Adjust loop enrichment to remove distance- dependent effect.
Source:R/AllGenerics.R, R/methods-adjustEnrichment.R
adjustEnrichment.RdAdjust loop enrichment to remove distance- dependent effect.
Show diagnostic plot of loop enrichment before and after distance adjustment.
Usage
plotEnrichment(scores, interactions, k = 25, nknots = 10, plot = TRUE)
adjustEnrichment(x, interactions, k = 25, nknots = 10)
# S4 method for DelayedMatrix_OR_matrix,GInteractions
adjustEnrichment(x, interactions, k = 25, nknots = 10)
# S4 method for numeric,GInteractions
plotEnrichment(scores, interactions, k = 25, nknots = 10, plot = TRUE)Arguments
- scores
Numeric vector of enrichment scores.
- interactions
A GInteractions Object containing the interactions used to calculate enrichment scores.
- k
Number of observations for rolling window.
- nknots
integer or function giving the number of knots to use see `?smooth.spline` for more info.
- plot
Boolean (default=FALSE), of whether to show diagnostic plot.
- x
A DelayedMatrix or matrix with enrichment scores.
Value
A DelayedMatrix of enrichment scores where rows are loops and columns are Hi-C files.
A plot (and associated data) for visualizing loop enrichment before and after distance adjustment.
Examples
## Load marinerData
if (!require("marinerData", quietly = TRUE))
BiocManager::install("marinerData")
## Read .hic file paths
hicFiles <- c(
marinerData::LEUK_HEK_PJA27_inter_30.hic(),
marinerData::LEUK_HEK_PJA30_inter_30.hic()
)
#> see ?marinerData and browseVignettes('marinerData') for documentation
#> loading from cache
#> see ?marinerData and browseVignettes('marinerData') for documentation
#> loading from cache
names(hicFiles) <- c("FS", "WT")
## Read in loops as GInteractions object
loops <-
WT_5kbLoops.txt() |>
setNames("WT") |>
read.table(header=TRUE, nrows=1000) |>
as_ginteractions(keep.extra.columns=FALSE)
#> see ?marinerData and browseVignettes('marinerData') for documentation
#> loading from cache
## Removes the "chr" prefix for compatibility
## with the preprocessed hic files
GenomeInfoDb::seqlevelsStyle(loops) <- 'ENSEMBL'
## Calculate loop enrichment
enrich <- calcLoopEnrichment(
x=assignToBins(loops, 100e03),
files=hicFiles
)
#> '0' = foreground;
#> 'X' = background;
#> '*' = both;
#> '-' = unselected
#>
#> X X X X - - - - - - -
#> X X X X - - - - - - -
#> X X X X - - - - - - -
#> X X X X - - - - - - -
#> - - - - - 0 - - - - -
#> - - - - 0 0 0 - - - -
#> - - - - - 0 - - - - -
#> - - - - - - - X X X X
#> - - - - - - - X X X X
#> - - - - - - - X X X X
#> - - - - - - - X X X X
adjustEnrichment(enrich, loops)
#> <1000 x 2> DelayedMatrix object of type "double":
#> FS WT
#> [1,] 1.0374631 1.6937594
#> [2,] 0.9777110 1.4011917
#> [3,] 1.2571415 1.5567901
#> [4,] 1.2220412 0.9160190
#> [5,] 0.7536427 0.7885722
#> ... . .
#> [996,] 1.3596398 0.8349367
#> [997,] 1.2835860 1.0864142
#> [998,] 0.6372802 1.4945152
#> [999,] 1.5484673 0.9612419
#> [1000,] 0.5487884 0.4555145
plotEnrichment(enrich[,1], loops)
#> $rollEnrich
#> rollMedSize rollMedScore
#> <num> <num>
#> 1: NA NA
#> 2: 40000 1.272727
#> 3: 45000 1.240741
#> 4: 50000 1.181818
#> 5: 55000 1.210526
#> ---
#> 216: 1470000 1.000000
#> 217: 1500000 1.000000
#> 218: 1515000 1.000000
#> 219: 1545000 1.000000
#> 220: 1550000 1.000000
#>
#> $splineFit
#> Call:
