Gradient Biotech

Multiplex IF phenotyping

Turn a multi-channel immunofluorescence image and a completed cell segmentation into per-cell marker positivity, phenotype calls, and region-level composition — beyond what H&E morphology alone can resolve.

Research question

Which marker-positive cell populations are present in this tissue, how do markers co-occur on the same cells, and how does phenotype composition vary across tissue regions?

Who this is for

  • Translational and tumor biology researchers mapping immune or tumor marker panels across tissue
  • Immuno-oncology labs quantifying checkpoint marker-positive populations (e.g. PD-L1+ tumor or stroma)
  • Pharma tissue biomarker teams building marker-panel-based histological endpoints

Data requirements

DataRequiredPurpose
Multi-channel OME-TIFF (multiplex IF)YesPer-channel marker intensity source
Completed Segment cells run for the slideYesCell objects that marker intensity is sampled against
Marker panel configuration (channel → marker name)RecommendedDrives phenotype rule matching; falls back to detected channel names

Workflow

Upload multiplex IF slide → Tiles → Segment cells
  → Multiplex IF phenotyping (marker thresholds + panel)
  → Review phenotype overlay, co-expression, and region composition

Step 1 — Prepare channels and segmentation

Upload the multi-channel OME-TIFF, generate tiles, and run Segment cells so per-cell objects exist for marker sampling. Review per-channel thumbnails and intensity histograms to judge reasonable positivity thresholds before running the pipeline.

Step 2 — Run Multiplex IF phenotyping

On the slide detail page, run Multiplex IF phenotyping against the completed segmentation. Configure the marker panel (channel-to-marker mapping) and per-channel positivity thresholds using the histogram preview; background/autofluorescence correction is applied per channel when enabled.

The pipeline samples marker intensity per cell from its segmented bounding box/centroid, thresholds each channel for positivity, and applies phenotype rules — for example CD8+ T cell, CD68+ macrophage, PD-L1+ tumor/stroma — plus a generic marker-combination fallback for panels without a named rule.

Step 3 — Review phenotypes

Toggle the phenotype map overlay in the slide viewer to see phenotype-colored cells on the WSI. Review the co-expression matrix (how often marker pairs are positive on the same cell) and the region composition table when tissue regions or annotations exist.

Expected outputs

  • Per-cell phenotype table (phenotypes.parquet) with marker positivity and assigned phenotype
  • Marker summary (marker_summary.json) with per-channel positivity rates
  • Region composition (composition_by_region.json) — phenotype frequency by tissue region
  • Phenotype-map overlay for the slide viewer

Typical analyses

AnalysisQuestion
Checkpoint marker mappingWhat fraction of tumor cells are PD-L1+?
T-cell subset mappingWhere are CD8+ T cells concentrated relative to tumor regions?
Marker co-expressionDo CD68 and PD-L1 co-occur on the same myeloid cells?
Panel-wide phenotypingHow does phenotype composition differ between annotated tumor and stroma regions?

Important caveats

Phenotype calls depend on threshold choices, background correction, and segmentation quality — review the marker histograms and overlay visually before treating a phenotype fraction as a stable measurement. This is a research tool, not a validated clinical multiplex assay pipeline.

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