Investigating sQTL analysis results of interest: a deeper look¶

From this notebook we've got some examples, particularly for the 4 QTL case where the smallest p-value has small PIP, and it seems to be driven by adjunct signal clusters. We want to see if SuSiE's results makes more sense, specifically if it falls in splice sites.

%cd /project/compbio/jointLCLs/results/SuSiE/fastqtl_qqnorm_ASintron_RNAseqGeuvadis_YangVCF_100Kb

/project/compbio/jointLCLs/results/SuSiE/fastqtl_qqnorm_ASintron_RNAseqGeuvadis_YangVCF_100Kb

4 QTL case¶

Notice that below is the same intron cluster as the 5 QTL case above. It has perfectly correlated signals. The top z-score has PIP zero.

%preview SuSiE_CS_4/AS_chr12_27542229_27543032_clu_562.png

Load data and get positions of interest¶

Load SuSiE results

dat = readRDS('SuSiE_CS_4/AS_chr12_27542229_27543032_clu_562.rds')

names(dat)

Load input data

print(dat$input)
input = readRDS(dat$input)

[1] "/project/compbio/jointLCLs/results/SuSiE/fastqtl_qqnorm_ASintron_RNAseqGeuvadis_YangVCF_100Kb/chr12/chr12_27542229_27543041.rds"

sapply(1:length(input), function(i) input[[i]]$uname)

So it is the 2nd data-set in the input intron cluster that we are interested in.

input = input[[2]]
input$uname

Now let's identify the SNP having the largest z-score,

which.max(abs(input$z_score))

and the ones in SuSiE CS:

dat$sets$cs

interested = as.vector(unlist(dat$sets$cs))
interested

names(input$z_score)[interested]

UCSC query¶

Now let's focus on the one SuSiE SNP (rs11049018_chr12_27612107_A_G) nearest to the top z-score (rs55880072_chr12_27612517_A_C), . PIP of this SNP is 1. We check in UCSC browser chr12:27,612,000-27,612,600 that includes both this and the top SNP.

%preview ~/tmp/arntl2.png

Hard to argue about anything interesting.

5 QTL case¶

%preview SuSiE_CS_5/AS_chr12_27542229_27543041_clu_562.png

Load data and get positions of interest¶

dat = readRDS('SuSiE_CS_5/AS_chr12_27542229_27543041_clu_562.rds')
input = readRDS(dat$input)
sapply(1:length(input), function(i) input[[i]]$uname)

input = input[[3]]
which.max(abs(input$z_score))

dat$sets$cs

interested = as.vector(unlist(dat$sets$cs))
interested

names(input$z_score)[interested]

We focus on rs67786386_chr12_27616181_C_A vs rs55880072_chr12_27612517_A_C (same as before). We query chr12:27612517-27616381

USCS query¶

%preview ~/tmp/arntl2_right.png

It does fall into DNase I cluster, but nothing interesting beyond this point.

[global]
parameter: fn=path()

[default]
input: fn
R: expand = True
	dat = readRDS({_input:r})
	input = readRDS(dat$input)
	idx = which(sapply(1:length(input), function(i) input[[i]]$uname) == {_input:bnr})
	input = input[[idx]]
	znames = names(input$z_score)
    zidx = which.max(abs(input$z_score))
    print(zidx)
	print(znames[zidx])
	interested = as.vector(unlist(dat$sets$cs))
	print(dat$sets$cs)
	print(znames[interested])

2 QTL case¶

%preview SuSiE_CS_2/AS_chr19_50837358_50838086_clu_8171.png

%sosrun --fn SuSiE_CS_2/AS_chr19_50837358_50838086_clu_8171.rds

rs3219404_chr19_50911461_G_A 
                         737 
[1] "rs3219404_chr19_50911461_G_A"
$L2
[1] 426 434 492 530

$L1
 [1] 372 373 374 375 376 377 380 381 382 386 398 400 414

 [1] "rs10408648_chr19_50856940_G_A"  "rs11881647_chr19_50857469_A_G" 
 [3] "rs115115058_chr19_50874717_G_A" "rs2695120_chr19_50880536_T_C"  
 [5] "rs140533621_chr19_50844210_C_T" "rs144378176_chr19_50844211_A_G"
 [7] "rs147907106_chr19_50844214_C_T" "rs613694_chr19_50844219_C_G"   
 [9] "rs614567_chr19_50844397_C_A"    "rs607307_chr19_50845021_G_A"   
[11] "rs137953380_chr19_50845812_C_A" "rs591161_chr19_50846281_A_G"   
[13] "rs590653_chr19_50846431_A_G"    "rs2546567_chr19_50848093_G_A"  
[15] "rs627400_chr19_50850761_A_G"    "rs625672_chr19_50851155_C_T"   
[17] "rs679288_chr19_50854158_C_T"

%preview SuSiE_CS_2/AS_chr19_54704756_54705028_clu_8215.png

%sosrun --fn SuSiE_CS_2/AS_chr19_54704756_54705028_clu_8215.rds

rs3852890_chr19_54709944_G_A 
                         326 
[1] "rs3852890_chr19_54709944_G_A"
$L2
[1] 312

$L1
[1] 320 322 326

[1] "rs60811961_chr19_54704775_C_G" "rs3852889_chr19_54708430_A_G" 
[3] "rs10424181_chr19_54709277_C_A" "rs3852890_chr19_54709944_G_A"

%preview ~/tmp/rps9.png

SuSiE signal falls in the "Layered H3K27AC" peak.

