0821_tadaA_res

all separate estimation

setwd("/storage11_7T/fuy/TADA-A/annotation")
a = readRDS(paste0("/storage11_7T/fuy/TADA-A/annotation/2020-08-28","_all_RR.rds"))
b = readRDS("denovo_df.rds")
d = rbind(a,b)
e = d[order(-d$relative_risk),]
e$idx = 1:nrow(e)
e

A data.frame: 22 × 5

	relative_risk	lower_bound	upper_bournd	annota	idx
	<dbl>	<dbl>	<dbl>	<chr>	<int>
23	7.4680424	7.1881892	7.7478955	denovo_pLI05-995	1
32	7.1675188	7.0101995	7.3248381	denovo_pLI05	2
42	7.1059856	6.9848262	7.2271450	denovo_MPC2	3
15	7.0805459	6.8943693	7.2667226	denovo_pLI995	4
13	7.0467099	6.9035710	7.1898489	denovo_PTV	5
51	3.1078241	1.6900099	4.5256384	pLI_nlt_995	6
41	2.2739992	1.6665827	2.8814158	pLI_lt05	7
22	2.2615612	1.6800949	2.8430276	gnomad.v2.1.1.all_lofs	8
14	2.1166764	-0.2095761	4.4429289	pLI_nlt_09	9
2	1.8723460	1.6331143	2.1115778	annova_lof	10
7	1.8200768	1.5566559	2.0834977	MPC_gt2	11
6	1.4764815	1.2682661	1.6846969	spidex_lt10	12
3	1.3286583	1.0802172	1.5770995	ccr_90	13
4	1.2019536	1.0027889	1.4011183	MVP75	14
9	1.1630679	-1.2117190	3.5378548	CLIPdb005	15
5	1.0677442	0.7807190	1.3547694	PrimateAI80	16
21	0.8484629	0.7036579	0.9932679	annova_mis_lof	17
8	0.1276963	-1.7924259	2.0478185	ribosnitch01	18
31	-1.0000000	-9.9236275	7.9236275	pLI_05_995	19
11	-1.0000000	-1.6844744	-0.3155256	annova_syn	20
1	-1.0000000	-1.7410982	-0.2589018	annov_missense	21
12	-1.0000000	-5.8501671	3.8501672	RBP01	22

error

“CADD15”,”MPC12”,”MPC01”

Error in solve.default(-mle$hessian): Lapack routine dgesv: system is exactly singular: U[1,1] = 0
Traceback:

1. TADA_A_RR_estimate(data = compact_data$base_info, selected_annotations = c(i),
   . gene_prior_file = “prior/uniform_gene_prior.txt”, optimization_iteration = 2000)
2. solve(-mle$hessian)
3. solve.default(-mle$hessian)

denovo pLI and MPC as the paper presented

b

A data.frame: 4 × 4

relative_risk	lower_bound	upper_bournd	annota
<dbl>	<dbl>	<dbl>	<chr>
7.080546	6.894369	7.266723	denovo_pLI995
7.468042	7.188189	7.747895	denovo_pLI05-995
7.167519	7.010200	7.324838	denovo_pLI05
7.105986	6.984826	7.227145	denovo_MPC2

pLI

• pLI is from pLI.gnomad.v2.1.1.lof_metrics.by_gene
• lof snv is from pLI.gnomad.v2.1.1.lof.snv.bed
• odd: pLI [0.5,0.995)

e2[c(2,5,15,3),]

A data.frame: 4 × 5

	relative_risk	lower_bound	upper_bournd	annota	idx
	<dbl>	<dbl>	<dbl>	<chr>	<int>
51	3.107824	1.6900099	4.525638	pLI_nlt_995	2
14	2.116676	-0.2095761	4.442929	pLI_nlt_09	5
31	-1.000000	-9.9236275	7.923628	pLI_05_995	15
41	2.273999	1.6665827	2.881416	pLI_lt05	3

lof and missense

e2[c(4,6,13,17),]

A data.frame: 4 × 5

	relative_risk	lower_bound	upper_bournd	annota	idx
	<dbl>	<dbl>	<dbl>	<chr>	<int>
22	2.2615612	1.6800949	2.8430276	gnomad.v2.1.1.all_lofs	4
2	1.8723460	1.6331143	2.1115778	annova_lof	6
21	0.8484629	0.7036579	0.9932679	annova_mis_lof	13
1	-1.0000000	-1.7410982	-0.2589018	annov_missense	17

PTV

e2[c(11,14,18),]

A data.frame: 3 × 5

	relative_risk	lower_bound	upper_bournd	annota	idx
	<dbl>	<dbl>	<dbl>	<chr>	<int>
9	1.1630679	-1.211719	3.537855	CLIPdb005	11
8	0.1276963	-1.792426	2.047818	ribosnitch01	14
12	-1.0000000	-5.850167	3.850167	RBP01	18

number of risk genes

• FDR <= 0.1

df

A data.frame: 4 × 2

gene_count	annota
<dbl>	<fct>
239	denovo_pLI_snv, gnomad.v2.1.1.all_lofs, pLI_lt05_gnomad.v2.1.1.all_lofs, pLI_nlt_995_gnomad.v2.1.1.all_lofs, MPC_gt2
500	denovo_pLI_nlt995_snv, denovo_pLI_05_0995_snv, denovo_pLI_lt05_snv, denovo_MPC_gt2
246	denovo_pLI_snv, gnomad.v2.1.1.all_lofs, pLI_lt05_gnomad.v2.1.1, pLI_nlt_995_gnomad.v2.1.1, all_lof, MVP75, primateAI80, spidex10, MPC_gt2
9	gnomad.v2.1.1.all_lofs, pLI_lt05_gnomad.v2.1.1, pLI_nlt_995_gnomad.v2.1.1, MPC_gt2