#> smooth.spline(x = na.omit(re), nknots = nknots)
#>
#> Smoothing Parameter spar= 0.1146557 lambda= 6.375813e-05 (16 iterations)
#> Equivalent Degrees of Freedom (Df): 10.55666
#> Penalized Criterion (RSS): 2.365803
#> GCV: 0.01192468
#>
#> $corrFactor
#> [1] 1.0374631 0.9777110 0.7961896 0.9165309 1.0228008 1.0335348
#> [7] 0.9421412 0.7989606 0.8009662 0.9669477 0.9486945 0.8532821
#> [13] 0.9484175 0.9621551 1.0187595 0.8060715 -2.1223211 0.9401591
#> [19] 0.7989606 0.9120695 0.9285543 1.0024476 0.9847265 0.9650631
#> [25] 0.8359769 0.9238790 0.9301534 0.9039897 0.9927136 0.9165309
#> [31] 0.9338669 0.9196405 0.9120695 0.8960631 0.8807888 0.9665021
#> [37] 1.0067554 0.9709256 0.9146474 0.8992000 1.0067554 0.9691452
#> [43] 1.0123554 0.8734958 0.9559203 0.9497401 0.7973727 0.9709256
#> [49] 0.9452232 0.8532821 0.9214478 0.8680955 0.8857022 0.9452232
#> [55] 0.8960631 0.7959876 0.8046553 1.0314277 1.0062732 0.9777110
#> [61] 1.0389982 0.8471710 0.9385895 1.0287168 0.9421412 0.9179396
#> [67] 0.8471710 0.9404746 0.8217287 1.0402033 1.0388317 0.9421412
#> [73] 0.9143324 0.9580368 0.8261422 0.8924328 0.7952948 0.8941787
#> [79] 0.8734958 0.9120695 0.9156945 0.9927136 0.8139015 1.0306190
#> [85] 0.8359769 1.0067554 0.7984271 0.8308910 0.7973727 0.7954000
#> [91] 0.9691924 0.9669477 0.8912290 0.8532821 1.0383451 0.9754082
#> [97] 0.8686921 1.0314277 1.0270456 0.9691924 0.8104866 0.9216199
#> [103] 0.9617372 0.9404746 0.9927136 0.9458628 0.8664653 0.9120695
#> [109] 1.0270456 0.9853624 1.0123554 0.9691452 0.8001642 0.9619671
#> [115] 1.0358096 0.8139015 0.9980374 0.8664653 0.8261422 1.0389311
#> [121] 0.9497401 1.0062732 0.9263597 1.0335348 1.0337789 0.9799317
#> [127] 1.0433298 0.8807888 1.0067554 0.9181207 1.0358096 0.8972355
#> [133] 0.9777110 1.0389982 0.9617372 0.9165309 1.0335348 0.8960631
#> [139] 0.9665021 0.9799317 0.8060715 1.0187595 0.7973727 0.9431420
#> [145] 0.9777110 0.9165309 0.9385895 0.9368858 0.8682537 0.9600973
#> [151] 0.9534503 1.0374631 0.7949611 0.9537581 0.9646903 1.0309262
#> [157] 0.9421412 0.7973727 0.9980374 0.9535226 1.0335348 2.4930620
#> [163] 0.9179396 1.0400161 0.9754082 1.0337789 0.9799317 0.9977643
#> [169] 0.9404746 0.9980374 1.0389311 0.9927136 0.7961896 0.8807888
#> [175] 0.9887108 0.9853624 0.9368858 0.9537581 0.9580368 0.9703270
#> [181] 0.9196818 0.8664653 0.9486945 0.9646903 1.0256796 0.7954000
#> [187] 0.8176487 0.8807888 0.8703565 0.9368858 0.7949611 0.8060715
#> [193] 1.0187595 0.8217287 0.8471710 0.9778046 0.8009662 0.9202695
#> [199] 0.7954000 0.8734958 0.8414026 0.9558123 0.9691924 0.8034038
#> [205] 0.9927136 0.8308910 0.9421412 0.8308910 1.0385178 0.8597203
#> [211] 0.9537581 0.8883200 1.0358096 0.8217287 0.9214478 0.8883200
#> [217] 0.8060715 1.0123554 0.9154286 1.0178864 0.8176487 0.9698176
#> [223] 0.9932865 0.9452232 0.8060715 0.8359769 0.9890250 1.0123554
#> [229] 0.8261422 1.0109306 0.9039897 0.9617372 0.7952948 0.8883200
#> [235] 0.9853624 0.8074042 0.9431420 1.0306190 1.0215593 1.0067554
#> [241] 0.9946605 0.8139015 1.0337789 0.9452232 0.7949935 1.0372701
#> [247] 1.0149425 0.9763442 0.8308910 1.0178864 0.9431420 1.0314277
#> [253] 0.9632851 0.8139015 0.9156945 0.7973727 0.8261422 0.7949935
#> [259] 0.9320520 0.8022412 0.9619671 0.9927136 0.9636238 0.9202695
#> [265] 0.9997047 0.9452232 0.8960631 0.8471710 0.9120695 0.7952948
