To compare the gene scores computed by the two methods, we increased the maximum number of Monte Carlo runs for VEGAS to 108, at a high computational cost (about 9 days of runtime). We observed excellent concordance between the gene scores of Pascal and VEGAS, except for scores below 10−6: since we restricted VEGAS to 108 Monte Carlo runs, it could not estimate p-values smaller than 10−6 with good precision (Fig 2B). In contrast, Pascal can compute gene scores with high precision for p-values down to 10−15. In summary, the analytic solutions incorporated in the Pascal algorithm offer a dramatic increase in efficiency and precision. Direct comparison of the sum and max gene scores of Pascal revealed good concordance between the two scoring methods. In cases where the results of two methods disagree, max scores tend to be more significant (S3 Fig).
