First-time user guide
OpenAntigens builds structure-aware antigen-design reports for human cell-surface and secreted protein targets. Use this guide to search the portal, interpret report sections, prioritize constructs, and export sequences for cloning or expression planning.
The main search box scans gene symbol, UniProt entry, protein name, aliases, family name, topology track, and embedded disease names. The disease-focused search box filters rows by Open Targets disease associations.
Example searches: EGFR, ITGAV, DKK1, OPRM, cadherin, breast cancer.
The Browse page defaults to all rows sorted by PubTator hits from highest to lowest. Search terms narrow the table; Reset clears both search boxes and restores PubTator-hit sorting.
Click table headers to sort by entry, gene, protein name, family, disease score, topology track, PubTator hits, design region, AlphaFold availability, PDB availability, construct count, or cross-reactivity count.
The rows-per-page selector controls table density. Use 10 or 25 for detailed review and 50 or 100 for broad triage.
Secreted, GPI-anchored, and single-pass proteins usually emphasize soluble antigen constructs from the mature secreted protein or extracellular region. Multipass proteins include a membrane-expression track, and mixed cases with large extracellular regions also include soluble extracellular-region constructs.
For multipass targets, do not interpret the soluble construct list as a complete expression strategy. Review the membrane-expression suggestions and full-length context.
Public OpenAntigens releases are static HTML snapshots. They can be browsed locally or hosted as ordinary static files, and the visible pages represent the data available at the recorded release date.
Browser-based refresh controls are not part of the public release interface. Updated annotations are incorporated in the next scheduled release.
| Section | What it tells you | How to use it |
|---|---|---|
| Target / Design Region | Resolved UniProt target, organism, sequence length, topology-derived design scope, links, PubTator count, and source identifiers. | Confirm target resolution and compare the extracellular, secreted, or membrane scope with the planned design. |
| Interactive Construct Builder | Linked sequence, cysteine/furin warnings, copy-ready sequence exports, and structure/pLDDT/PAE panels when compatible local structure assets exist. | Adjust boundaries and export human, mouse, and cynomolgus monkey-equivalent constructs. |
| Open Targets Disease Associations | Indirect and direct disease associations and scores from Open Targets. | Treat scores as disease-association context; therapeutic validation requires separate evidence. |
| Homology | Human-to-mouse and human-to-cynomolgus monkey equivalent regions when reference mappings are available. | Review conservation, boundary transfer, and cross-species reagent risk before animal screening or validation. |
| Cross-reactivity | Local BLAST hits ranked by bit score, with identity, coverage, E-value, coordinates, and alignment text. | Inspect high-scoring non-self hits before prioritizing antibody-discovery antigens. |
| Cysteines / PTMs / Furin sites | Potential expression liabilities, curated UniProt PTM or processing annotations, and optional mutation guidance. | Review warnings before ordering constructs. Optional Cys-to-Ser and furin-site edits in the builder update names and sequences in real time. |
| Family Context | Canonical family/paralog context and directional identity matrix when available. | Identify close paralogs that may create specificity risks or useful comparison antigens. |
| Interactions / Assembly | Known interaction or complex context, including possible obligatory partners when evidence supports it. | Flag proteins that may require co-expression, partner chains, or extra caution when designing isolated soluble constructs. |
| Construct Summary / Constructs | Precomputed construct classes, boundaries, homolog-equivalent sequences, images, and sequence exports. | Review construct classes in display order, then refine boundaries in the builder when needed. |
Reports list constructs in a fixed priority order, and reviewing them in that order works well: full design region, then PDB-backed, domain annotated, strict calculated, and lenient calculated constructs. For multipass proteins, review membrane-expression constructs separately from soluble extracellular-region constructs. The Pre-generated Constructs page explains why each class sits where it does and how to choose between them.
Favorable soluble constructs usually have strong pLDDT across the region, low internal PAE, boundaries near curated domain edges or PDB precedent, no transmembrane/cytoplasmic contamination, no unexpected unpaired cysteines, and manageable cross-reactivity to paralogs.