#> [271] 0.9694064 1.0223495 0.9799317 0.8883200 0.7949935 0.9659125
#> [277] 0.8532821 0.9535226 0.7984271 0.9230120 0.8359769 0.9238641
#> [283] 0.7954000 0.7952948 0.9509768 0.9690331 0.9665021 0.9600973
#> [289] 0.8471710 1.0385178 0.9181207 0.9617011 0.9404746 1.0187595
#> [295] 0.9170588 0.8060715 1.0178864 0.7970334 0.9181207 1.0357373
#> [301] 0.9277721 0.9036170 0.7970334 0.7989606 0.9154286 0.9677921
#> [307] 0.8960631 0.7970334 1.0024476 1.0223495 0.8009662 1.3468990
#> [313] 0.7954000 1.0335348 0.9537581 0.8680955 0.7970334 0.9156945
#> [319] 0.8972355 0.8664653 0.8261422 0.9690331 0.8414026 1.0372701
#> [325] 0.8060715 0.9579017 1.0383451 1.0335348 1.0109306 0.9142022
#> [331] 0.9255135 0.9684420 1.0372701 0.9216199 0.8217287 0.7954000
#> [337] 0.7989606 1.0123554 0.9285543 0.9263597 0.9196405 0.9385895
#> [343] 0.8807888 0.9458628 0.8217287 0.9690331 0.7949935 0.9179396
#> [349] 0.9452232 0.9368858 0.8217287 0.9263597 1.0389982 0.9997047
#> [355] 1.0187595 0.9230120 0.9777110 0.8664653 0.8060715 0.9709256
#> [361] 0.9431400 0.8261422 0.8734958 0.8597203 0.8863608 0.9202695
#> [367] 0.9148701 0.9601266 0.9285543 1.0149425 0.8734958 0.9457977
#> [373] 1.0114148 0.9120695 1.0223495 0.9326362 0.9148701 0.9039897
#> [379] 0.9997047 1.0109306 0.8261422 0.8359769 1.0256796 0.9421412
#> [385] 0.8074042 1.0389311 0.9777110 1.0337789 1.0290609 0.9619671
#> [391] 0.8359769 0.7973727 1.0314277 0.9204738 0.8217287 0.9686647
#> [397] 0.9497401 0.8686921 0.9669477 0.9238641 0.9980374 0.8139015
#> [403] 0.8664653 0.9745660 0.9935538 0.8034038 1.0314277 0.9621551
#> [409] 1.0385178 0.9927136 1.0389982 0.8414026 0.9421412 0.7954000
#> [415] 1.0314277 0.9672928 0.9351989 0.8597203 1.0357373 0.8941787
#> [421] 0.7954000 0.9146474 0.9649475 0.9141026 1.0383451 0.9255135
#> [427] 0.8308910 0.9421412 0.9509768 1.0335348 0.9665021 0.8009662
#> [433] 0.7954000 0.8960631 0.7949611 0.8217287 1.0270456 0.9378192
#> [439] 0.9709256 1.0389311 1.0389982 0.9421412 0.8359769 -0.9673523
#> [445] 0.9165309 1.0388477 1.0143379 0.9927136 1.0357373 0.9421412
#> [451] 0.8883200 0.8074042 1.0228383 0.8308910 0.9196818 0.8176487
#> [457] 1.0187595 2.9050821 1.0178864 0.9537581 0.9136502 0.9154286
#> [463] 0.9102636 0.8217287 0.9509768 1.0372701 0.9799317 0.8104866
#> [469] 0.9385895 0.9141026 1.0306190 0.8104866 0.9459876 0.9617372
#> [475] 0.8857022 0.8471710 0.9457977 0.9370618 0.9497401 0.8734958
#> [481] 0.9421412 0.9890250 0.8764847 0.7984271 0.8810468 0.8104866
#> [487] 1.0256796 1.0270456 1.0160853 1.0248357 0.9579017 0.8734958
#> [493] 0.8597203 0.9421412 0.9709256 0.9120695 0.8261422 1.0358096
#> [499] 0.8532821 0.8308910 0.8734958 0.8734958 0.9039897 0.8261422
#> [505] 0.9385895 0.9853624 0.9285543 1.0062732 1.4322558 0.9497401
#> [511] 0.8359769 0.9691452 1.0389982 0.9927136 0.9277721 1.0109306
#> [517] 0.8664653 0.9285543 0.8009662 0.9599426 0.8176487 1.0374631
#> [523] 1.0306190 0.9457826 0.8785293 0.8664653 1.0374631 0.9709256
#> [529] 0.9619671 0.8941787 0.8883993 0.9285543 1.1679189 0.8308910
#> [535] 0.9636238 1.0062732 0.8471710 0.9368858 0.8471710 0.9156945
#> [541] 1.0372701 0.8022412 0.9352218 0.9636238 0.9698176 0.9290935
#> [547] 0.9680852 0.8734958 0.9684420 0.8682537 0.9659125 0.9997047
#> [553] 0.9141026 0.9997047 0.9484175 0.7989606 0.8471710 0.8001642
