Extended Data Fig. 4: Radiotherapy responsive modulation of YC transcription initiation correlates with CRC clinical response.
a, Expanded version of Fig. 4a, illustrating the dynamics of total YC/YR TPM values upon irradiation for all 5 organoid samples. b, Dual initiator promoters with a dynamic shift in YC vs YR transcript abundance, upon irradiation, correlating with radiotherapy responsiveness (as illustrated in Fig. 4c) were identified (n = 411). The criteria used was that the average fold change in YC:YR ratio upon irradiation in CRC1&2 (responsive) for each dual initiator was 1.5 fold greater than the ratio in CRC3 (moderately responsive), which was in turn 1.5 fold greater than the YC:YR ratio fold change upon irradiation in CRC4 and 5 (non-responsive). A heatmap of the relative fold change in YC:YR ratio upon irradiation for each dual initiator, between CRC organoid samples is shown. c, Bar graph of biological process gene ontology of dual initiators displaying dynamic YC:YR ratio change upon irradiation correlated with radiotherapy responsiveness (as described in b). c, Bar graph of the gene ontology of dual initiators displaying dynamic YC:YR ratios correlated with radiotherapy responsiveness (as described in b). Matches to the Molecular signature database (MSigDB) Hallmark gene sets (bottom) are shown. Dotted line shows 0.05 FDR threshold.