Be cautious with constructs dominated by low pLDDT, high internal PAE, long disordered linkers, unresolved topology, dense basic furin-like motifs, unpaired cysteines, very high similarity to unwanted paralogs, or missing ortholog mappings for planned animal work.
pLDDT tells you whether AlphaFold is locally confident at each residue. High pLDDT supports local fold confidence, but it does not prove that two domains have a fixed relative orientation.
PAE reports AlphaFold's estimated uncertainty in relative placement between residues or regions. Low PAE within a block supports a cohesive structural unit; high PAE between blocks often marks flexible domain motion.
| Goal | Recommended workflow |
|---|---|
| Find antibody-discovery antigen candidates | Search the gene or disease, filter for structure availability, inspect full design-region and PDB-backed constructs, then review cross-reactivity and homolog-equivalent sequences. |
| Design a compact domain antigen | Open the report, start with domain annotated and strict calculated constructs, inspect pLDDT/PAE boundaries, and export TSV/FASTA from the builder. |
| Prioritize cross-species screening constructs | Check human, mouse, and cynomolgus monkey sequences in the Live Selected Region, then prioritize constructs with high identity and conserved boundaries. |
| Avoid paralog cross-reactivity | Use Family Context and BLAST Cross-reactivity together. The family matrix gives paralog-level context; BLAST alignments show local high-similarity regions. |
| Handle a multipass protein | Look for a large extracellular region if present, then separately review membrane-expression constructs, full-length AlphaFold context, full-length BLAST, and GPCR/membrane engineering suggestions. |
| Review release-state gaps | If a report is pending, failed, or missing a structure, treat that as a property of the current release snapshot and check future releases for updates. |
Search EGFR, open EGFR_HUMAN, compare full extracellular-region and domain constructs, inspect PDB-backed boundaries, and check ERBB family context before choosing an antigen for antibody discovery.
Search ITGAV, review interaction and assembly context carefully, and treat isolated integrin-alpha constructs cautiously because integrins often require beta-chain context for native assembly.
Search DKK1 to see how secreted proteins are handled. Focus on mature extracellular sequence, cysteine-rich domains, disulfide context, and compact domain constructs.
Search OPRM for a multipass example. Prioritize full-length membrane-expression context and treat short loops differently from soluble extracellular-region antigens.
| Problem | Likely reason | What to do |
|---|---|---|
| Report is pending or failed | The target could not be completed for the current release because of source-data limitations, structure mismatch, or processing failure. | Inspect the error column and available raw JSON. The target may be resolved in a later release. |
| AlphaFold is missing | No canonical AlphaFold model was found or the available model did not match the canonical UniProt sequence. | Use PDB/domain evidence if available, or refresh the target after source-reference updates. |
| Homolog sequence is missing | The ortholog reference table lacks a usable canonical sequence or mapping for that species. | Use human-only design until the ortholog table is updated, or inspect source identifiers manually. |
| Family matrix is absent | No canonical family was identified, the family exceeded the configured size limit, or precomputed paralog data are unavailable. | Review BLAST local similarity and InterPro domain annotations for specificity context. |
| Cross-reactivity list is long | The query region is highly conserved, contains common domains, or the full-length track captured broad family similarity. | Sort by bit score, inspect alignments, and focus on high-identity hits overlapping the selected construct. |
| Construct looks biologically wrong | Automated heuristics can miss ligand sites, partner requirements, topology edge cases, or literature-specific constraints. | Use the builder to adjust boundaries and check Methods for the exact evidence sources and limitations. |
Use the Builder guide for detailed instructions on sequence/structure selection, pLDDT, PAE, Cys-to-Ser edits, and FASTA/TSV exports.
Use the Methods page for source databases, construct heuristics, BLAST setup, family/paralog logic, update cadence, and limitations.
Use the Constructs page for the dedicated explanation of pre-generated construct classes, structural diagnostics, homolog transfer, PTM-aware review, and limitations.
Use the Downloads page for the portal index, manifest, and flat files that support reproducible downstream analysis.
Use the Terms page for software license, generated annotation license, source-data terms, and contact information.