#> [559] 0.9890250 0.9512556 1.0270456 0.9698176 0.9659125 0.8807888
#> [565] 0.9537581 0.8217287 0.9509768 0.9154286 0.9509768 0.9617372
#> [571] 0.8001642 1.0278628 0.9690331 0.9927136 0.8359769 0.8992000
#> [577] 1.0187595 0.8034038 0.9534503 0.8664653 0.8960631 0.9997047
#> [583] 0.9216199 0.9890250 0.9102636 0.9214478 1.9910448 0.8046553
#> [589] -0.9793287 0.8217287 1.0389982 0.9665021 0.9202695 1.0024476
#> [595] 0.9535226 0.8703565 0.8664653 0.9632851 0.9263597 0.8597203
#> [601] 0.8471710 0.9368858 0.8104866 0.8807888 0.8664653 0.9320520
#> [607] 1.0306190 1.0123554 0.8785293 1.0067554 0.9458628 0.9167849
#> [613] 1.0385178 0.8471710 1.0228008 0.9039897 0.8074042 0.9727786
#> [619] 0.8022412 0.9285543 0.9579017 1.0223495 0.9777110 0.9684420
#> [625] 0.8034038 0.9617372 1.0374631 0.9039897 0.8217287 0.9844771
#> [631] 0.7984271 0.9263597 0.9662858 0.8734958 1.0228008 1.0385178
#> [637] 0.8074042 0.9452232 0.9890250 0.8217287 1.0388477 0.9997047
#> [643] 0.8034038 0.9141026 1.0306190 0.9233985 0.8139015 0.8764847
#> [649] 1.0358096 0.8863608 0.9457826 0.9853624 0.9141026 0.9431420
#> [655] 0.8139015 0.8261422 0.9352218 0.8308910 1.0278628 0.9621551
#> [661] 0.9120695 0.8176487 1.0389982 1.0374631 0.9665021 0.9579017
#> [667] 1.0372701 0.9558123 0.9698176 0.8074042 0.8359769 0.8686424
#> [673] 0.8034038 0.9665021 0.9698176 1.0256796 0.9844771 1.0337789
#> [679] 0.8046553 0.9263597 1.6233067 0.7984271 0.8532821 1.0314277
#> [685] 0.8261422 0.9698176 0.9890250 1.0389311 0.9277721 0.8139015
#> [691] 0.9621551 0.9698176 1.0256796 0.9196405 0.7970334 0.9698176
#> [697] 1.0024476 0.9351989 0.9649475 0.8022412 0.9154286 0.8001642
#> [703] 0.8414026 0.9698176 1.3702305 0.9535226 0.9684420 1.0389311
#> [709] 0.7952948 1.0389982 0.9534503 0.9632851 0.9669477 0.9665021
#> [715] 0.9997047 1.0389311 0.8359769 0.9145589 0.9214478 0.9285543
#> [721] 0.9196818 0.9997047 0.8217287 0.9351989 0.9844771 0.8471710
#> [727] 0.9165309 0.7954000 0.8883200 0.7970334 0.9255135 1.0066941
#> [733] 0.8217287 0.9535226 0.9039897 0.7954000 1.0306190 0.8022412
#> [739] 0.8532821 0.9558123 0.8176487 1.0372701 1.0314277 0.9142022
#> [745] 0.9686647 0.9536658 1.0389311 0.8686424 0.8532821 0.8664653
#> [751] 1.0187595 0.7984271 0.8471710 0.8597203 0.9142022 0.8807888
#> [757] 0.8972355 0.9632851 1.0024476 1.0114148 0.9352218 0.9559203
#> [763] 0.9600973 0.8863608 0.8471710 0.9277721 0.9202695 0.9691452
#> [769] 0.8308910 1.0187595 0.8074042 0.9039897 1.0024476 0.9650631
#> [775] 1.0223495 0.9458628 0.8786935 0.9338669 0.9069143 1.0344882
#> [781] 1.0256796 0.8001642 0.8359769 0.9156945 0.8686424 0.9927136
#> [787] 0.9580368 0.9621551 0.9167849 1.0314277 0.9142022 0.9927136
#> [793] 0.8883200 0.9431420 1.0389311 0.9688941 0.9318810 0.8807888
#> [799] 0.9777110 0.7989606 0.9579017 0.8308910 1.0306190 0.9204738
#> [805] 0.9165309 0.9352218 0.8729866 0.9497401 0.9659125 0.9146474
#> [811] 1.0187595 0.9458628 0.7970334 1.0223495 0.9202695 0.9202695
#> [817] 1.0149425 1.0389982 0.9290935 0.9847265 0.8807888 0.9204738
#> [823] 0.9579017 1.0357373 0.9120695 1.0223495 0.9579017 0.9632851
#> [829] 0.9277721 0.8261422 0.8734958 1.0178864 0.9305928 0.8009662
#> [835] 0.9680852 0.9709256 0.9368858 0.9202695 1.0256796 -5.9603587
#> [841] 0.8139015 1.0123554 0.9534503 0.8831501 0.9890250 1.0160853
