Fig. 2: Identification of antibody targets. | Nature Communications

Fig. 2: Identification of antibody targets.

From: Accelerating target deconvolution for therapeutic antibody candidates using highly parallelized genome editing

Fig. 2

a MAGeCK gene enrichment scores for all genes across the 39 test mAbs. Target genes selected using our three criteria indicated in red, MHC class I dependency genes in pink. b Representative example showing enrichment of high MAGeCK scores among MHC class I dependency genes for a mAb against the MHC class I complex (mAb19). MAGeCK false discovery rate (x-axis) vs gene enrichment score for identified MHC class I specific antibody mAb19 (y-axis). Target genes selected using our three criteria indicated in red, MHC class I dependency genes in pink. c MHC class I enrichment score, calculated as ‒log10(P-value) for one-sided Wilcoxon rank-sum test for MAGeCK scores for our 11 selected MHC class I dependency genes vs other genes in the genome. As shown, we observed significantly higher enrichment scores for mAbs confirmed to target MHC class I (n = 9) compared to antibodies with non-MHC targets (n = 25; **** Indicates P < 0.0001 by one-sided Wilcoxon rank-sum test; exact P-value 5.5 × 10−6). Based on this observation, we infer that four antibodies (right) that showed high MHC class I enrichment scores but whose specificity could not be validated experimentally (n = 4) also target MHC class I. d Histogram of the rankings of the best-scoring gene representing the target in the MAGeCK analysis across the 38 resolved mAbs. Source data are provided as a Source Data file.

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