overview of the dataset in the paper :
15,789 de novo variants
- 12166 in 6430 affected individuals.
- 5951 SNVs in our autosomal coding windows.
- 3623 in 2179 unaffected individuals.
- 12166 in 6430 affected individuals.
Annotations and RR:
- protein-coding autosomal syn + Mis + PTV (‘splice_donor_variant’, ‘splice_acceptor_variant’, ‘stop_gained’, ‘frameshift_variant’)
In our TADA-A model, we used the 5951 DNMs. (n_sample = 6430)
paper_obs: the observed number of mutations in the paper.
our_obs: the observed number of mutations in our model.
In the paper, the amount of mutations in these catagories is 7131, while only 5743 of them are of SNV located in our autosomal coding windows.
backgrd: the expected number of background mutations after using the synonymous mutations to calibrate the rates.
burden: $burden = \frac{our_obs}{backgrd}$
calculated_RR: RR calculated by the formula gamma = 1 + (lambda - 1)/pi
est_RR: RR separately estimated by TADA-A model.
1 | df |
| annota (VEP) | paper_obs | paper_percent | paper_logRR | paper_RR | our_obs | our_percent | backgrd | burden | calculated_RR | log_est_RR | est_RR |
|---|---|---|---|---|---|---|---|---|---|---|---|
| <fct> | <fct> | <fct> | <dbl> | <dbl> | <dbl> | <dbl> | <dbl> | <dbl> | <dbl> | <dbl> | <dbl> |
| PTV_Highest(pLI=0.995-1) | 366 | 5.13 | 3.9231690 | 50.560417 | 123 | 2.14 | 33 | 3.7273 | 55.546 | 3.476063000 | 32.332179 |
| PTV_Middle(pLI=0.5-0.995) | 164 | 2.30 | 1.9223090 | 6.836726 | 49 | 0.85 | 29 | 1.6897 | 14.794 | 2.293976000 | 9.914279 |
| PTV_Lowest(pLI=0-0.5) | 442 | 6.20 | 0.9713427 | 2.641489 | 145 | 2.52 | 100 | 1.4500 | 10.000 | 1.687930000 | 5.408274 |
| Missense_Highest(MPC≥2) | 354 | 4.96 | 3.0978370 | 22.149989 | 278 | 4.84 | 181 | 1.5359 | 11.718 | 2.250359000 | 9.491143 |
| Missense_Middle(MPC=1-2) | 894 | 12.54 | 1.4303100 | 4.179995 | 694 | 12.08 | 598 | 1.1605 | 4.210 | 1.379533539 | 3.973048 |
| Missense_Lowest(MPC<1) | 3155 | 44.24 | NA | NA | 2870 | 49.97 | 2333 | 1.2302 | 5.604 | 1.171609570 | 3.227183 |
| Synonymous | 1756 | 24.62 | 0.1190180 | 1.126390 | 1584 | 27.58 | 1584 | 1.0000 | 1.000 | 0.009975216 | 1.010025 |
| Total | 7131 | 100.00 | NA | NA | 5743 | NA | 4858 | NA | NA | NA | NA |
burden of DeepSEA PTM
1 | new.df |
| RBP | obs | backgrd | burden | calculated_RR | log_calculated_RR | log_estimated_RR | estimated_RR |
|---|---|---|---|---|---|---|---|
| <fct> | <dbl> | <dbl> | <dbl> | <dbl> | <dbl> | <dbl> | <dbl> |
| ago_adult_brain.BA4.hg19 | 122 | 101 | 1.207921 | 5.158416 | 1.640630 | 0.01784533 | 1.018006 |
| ago_adult_brain.Cingulate.gyrus.hg19 | 133 | 102 | 1.303922 | 7.078431 | 1.957052 | 0.02456046 | 1.024865 |
1 | df |
| annota | pro_VEP | sibling_VEP | burden | paper_burden |
|---|---|---|---|---|
| <fct> | <dbl> | <dbl> | <dbl> | <dbl> |
| syn | 1537 | 678 | 0.7682285 | 1.0068929 |
| MPC2 | 278 | 53 | 1.7775228 | 2.0683381 |
| MPC12 | 698 | 250 | 0.9461537 | 1.1652267 |
| MPC01 | 2909 | 1354 | 0.7280669 | 0.9835945 |
| PTV>0.995 | 123 | 9 | 4.6313634 | 3.5437192 |
| PTV-0.5-0.995 | 51 | 12 | 1.4402411 | 1.3555210 |
| PTV<0.5 | 164 | 76 | 0.7312679 | 0.9985671 |