#> [847] 0.9580368 1.0385178 1.0256796 1.0389982 0.8734958 0.8217287
#> [853] 0.9351989 0.8359769 0.9320520 0.9535226 1.0383451 0.9320520
#> [859] 1.0372701 0.9404746 0.9039897 0.9927136 0.9181207 1.0062732
#> [865] 0.9285543 0.8471710 0.9196405 0.8941787 0.9890250 0.9844771
#> [871] 0.9512556 0.9421412 1.0352834 1.0389982 0.9143324 0.9202695
#> [877] 0.9263597 0.9890250 1.0149425 0.9165309 1.0244508 0.9535226
#> [883] 0.9484175 0.9255135 0.8359769 0.9497401 0.9727048 0.9709256
#> [889] 0.9497401 0.9599426 0.9907617 0.8217287 0.9277721 0.9431400
#> [895] 0.9179396 1.0024476 0.9690331 1.0256796 1.0062732 0.8414026
#> [901] 0.9691924 1.0067554 0.9039897 0.9431420 0.9401591 0.8960631
#> [907] 0.9537581 0.9600973 0.9142022 0.9636238 0.9196405 1.0123554
#> [913] 1.0357373 1.0123554 0.8139015 1.0183793 0.7954000 1.0358096
#> [919] 0.8034038 0.7952948 0.9421412 1.0306190 0.8046553 0.9927136
#> [925] 0.9793343 0.7961896 0.9368858 0.8217287 0.7952948 0.9459876
#> [931] 1.0270456 0.8729866 0.9326362 0.8734958 1.0256796 0.9285543
#> [937] 0.9233985 1.0335348 0.9458628 0.9167849 0.7949935 0.9777110
#> [943] 0.9684420 1.0228008 0.9277721 1.0109306 1.0306190 0.8046553
#> [949] 0.7984271 0.9301534 1.0330942 1.0388317 0.9617011 0.9039897
#> [955] 0.8414026 0.9352218 0.9320520 0.9662858 0.8714905 0.8532821
#> [961] 0.8176487 0.8734958 1.0337789 0.9537581 0.7970334 0.8308910
#> [967] 0.8001642 0.8139015 0.7961896 1.0389311 0.9579017 1.0256796
#> [973] 1.0383451 0.9326362 0.9148701 0.9646903 0.9273995 0.9537581
#> [979] 1.0256796 1.0306209 0.9290935 0.9799317 0.9181207 0.7949611
#> [985] 1.0024476 0.8022412 0.8883993 0.9754082 0.9179396 0.9196405
#> [991] 0.9401591 0.8972355 1.0187595 0.9497401 1.0357373 0.8308910
#> [997] 0.8022412 0.9559203 0.9677921 0.9146474
#>
#> $adjusted
#> [1] 1.0374631 0.9777110 1.2571415 1.2220412 0.7536427 1.3780464
#> [7] 0.7066059 1.4099304 0.6553360 0.3223159 0.7115209 0.9599424
#> [13] 0.9484175 0.8247044 0.8150076 3.2242861 -2.1223211 2.8204772
#> [19] 1.1571153 1.7227980 0.9285543 1.5422271 0.9847265 3.8602526
#> [25] 0.4399878 0.9238790 0.5580921 0.7533248 0.5956282 0.9165309
#> [31] 0.9338669 1.1035686 1.1803252 1.0375467 1.6776930 0.7732017
#> [37] 1.4382219 1.3592958 0.9146474 2.2480000 1.6779256 0.7753162
#> [43] 1.4725170 0.8007045 0.7647362 1.2663201 0.7554057 1.2945675
#> [49] 0.6751594 0.7876451 0.9214478 1.7361911 0.5904681 1.1342678
#> [55] 0.7168505 1.4782628 0.7241897 0.3438092 0.6708488 1.4339762
#> [61] 1.1544425 0.5446100 0.9385895 0.8572640 1.6487470 0.4589698
#> [67] 0.7134072 1.8809492 1.4791116 0.5201017 1.7313862 0.9421412
#> [73] 1.8286648 1.9160737 1.3218276 0.4462164 0.9543538 1.7883574
#> [79] 0.8221137 0.4800366 0.9156945 1.2539541 1.0682457 0.6870794
#> [85] 1.0818524 0.7550665 1.2680901 2.1810888 0.9745666 0.9628526
#> [91] 0.4845962 0.9669477 1.3368435 0.9480913 1.0383451 1.2192602
#> [97] 0.8686921 0.6188566 2.8441263 1.9383849 1.3715926 1.8432398
#> [103] 0.9617372 0.9404746 0.9927136 1.2611504 0.9283557 0.3648278
#> [109] 1.0270456 0.3695109 2.0247108 0.9691452 1.2269185 0.9619671
#> [115] 1.7263493 1.4469359 2.4950935 1.1856894 0.6609138 0.9590133
#> [121] 0.8442134 1.1180813 1.3895396 0.9540321 1.5506684 0.3563388
#> [127] 1.0433298 1.1210040 1.0067554 0.9181207 1.2748426 1.0254119
#> [133] 0.6518074 1.0389982 3.8469489 0.9165309 1.2919185 0.9956257
