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
Documentation Guide
A compact guide to the walkthrough, method primers, and rendered HTML notes.
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