%preview SuSiE_CS_2/AS_chr20_20007563_20013746_clu_9197.png

%preview SuSiE_CS_2/AS_chr20_37055833_37059684_clu_9365.png

%sosrun --fn SuSiE_CS_2/AS_chr20_37055833_37059684_clu_9365.rds

rs62203382_chr20_37071007_A_G 
                          386 
[1] "rs62203382_chr20_37071007_A_G"
$L1
[1] 401

$L2
[1] 504 518

[1] "rs73098016_chr20_37083100_T_A"  "rs59033379_chr20_37133858_G_A" 
[3] "rs113883801_chr20_37143769_C_T"

%preview SuSiE_CS_2/AS_chr20_57570814_57572658_clu_9568.png

%sosrun --fn SuSiE_CS_2/AS_chr20_57570814_57572658_clu_9568.rds

rs151362_chr20_57554311_C_A 
                        171 
[1] "rs151362_chr20_57554311_C_A"
$L3
[1] 233 236 243

$L2
[1] 189 219 227 252

[1] "rs2295357_chr20_57572839_G_T"   "rs139145965_chr20_57573596_C_T"
[3] "rs6070690_chr20_57574816_G_C"   "rs163779_chr20_57558274_T_C"   
[5] "rs184673_chr20_57567543_A_G"    "rs13720_chr20_57570568_G_A"    
[7] "rs191490_chr20_57576180_A_G"

%preview ~/tmp/ctsz.png

%preview ~/tmp/ak310046.png

%preview SuSiE_CS_2/AS_chr22_30822832_30823227_clu_8715.png

%sosrun --fn SuSiE_CS_2/AS_chr22_30822832_30823227_clu_8715.rds

rs7292432_chr22_30796835_C_G 
                         161 
[1] "rs7292432_chr22_30796835_C_G"
$L2
 [1]  29  30  33  57 118 177 196 276 280 390 394

$L1
[1] 156 168 175 182 197 201

 [1] "rs75265757_chr22_30739174_G_A"  "rs114214629_chr22_30740914_C_G"
 [3] "rs116485157_chr22_30742894_A_G" "rs114429377_chr22_30753931_G_A"
 [5] "rs114302396_chr22_30775694_G_A" "rs116438221_chr22_30808588_G_A"
 [7] "rs78474653_chr22_30823133_G_A"  "rs116255130_chr22_30854639_G_A"
 [9] "rs78467477_chr22_30855806_C_T"  "rs11702947_chr22_30899264_T_G" 
[11] "rs11704977_chr22_30900128_C_T"  "rs2412985_chr22_30792505_C_T"  
[13] "rs4820845_chr22_30800338_T_G"   "rs2299824_chr22_30807524_T_C"  
[15] "rs4820011_chr22_30810954_A_C"   "rs5753130_chr22_30823196_T_C"  
[17] "rs1860215_chr22_30826800_G_A"

30823133 and 30823196 both suggests one exon, in two different CS. There are also a number of other seemly interesting hits.

%preview ~/tmp/22-1.png

%preview ~/tmp/22-2.png

%preview ~/tmp/22-3.png

%preview ~/tmp/22-4.png

%preview SuSiE_CS_2/AS_chr5_130662593_130694902_clu_11986.png

%sosrun --fn SuSiE_CS_2/AS_chr5_130662593_130694902_clu_11986.rds

rs6876350_chr5_130604109_G_T 
                          73 
[1] "rs6876350_chr5_130604109_G_T"
$L1
[1] 115

$L2
[1] 140 155 157 158 197 221 233

[1] "rs6596010_chr5_130625411_G_A" "rs6864145_chr5_130637861_C_T"
[3] "rs6421901_chr5_130648484_A_G" "rs2551036_chr5_130648994_G_A"
[5] "rs9327608_chr5_130650134_G_A" "rs193531_chr5_130674706_C_T" 
[7] "rs1088581_chr5_130682622_G_C" "rs798410_chr5_130684761_A_G"

Just introns, nothing exciting.