#> [139] 0.8786382 1.3719043 1.4424438 0.8150076 0.7973727 0.9431420
#> [145] 0.9777110 1.2831433 0.7039421 0.6517467 0.8682537 1.4401460
#> [151] 0.6356335 0.4446271 0.7949611 1.2716775 1.2862538 2.0618525
#> [157] 2.8264235 0.8698611 0.7485281 0.9535226 0.7751511 1.2465310
#> [163] 0.9179396 0.6933440 0.7315561 1.3783719 0.7349488 0.4988821
#> [169] 1.8809492 0.7485281 1.3852415 1.1168028 0.8685705 0.8130359
#> [175] 0.9887108 1.7632800 1.1072287 1.1445097 0.9580368 0.9703270
#> [181] 0.6131212 0.9747735 0.4743472 1.2862538 1.1722053 0.8723742
#> [187] 0.7592452 1.0569466 1.1604753 1.6863945 0.8561120 0.8060715
#> [193] 1.5281393 0.8804236 0.1588446 0.9778046 0.7588101 1.2593162
#> [199] 1.1802710 0.9982809 0.8414026 0.3823249 0.7753540 1.0176449
#> [205] 1.5883418 0.9775188 3.4993815 1.4402110 1.2462214 1.7194406
#> [211] 1.4306372 0.8075637 1.0358096 0.4833698 0.9214478 1.2214400
#> [217] 1.1997344 1.5387802 1.2205715 1.0178864 1.3627478 0.9698176
#> [223] 0.4966432 0.8592938 0.8060715 0.7165516 1.0989166 1.0123554
#> [229] 1.3080586 2.0218612 0.9943887 1.2823163 1.8352958 0.4441600
#> [235] 1.8475544 0.9498873 1.4147130 1.8035833 0.6810395 0.5033777
#> [241] 1.9893210 1.3836325 0.5638794 0.8101913 0.9085640 1.2965876
#> [247] 0.7612069 0.9763442 0.9970692 1.1104215 0.6287613 0.6446423
#> [253] 0.9632851 0.7399104 0.6104630 1.1391038 1.4243832 1.2822476
#> [259] 1.4912831 0.8022412 0.6413114 1.7372489 0.6424159 0.9910595
#> [265] 1.0585108 0.4050957 1.0240721 0.9488316 0.5067053 0.7130230
#> [271] 0.9694064 0.8178796 2.2048463 0.8883200 0.8594525 1.1039000
#> [277] 1.5846668 0.5297348 1.0379552 0.6153413 0.8359769 0.9238641
#> [283] 1.4913750 0.9089084 0.6339845 0.9690331 3.8660083 1.4401460
#> [289] 1.6943421 0.5192589 0.7344966 1.4425517 0.9404746 0.9261450
#> [295] 0.9170588 1.0150530 1.8507026 1.2752535 0.9181207 1.3809831
#> [301] 0.6185147 0.9036170 0.4383684 0.6965297 0.9154286 2.4194802
#> [307] 0.5659346 1.5247596 0.7518357 2.2305807 0.8009662 1.7958653
#> [313] 0.7512111 1.0335348 0.9537581 1.3021433 1.6826262 1.6024654
#> [319] 0.4486177 0.9331165 0.9913707 1.4535496 1.5838166 0.7779526
#> [325] 1.3021155 1.7242231 0.3461150 0.9540321 0.7581979 2.2855056
#> [331] 1.8510269 0.9684420 1.0372701 1.8432398 1.2052020 0.6526359
#> [337] 0.7609148 0.6074132 1.8571086 1.2351463 0.6130937 0.4331951
#> [343] 0.7046311 0.9458628 1.3147658 1.9380661 1.1483240 0.7868054
#> [349] 1.1633516 1.4990174 0.7585188 0.7410878 2.4243291 0.8747416
#> [355] 3.0562786 0.4615060 1.7109943 1.2378076 1.1379833 1.4563884
#> [361] 1.4147099 0.8261422 0.5823305 0.8597203 0.8863608 0.8282426
#> [367] 0.7318961 0.7681012 1.8571086 1.6608150 1.9341693 3.7831908
#> [373] 1.0114148 0.4209552 1.0223495 0.4663181 0.9148701 1.6271815
#> [379] 0.5924176 0.7581979 1.5251857 1.3584624 2.5641990 1.1305694
#> [385] 0.6624855 1.2120863 1.2221388 1.5036784 1.0290609 0.9619671
#> [391] 0.5901013 1.3747804 2.5785692 1.3807107 0.5976208 1.4529970
#> [397] 0.4221067 0.8686921 0.9669477 0.9238641 1.6633957 1.3022423
#> [403] 0.8664653 0.9745660 1.9871076 1.2159626 1.0314277 2.3519348
#> [409] 1.3846904 0.9927136 0.9445438 0.9616029 0.3768565 0.7158600
#> [415] 1.2892846 0.7738342 0.9351989 0.7565539 1.7527862 0.8941787
#> [421] 1.0075067 0.4573237 1.2865966 0.9141026 1.2779632 1.3882702
