Extended Data Fig. 4: High-throughput CRISPRi screening identified functional CREs essential for CRC cell proliferation and Polygenic Risk Stratification of CRC and precancerous lesions.
a. Relative mRNA expression of Cas9 in different types of cell lines. Data were shown as the median, box limits indicate upper and lower quartiles and whiskers indicate the maximum and minimum, n = 9 biologically independent samples. The P values were calculated by unpaired two-sided Student’s t-test. b. Relative protein expression of Cas9 in different types of cell lines. c-d. Correlation of sgRNA counts between replicates at two time points in SW480 (c) and HCT116 (d) cells. The x- and y-axis denote the sgRNA counts of replicates at day 0 and day 16. The two-sided P values were calculated using Pearson analysis. e-f. Correlation of epigenomic signals with the negative RRA score in SW480 (e) and HCT116 (f) cells. The two-sided P values were estimated using Pearson correlation test. The color of the box denotes the correlation coefficient. g. The number of functional CREs across three stages in the seven different types (C1-C7). h. HRs for incident CRC risk of individuals from each PRS group by comparing with those in the bottom 20% under PRS323 in UK Biobank CRC cohort, n = 380,525. i-j. HRs for incident non-advanced adenoma (i) and advanced neoplasm (j) risk from each PRS group by comparing with those in the bottom 20% under PRS323 in PLCO cohort, n = 14,071. k. HRs for incident CRC risk of individuals from each PRS group by comparing with those in the bottom 20% under PRS224 in UK Biobank CRC cohort, n = 380,525. l-m. HRs for incident non-advanced adenoma (l) and advanced neoplasm (m) risk from each PRS group by comparing with those in the bottom 20% under PRS224 in PLCO cohort, n = 14,071. Participants were divided into low (bottom 20%), intermediate (middle 60%), and high-risk (top 20%) groups. The two-sided P values and HRs of CRC and precancerous lesions risk were calculated using Cox’s proportional hazards regression models (h-m).
