Discover receptor–ligand pairs, identify cell-surface drug targets, and clarify mechanism of action (MoA) with a genome-scale screening workflow designed for extracellular protein interactions.
Our service supports end-to-end delivery—from project design and primary screening to hit prioritization, confirmation, and optional orthogonal validation—so you can move quickly from a biological question to actionable candidates.
Best for
Genome-wide cell surface interaction screening is a high-throughput approach to identify specific extracellular binding partners at scale—typically focusing on membrane receptors, GPI-anchored proteins, and other surface-accessible proteins, and/or secreted ligands depending on the library design.
Unlike many intracellular PPI methods, this screening strategy is built around surface-accessible, extracellular interactions, making it especially suitable for:
Note: "Genome-wide" coverage is library-dependent. We define the target space with you during project setup and align screening strategy, controls, and validation to your scientific goal.
This service is designed to answer questions such as:
Genome-scale discovery, not guesswork
Screen large target spaces (library-dependent) to uncover novel receptor–ligand pairs.
Built for extracellular biology
Optimized for surface-accessible interactions and receptor–ligand binding rather than intracellular complexes.
Designed to capture low-affinity interactions
Assay formats can be tuned for weaker extracellular binding (project-dependent).
Clear evidence for decision-making
Ranked hit lists with supporting evidence help you quickly select candidates for validation and functional studies.
Optional orthogonal validation
Confirm binding using independent methods (e.g., flow cytometry, SPR/BLI, ELISA) to strengthen confidence.
Choose the target space based on your scientific question. Library size and coverage are platform-dependent and will be confirmed during feasibility review.
Best for: finding the receptor(s) of a secreted ligand, cytokine, growth factor, or Fc-fusion.
Input: purified ligand / Fc-fusion / tagged bait.
Output: ranked list of candidate surface binders with control-filtered evidence.
Best for: deorphanizing receptors or identifying which surface targets bind your bait.
Input: ligand, antibody, or engineered binder.
Output: prioritized receptor candidates with confirmation-ready readouts.
Best for: faster iteration or hypothesis-driven screening (e.g., cytokine receptors, immune checkpoints, GPCR subsets).
Input/Output: defined case-by-case for speed and cost efficiency.
Assay format is selected based on bait type, expected binding strength, and whether membrane-protein context is required. Available options include:
For each project, we define clear hit-calling criteria (signal-to-background, reproducibility, and control separation) before screening begins.
Project consultation & feasibility review
Define goals, target space, bait format, assay strategy, controls, and success criteria.
Pilot setup (when needed)
Confirm bait integrity/behavior and establish assay conditions and control performance.
Primary genome-wide screen
Run the screen against the defined target space and capture primary signals.
Hit ranking and triage
Generate a prioritized candidate list based on signal strength, reproducibility, and specificity.
Confirmation (secondary screening)
Re-test top candidates with additional stringency and controls to remove artifacts.
Optional orthogonal validation
Validate binding using independent methods (flow cytometry, SPR/BLI, ELISA) to strengthen confidence.
Final reporting
Deliver ranked hits, evidence summaries, and recommended next steps.
To ensure confident hit calling, we apply a control-first QC strategy:
This approach yields a ranked candidate set with clear separation from background.
Orthogonal validation confirms prioritized hits using an independent assay to strengthen confidence:
Output: validation plots/data with control context and an interpreted conclusion for each tested hit.
| Criteria | Genome-wide Cell Surface Screening | Co-IP | SPR | Protein Microarrays |
| Application | Receptor–ligand pairing, target discovery, low-affinity interactions | Protein–protein interaction validation | Kinetics and affinity analysis | High-throughput screening, antibody profiling |
| Sensitivity | High (avidity-based binding for weak interactions) | Moderate (dependent on antibody quality) | High (real-time detection) | Moderate (best for high-affinity targets) |
| Specificity | High (bait vs control, competition assays) | Moderate (prone to background contamination) | High (precise affinity measurement) | Moderate (depends on antibody selection) |
| Confirmation Methods | Flow cytometry, SPR, BLI, ELISA (optional validation) | Western blot (WB) | Real-time kinetic/affinity measurement (SPR) | Microarray analysis |
| Advantages | Scalable, high-throughput, identifies low-affinity interactions, built-in validation | Effective for validating known interactions, stable complexes | Ideal for precise affinity and kinetics studies | High throughput, but lacks in vivo context |
| Bait type | Typical use | Recommended info to provide |
| Recombinant ligand / ECD protein | Receptor discovery, ligand–receptor pairing | Sequence/construct, tag/Fc format, expected MW, species |
| Fc-fusion / engineered binder | Cell-surface binding discovery, cross-reactivity checks | Fc type, tag, glycosylation notes (if known), target hypothesis |
| Antibody (IgG / mAb) | Target identification (MoA), surface target mapping | Isotype, species, concentration, known binding behavior |
Receptor–Ligand Pairing
Map ligand-to-receptor interactions to accelerate pathway elucidation and target selection.
Orphan Receptor Deorphanization
Identify candidate ligands for orphan receptors to unlock biology and therapeutic opportunities.
Target Identification (MoA) for Biologics
Determine binding targets for antibodies, ADCs, and engineered proteins to support MoA and de-risk off-target concerns.
Cell–Cell Communication Mapping
Prioritize extracellular interaction pairs relevant to immune signaling, inflammation, and tumor microenvironment biology.
Cell-surface Target Discovery & Biomarker Identification
Nominate surface-accessible targets for therapeutic development or diagnostic applications.
Pathogen/Toxin/Particle Receptor Discovery
Identify surface factors involved in binding and entry (project scope defined by assay format and biosafety requirements).
Primary Screen Hit Ranking
Primary screen hit ranking showing clear bait–control separation and a defined calling threshold (mean ± SD, n=3).
Confirmation / Competition Binding
Dose-dependent binding and competition inhibition confirm specific target engagement (mean ± SD, n=3).
Flow Cytometry Cell-binding Validation
Flow cytometry validation shows a binding shift in target-positive cells and signal reduction with competition.
Interactome Specificity Volcano Plot（Bait vs Control）
Volcano plot highlights significantly enriched hits in bait vs control with defined log2FC and p-value thresholds.
How does genome-wide screening capture low-affinity extracellular interactions?
Many cell-surface interactions are weak and transient (often µM-range K_D with fast off-rates). We enhance detection using avidity-based binding (e.g., multimerized baits such as Fc-fusions or streptavidin-clustered tags), improving signal-to-noise and enabling interactions that may be missed by Co-IP or standard SPR.
Can this service identify targets for bispecific antibodies or ADCs?
Yes. Using the therapeutic molecule as the bait against a cell-surface library, we can identify the primary target and assess potential off-target binding to other surface-accessible proteins.
Why use cell-based screening instead of purified protein microarrays?
Cell-based formats present receptors in a more native context, supporting proper folding and key PTMs (e.g., glycosylation). This is especially important for GPCRs, multi-pass membrane proteins, and ion channels, which can lose epitopes when purified or immobilized.
What distinguishes a "hit" from non-specific background binding?
We use a control-first hit-calling strategy:
This helps filter common "sticky" binders and technical artifacts.
Is the screening limited to human protein libraries?
Human-focused libraries are standard, but custom species libraries (e.g., mouse, rat, NHP) can be supported for cross-species reactivity studies. Pathogen-related target spaces may also be possible depending on scope and feasibility.
Can whole cells or viral particles be used as bait?
In some projects, yes. The workflow can be adapted for particle-to-cell screening (e.g., AAV/lentiviral vectors, exosomes), provided a suitable detection strategy is available and feasibility is confirmed.
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