#> [427] 1.0226350 0.6280941 0.6339845 0.3758308 0.5271829 0.9153899
#> [433] 0.9721556 1.0752757 0.9635893 0.8217287 1.2838070 0.6252128
#> [439] 0.9709256 1.4385200 0.5667263 1.6487470 1.2357919 -1.9347045
#> [445] 2.2913273 1.5582716 1.0143379 1.1912564 1.4796247 1.6487470
#> [451] 1.6721318 0.4749437 1.5342575 1.4125147 0.6131212 1.0512626
#> [457] 3.0562786 2.9050821 1.1309849 3.1791937 0.6091002 0.6865715
#> [463] 0.4551318 1.4193495 2.8529304 1.8152226 0.4199707 1.5091819
#> [469] 1.1732368 2.1329060 1.5855678 0.9725839 1.2613168 0.8014477
#> [475] 1.7714044 0.7701555 0.9457977 0.9370618 1.4246101 0.6551218
#> [481] 1.1776765 1.0789363 1.3147271 0.7185844 1.7620935 0.1350811
#> [487] 1.2308155 1.5800701 1.0160853 1.0248357 0.7982514 1.8389385
#> [493] 1.1961326 1.8842823 0.7767405 1.4924774 1.3218276 0.8286477
#> [499] 0.8532821 1.2463365 0.8319008 1.7469916 0.9515682 1.3769037
#> [505] 0.7508716 0.4926812 0.6554501 1.0062732 1.4322558 0.2374350
#> [511] 0.5573179 1.9382905 1.1874265 1.4890705 0.9277721 0.6739537
#> [517] 1.3330236 1.6249701 0.5950034 1.0970773 1.4717677 1.2968289
#> [523] 0.7594035 0.9457826 0.8785293 0.7581572 0.8299705 0.9709256
#> [529] 3.3668849 0.8941787 1.7767986 1.4591568 1.1679189 1.2282736
#> [535] 1.4454357 0.8050185 0.6589108 0.2162044 1.1295614 1.2209260
#> [541] 0.7779526 0.9766415 0.6234812 1.2848317 1.1083629 1.5484891
#> [547] 0.9680852 0.5516816 1.2912560 1.7365075 1.3798750 0.6664698
#> [553] 1.5235043 0.6664698 0.5690505 1.2471579 1.0668080 1.0463686
#> [559] 1.2362812 1.2683408 0.8558713 1.0910448 0.5519500 0.9608606
#> [565] 1.1921977 0.8765106 1.4264652 1.1442858 0.3803907 0.4808686
#> [571] 0.9001847 1.0278628 0.8305998 0.5672649 1.2075222 1.3488000
#> [577] 1.4262633 1.4139907 2.8603509 0.8664653 1.3440946 0.9997047
#> [583] 1.1520249 1.4835374 0.3034212 0.6142985 0.9955224 4.0232764
#> [589] -0.9793287 1.0347694 0.6493739 1.4497531 0.6401875 0.3759179
#> [595] 0.7946021 4.3517824 1.0727666 0.4281267 2.1615060 1.1125792
#> [601] 0.9966718 0.7753538 1.4503444 0.9227312 0.6601641 1.8641039
#> [607] 0.8588492 1.3498072 1.7570587 0.5752888 1.3242080 0.9167849
#> [613] 1.2462214 1.4632954 0.5578913 0.4017732 1.0765389 0.4863893
#> [619] 1.6044825 0.9285543 0.8210586 0.4381498 2.6072295 1.2912560
#> [625] 1.0225140 0.7693898 0.3772593 0.7231918 1.1504201 1.0938635
#> [631] 0.8710114 1.8527194 1.2078573 1.3102437 1.7046679 1.5577767
#> [637] 1.1303659 0.8270703 0.7192909 0.6723234 1.0388477 1.1107829
#> [643] 0.9494773 0.6855769 1.6031852 2.4623960 1.6859387 0.8764847
#> [649] 2.0716192 0.5909072 0.9457826 0.7390218 0.9141026 1.1789275
#> [655] 1.1162077 1.4319799 2.1821842 0.5934936 0.5139314 0.9621551
#> [661] 0.7600579 0.7267988 0.6233989 2.0749263 0.7248765 0.9579017
#> [667] 0.5186350 0.6372082 0.1686639 1.2748488 1.3932948 1.3029636
#> [673] 2.5708923 1.0738912 1.4778173 1.0256796 0.9844771 0.5907308
#> [679] 0.8470056 0.5052871 0.8116533 0.5666257 0.7584730 0.7501292
#> [685] 1.4269730 0.5968108 0.9890250 1.2467174 0.6185147 1.0231904
#> [691] 1.6494088 0.3636816 0.7692597 0.7357124 0.7970334 0.9698176
#> [697] 1.1138307 1.2469318 1.4474212 1.4440342 0.6865715 1.3093596
#> [703] 1.0096831 1.2930901 1.3702305 0.8974330 1.1621304 0.3777931
#> [709] 0.9872626 1.0389982 0.6356335 1.9265703 0.9669477 1.9330041
