Fig. 7: Evaluation of TYPEx performance in cell phenotyping and benchmarking against alternative approaches.

a–c Validation of TYPEx using orthogonal TRACERx data. Correlation of whole-exome sequencing (WES)-derived T-cell percentages calculated using T cell ExTRECT with the IMC-derived T-cell percentage on paired regional TMA tumour cores (a). Correlation of immunochemistry (IHC)-derived CD3⁺ cells with the T-cell density in the stromal area (b) or the proportion of T cells over all cells in the intraepithelial area (c) detected from IMC on paired regional TMA cores (T cells & Stroma panel). d Comparison of cell densities calculated with TYPEx between two antibody panels from serial tissue sections within the TRACERx 100 cohort. The heatmap shows Spearman correlation coefficients between cell densities of markers and samples profiled with the Pan-Immune and T cells & Stroma panels. e Cell subtype annotations from TYPEx and published manually adjusted annotations from X-shift were correlated with the cell counts of annotations derived from manual gating in the CRC CODEX dataset (Spearman correlation). f Comparison of clustering approaches with TYPEx with and without the stratification by confidence step (no strat). The fraction of Ambiguous and Unassigned cells in TRACERx 100 IMC (left) and CODEX (right) data were annotated according to the D score-derived positivity or published cell annotations (Schürch et al.). g The fraction of double-positive T cells derived from TYPEx compared to the three clustering approaches in the TRACERx 100 IMC cohort (n = 275 cores, T cells & Stroma panel). h Performance metrics F1-scores per cell subtype on the CRC CODEX dataset (n = 70 cores/TMA). CELESTA metrics on the TMA A cores were derived from a published confusion matrix (Zhang et al.). Dashed lines show the macro F1-scores across cell subtypes for each method. i Performance metrics F1-scores per cell subtype on Barrett’s oesophagus (BE) CODEX data. j, Macro F1-scores for the three validation datasets. STELLAR scores were published previously (Brbić et al.). a–c ⍴ represents Spearman correlation coefficient with unadjusted p values. Source data are provided as a Source Data file. TILs tumour-infiltrating lymphocytes, H&E haematoxylin and eosin, CRC colorectal cancer, WSI whole-slide image.