%preview SuSiE_CS_2/AS_chr6_29912868_29913011_clu_10776.png

%sosrun --fn SuSiE_CS_2/AS_chr6_29912868_29913011_clu_10776.rds

rs148724924_chr6_29921312_C_G 
                         2607 
[1] "rs148724924_chr6_29921312_C_G"
$L1
 [1]  59  65 121 133 192 196 207 236 253 278 279 283 286 287 288 291 293 294 296
[20] 322 330 333 356 427 437 441 447 449 456 491 511 517 518 544 555 558 566

$L2
 [1] 1747 1765 1770 1794 1813 1816 1833 1834 1847 1849

 [1] "rs116527390_chr6_29817617_A_G" "rs115136886_chr6_29817938_G_A"
 [3] "rs116726743_chr6_29820655_G_T" "rs114182494_chr6_29821370_A_G"
 [5] "rs116357313_chr6_29823998_C_A" "rs114934384_chr6_29824108_T_C"
 [7] "rs116671664_chr6_29824515_G_T" "rs115482696_chr6_29825883_G_A"
 [9] "rs141143417_chr6_29827079_T_A" "rs111597677_chr6_29829251_A_C"
[11] "rs114827325_chr6_29829253_T_C" "rs115133277_chr6_29829507_T_A"
[13] "rs115550313_chr6_29829636_G_T" "rs116799141_chr6_29829813_C_T"
[15] "rs114238229_chr6_29829851_C_T" "rs116629017_chr6_29830045_A_C"
[17] "rs116311746_chr6_29830130_T_C" "rs115735410_chr6_29830213_C_T"
[19] "rs115663981_chr6_29830551_A_G" "rs114018395_chr6_29832119_T_C"
[21] "rs148128960_chr6_29832282_G_A" "rs114732676_chr6_29832407_A_T"
[23] "rs114065755_chr6_29833642_G_A" "rs113452471_chr6_29837763_A_T"
[25] "rs112740109_chr6_29838179_C_A" "rs113143254_chr6_29838335_A_G"
[27] "rs113261027_chr6_29838429_G_C" "rs78610452_chr6_29838461_G_A" 
[29] "rs111555693_chr6_29838650_A_G" "rs140081128_chr6_29839597_G_T"
[31] "rs113479709_chr6_29840810_T_C" "rs113865304_chr6_29841097_T_A"
[33] "rs113581598_chr6_29841103_A_G" "rs113428950_chr6_29842259_A_G"
[35] "rs74584731_chr6_29842573_T_C"  "rs113279442_chr6_29842697_A_C"
[37] "rs111336993_chr6_29843076_G_A" "rs114779893_chr6_29902373_A_G"
[39] "rs113496033_chr6_29902875_T_C" "rs78398725_chr6_29902949_A_C" 
[41] "rs1611338_chr6_29903675_A_C"   "rs112890311_chr6_29904131_A_G"
[43] "rs142543116_chr6_29904180_G_A" "rs114134708_chr6_29904505_T_C"
[45] "rs115656229_chr6_29904528_C_A" "rs114428469_chr6_29905101_G_T"
[47] "rs112863323_chr6_29905121_G_A"

%preview SuSiE_CS_2/AS_chr7_43690311_43695632_clu_10066.png

%sosrun --fn SuSiE_CS_2/AS_chr7_43690311_43695632_clu_10066.rds

rs73108662_chr7_43710433_C_A 
                         241 
[1] "rs73108662_chr7_43710433_C_A"
$L2
[1] 113 122 125 135 137 138 141 144 147

$L3
 [1]  83  84  85  86  90  95 115 116 123 126 127 128 129 130 131 132 136

 [1] "rs11982135_chr7_43636793_G_A"  "rs113544863_chr7_43640420_C_T"
 [3] "rs75881624_chr7_43641750_C_T"  "rs66487644_chr7_43645292_C_A" 
 [5] "rs36113818_chr7_43648723_G_A"  "rs10282065_chr7_43649248_G_A" 
 [7] "rs10242308_chr7_43649889_T_A"  "rs10256980_chr7_43650744_A_G" 
 [9] "rs10231343_chr7_43651155_G_C"  "rs10263267_chr7_43625024_T_G" 
[11] "rs2330875_chr7_43625112_T_A"   "rs10277819_chr7_43625507_A_G" 
[13] "rs10248703_chr7_43625715_C_T"  "rs2330877_chr7_43626911_G_A"  
[15] "rs55673935_chr7_43629282_T_C"  "rs10232453_chr7_43637139_T_C" 
[17] "rs10232580_chr7_43637228_T_C"  "rs11771022_chr7_43641111_C_T" 
[19] "rs12531841_chr7_43642005_T_C"  "rs4724231_chr7_43642214_T_C"  
[21] "rs4724232_chr7_43642414_C_G"   "rs12532021_chr7_43642777_T_C" 
[23] "rs10951735_chr7_43642924_C_T"  "rs10951736_chr7_43643015_A_G" 
[25] "rs10236108_chr7_43643606_T_C"  "rs9655444_chr7_43646273_T_A"

SuSiE signal certainly closer to exons. rs73108662_chr7_43710433_C_A has nothing.

%preview ~/tmp/7-1.png

%preview ~/tmp/7-2.png

%preview ~/tmp/7-3.png