#> [715] 1.5995274 0.9590133 0.8851520 0.9145589 1.3821717 0.5714180
#> [721] 2.4524848 1.7889452 1.5777190 1.5586648 1.9689543 0.2946682
#> [727] 1.3093299 1.4317200 0.8883200 1.7711854 0.6941351 0.5033470
#> [733] 0.5800438 0.5804050 0.9039897 1.0748649 0.9369264 1.3477653
#> [739] 1.0038613 0.5213522 1.0063369 0.6223620 0.8595231 0.3656809
#> [745] 3.8746588 4.7683291 0.8311449 0.5790949 1.3652514 1.1552871
#> [751] 0.6112557 0.9124881 4.7749641 0.5373252 0.4986558 2.2019721
#> [757] 0.8972355 1.4449277 1.2530595 1.0114148 0.6234812 0.9559203
#> [763] 2.2402271 1.7727216 0.9036491 1.5462868 1.2992040 0.9691452
#> [769] 0.6996977 0.2546899 0.9688851 1.8079795 0.6014686 0.5514647
#> [775] 1.5903214 2.2070133 1.3180402 2.3346672 0.4534572 2.0689763
#> [781] 0.6837864 0.5091954 1.8391492 1.5261576 1.7372848 1.2846882
#> [787] 0.4790184 1.1545862 0.6111899 0.7934059 0.9142022 1.1030152
#> [793] 0.7315577 0.4715710 0.7991778 0.9688941 0.4659405 0.8130359
#> [799] 0.9777110 0.6214138 0.9579017 0.7270296 1.0306190 1.3807107
#> [805] 0.4999260 2.1821842 0.4364933 0.7123051 3.8636501 1.0162748
#> [811] 1.0187595 0.9458628 0.8316871 0.6815663 1.4461378 0.8494795
#> [817] 1.5224137 1.7001789 0.3378522 1.4770898 0.8807888 0.9204738
#> [823] 0.8514682 2.4167204 1.0640811 0.6815663 1.4368526 0.7224639
#> [829] 2.7833162 0.9294100 1.3438397 1.2214637 1.3958892 1.3349436
#> [835] 0.6453901 0.7281942 0.8197751 1.3561866 0.9467812 -11.9207174
#> [841] 1.2077247 1.0123554 1.2712671 1.3247251 0.4564731 1.0160853
#> [847] 0.9580368 0.8654315 0.4395770 1.7001789 0.9248779 1.1952417
#> [853] 0.3740795 1.1146359 1.1650650 0.7628180 0.5191725 0.7767100
#> [859] 1.3201619 1.8809492 1.6788381 0.6109007 1.2241610 0.8050185
#> [865] 0.8571271 0.9318882 0.5517843 2.2354467 0.9890250 0.7875817
#> [871] 1.2683408 1.4132117 2.0705668 1.0389982 0.9143324 1.1909370
#> [877] 0.9263597 0.3596454 1.0149425 1.8330618 3.0733523 1.0037080
#> [883] 1.5806959 1.2340179 0.8359769 0.6331600 1.4590572 1.2945675
#> [889] 0.6331600 0.7679541 0.9907617 1.3147658 1.3253887 1.4147099
#> [895] 0.6884547 1.5036715 1.9380661 0.7326283 1.2075278 0.7479134
#> [901] 0.6461283 0.8054043 1.7128227 1.5719033 0.7521273 0.9558006
#> [907] 0.5722549 1.2801298 0.6856517 0.7708990 0.6130937 1.3015998
#> [913] 1.0357373 0.5061777 1.6859387 0.5091897 0.6730308 1.1837824
#> [919] 1.3055312 0.5532486 2.8264235 0.7361565 0.7724691 1.0829603
#> [925] 0.9793343 0.9731207 1.1242630 0.8217287 1.3394440 1.8919752
#> [931] 0.6162274 0.8729866 0.2331591 0.8734958 0.7692597 1.2380724
#> [937] 0.9233985 1.0335348 0.8107396 1.8335698 1.3134676 0.6843977
#> [943] 0.4842210 0.9375674 1.3916581 1.7972099 0.9699944 0.6258430
#> [949] 0.6248560 5.1158438 1.0330942 2.0776634 0.9617011 0.7748484
#> [955] 1.1473671 1.2469624 1.8641039 0.5797715 0.8714905 1.8284617
#> [961] 1.1680696 0.7279132 0.8270231 2.1459558 1.3127610 0.9970692
#> [967] 1.0076142 1.0358746 1.1942845 1.0389311 2.5544046 0.6154078
#> [973] 0.5537840 2.1761512 1.1435877 0.6431269 0.4636997 1.6690767
#> [979] 0.8205437 2.0612418 2.3227337 0.3919727 0.4590604 1.1356588
#> [985] 0.8019581 1.2224628 1.0660792 0.9754082 0.6884547 0.6130937
#> [991] 0.9401591 2.2430886 0.7640696 0.7123051 1.2083602 1.3596398
#> [997] 1.2835860 0.6372802 1.5484673 0.5487884
#>