National Biodiversity Institute

A CRISPRi guide-efficacy model trained in K562 cells barely transferred to the independent Dolcetto library from Sanson et al. 2018 in HT29 and A375 cells, reaching Spearman correlations of only 0.008 and 0.012. Keeping the same 101 features, architecture and hyperparameters but replacing the within-gene percentile label with a continuous cross-study z-score raised transfer to 0.136 in HT29 and 0.158 in A375, and leave-one-chromosome-out performance in K562 from 0.375 to 0.429. The transfer failure therefore traces mainly to label design rather than missing chromatin features.

A CRISPRi guide-efficacy model trained in K562 cells barely transferred to the independent Dolcetto library from Sanson et al. 2018 in HT29 and A375 cells, reaching Spearman correlations of only 0.008 and 0.012. Keeping the same 101 features, architecture and hyperparameters but replacing the within-gene percentile label with a continuous cross-study z-score raised transfer to 0.136 in HT29 and 0.158 in A375, and leave-one-chromosome-out performance in K562 from 0.375 to 0.429. The transfer failure therefore traces mainly to label design rather than missing chromatin features.