prediction, evidence summaries, and FAIR workflows.
HTS · IL-17 · Proteomics · Protein models · Structure · Evidence summaries · FAIR/AWS
Candidate Ranking
| Rank | Gene | Protein | Score | Screen QC | Cell Context | Limitations |
|---|---|---|---|---|---|---|
| 1 | IL17A | Interleukin 17A | 0.806 | moderate_screen_support | T cells | No major limitation flagged beyond compact public example-data scope. |
| 2 | RORC | RAR-related orphan receptor gamma | 0.774 | strong_screen_support | T cells | weak protein-level support; pathway-proximal qHTS, not direct IL-17 peptide screen |
| 3 | IL23R | Interleukin 23 receptor | 0.683 | moderate_screen_support | T cells | No major limitation flagged beyond compact public example-data scope. |
| 4 | STAT3 | Signal transducer and activator of transcription 3 | 0.563 | weak_screen_support | Keratinocytes and immune cells | weak protein-level support |
| 5 | TNF | Tumor necrosis factor | 0.505 | artifact_risk | Myeloid cells and T cells | counterscreen artifact risk |
Score Breakdown
Screening vs Disease Evidence
Grounded Evidence Cards
IL17A
Summary: IL17A ranks #1 with a transparent score of 0.806. The candidate combines moderate_screen_support screening evidence, disease score 0.95, proteomics score 0.87, and T cells cell-type context. This is a hypothesis-generating prioritization result, not proof of therapeutic efficacy.
Limitations: No major limitation flagged beyond compact public example-data scope.
Next validation: Validate pathway modulation in a psoriasis-relevant keratinocyte/immune co-culture assay with orthogonal protein readouts.
PubChem AID2604/AID2546; GSE54456; PXD021673; GSE162183
RORC
Summary: RORC ranks #2 with a transparent score of 0.774. The candidate combines strong_screen_support screening evidence, disease score 0.78, proteomics score 0.48, and T cells cell-type context. This is a hypothesis-generating prioritization result, not proof of therapeutic efficacy.
Limitations: weak protein-level support; pathway-proximal qHTS, not direct IL-17 peptide screen
Next validation: Validate pathway modulation in a psoriasis-relevant keratinocyte/immune co-culture assay with orthogonal protein readouts.
PubChem AID2604/AID2546; GSE54456; PXD021673; GSE162183
IL23R
Summary: IL23R ranks #3 with a transparent score of 0.683. The candidate combines moderate_screen_support screening evidence, disease score 0.86, proteomics score 0.62, and T cells cell-type context. This is a hypothesis-generating prioritization result, not proof of therapeutic efficacy.
Limitations: No major limitation flagged beyond compact public example-data scope.
Next validation: Validate pathway modulation in a psoriasis-relevant keratinocyte/immune co-culture assay with orthogonal protein readouts.
PubChem AID2604/AID2546; GSE54456; PXD021673; GSE162183
STAT3
Summary: STAT3 ranks #4 with a transparent score of 0.563. The candidate combines weak_screen_support screening evidence, disease score 0.64, proteomics score 0.45, and Keratinocytes and immune cells cell-type context. This is a hypothesis-generating prioritization result, not proof of therapeutic efficacy.
Limitations: weak protein-level support
Next validation: Test specificity of pathway modulation and separate broad signaling effects from disease-selective biology.
PubChem AID2604/AID2546; GSE54456; PXD021673; GSE162183
TNF
Summary: TNF ranks #5 with a transparent score of 0.505. The candidate combines artifact_risk screening evidence, disease score 0.73, proteomics score 0.70, and Myeloid cells and T cells cell-type context. This is a hypothesis-generating prioritization result, not proof of therapeutic efficacy.
Limitations: counterscreen artifact risk
Next validation: Run focused counterscreens to distinguish broad inflammation from specific IL-17 pathway modulation.
PubChem AID2604/AID2546; GSE54456; PXD021673; GSE162183