Human Origins Array Global Results
jhmarcus
2019-02-15
Last updated: 2019-03-03
Checks: 6 0
Knit directory: drift-workflow/analysis/
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| Rmd | 7392ef2 | jhmarcus | 2019-03-03 | wflow_publish("analysis/*.Rmd") |
| Rmd | 90a0a02 | jhmarcus | 2019-02-28 | updated to autosomes and added manhatten plot |
| html | 90a0a02 | jhmarcus | 2019-02-28 | updated to autosomes and added manhatten plot |
| Rmd | d01c17c | jhmarcus | 2019-02-28 | added chrom exploration |
| Rmd | 5ee97ed | jhmarcus | 2019-02-27 | updating manhatten plots |
| Rmd | e1b4f85 | jhmarcus | 2019-02-25 | added snakemake rule |
| html | e1b4f85 | jhmarcus | 2019-02-25 | added snakemake rule |
| html | 38a461d | jhmarcus | 2019-02-24 | built all |
| html | b5aafbb | jhmarcus | 2019-02-24 | Build site. |
| Rmd | 63e7173 | jhmarcus | 2019-02-24 | expanded upon mean variance |
| html | 63e7173 | jhmarcus | 2019-02-24 | expanded upon mean variance |
| Rmd | 38b57c5 | jhmarcus | 2019-02-24 | simplified greedy flash global analysis |
| html | 38b57c5 | jhmarcus | 2019-02-24 | simplified greedy flash global analysis |
| Rmd | 403bc6b | jhmarcus | 2019-02-15 | added hide code blocks |
| html | 403bc6b | jhmarcus | 2019-02-15 | added hide code blocks |
| Rmd | b4749ac | jhmarcus | 2019-02-15 | fixed some typos |
| html | b4749ac | jhmarcus | 2019-02-15 | fixed some typos |
| Rmd | 7a2b6c7 | jhmarcus | 2019-02-15 | added backfit |
| html | 7a2b6c7 | jhmarcus | 2019-02-15 | added backfit |
| Rmd | f5ef1af | jhmarcus | 2019-02-15 | added workflows for human origins datasets |
| html | f5ef1af | jhmarcus | 2019-02-15 | added workflows for human origins datasets |
| Rmd | 4afc77e | jhmarcus | 2019-02-15 | init hoa global analysis |
This an analysis of the full Human Origins dataset which includes 2068 sampled from around the world. I filtered out rare variants with global minor allele frequency less than 5%, removed any variants with a missingness level greater than 1%, and removed any SNPs on the sex chromosomes. I then LD pruned the SNPs using standard parameters in plink, resulting in 165468 SNPs.
Imports
Lets import some needed packages:
library(ggplot2)
library(tidyr)
library(dplyr)
library(RColorBrewer)
library(biomaRt)
library(knitr)
source("../code/viz.R")FLASH-Greedy
Here is the snakemake rule I used for running flashier:
run:
R("""
# read the genotype matrix
Y = t(lfa:::read.bed('{params.bed}'))
# number of individuals
n = nrow(Y)
# run greedy flash
flash_fit = flashier::flashier(Y,
greedy.Kmax=20,
ash.param=list(method='fdr'),
prior.type=c('nonnegative', 'normal.mixture'),
var.type=2,
fixed.factors=flashier::ones.factor(1),
output.lvl=4,
verbose.lvl=2)
# save the rds
saveRDS(flash_fit, '{output.rds}')Lets first read the greedy flashier fit
# read the flash fit output by snakemake
flash_fit = readRDS("../output/flash_greedy/hoa_global_ld/HumanOriginsPublic2068_maf_geno_auto_ldprune.rds")
# read the snp meta data
bim_df = read.table("../data/datasets/hoa_global_ld/HumanOriginsPublic2068_maf_geno_auto_ldprune.bim", header=F)
colnames(bim_df) = c("chrom", "rsid", "cm", "pos", "a1", "a2")
# drift event loadings lfsr
l_lfsr_df = data.frame(flash_fit$lfsr[[1]])
colnames(l_lfsr_df) = 1:21
# drift event lfsr
delta_lfsr_df = data.frame(flash_fit$lfsr[[2]])
colnames(delta_lfsr_df) = 1:21
delta_lfsr_df$chrom = bim_df$chrom
delta_lfsr_df$pos = bim_df$pos
delta_lfsr_df$rsid = bim_df$rsid
# drift events
delta_df = as.data.frame(flash_fit$loadings$normalized.loadings[[2]])
colnames(delta_df) = 1:21
delta_df$chrom = bim_df$chrom
delta_df$pos = bim_df$pos
delta_df$rsid = bim_df$rsid
# number of drift events
K = ncol(flash_fit$loadings$normalized.loadings[[1]])
# number of individuals
n = nrow(flash_fit$loadings$normalized.loadings[[1]])
# number of SNPs
p = nrow(flash_fit$loadings$normalized.loadings[[2]])
print(K)[1] 21print(n)[1] 2068print(p)[1] 165468PVEs
Here is a plot of the proportion of variance (PVE) explained by each drift event:
p_pve = qplot(2:K, flash_fit$pve[2:K]) +
ylab("Proportion of Varaince Explained") +
xlab("K") +
theme_bw()
p_pve
print(flash_fit$pve) [1] 0.4758928191 0.0180430938 0.0221910986 0.0102953222 0.0025186497
[6] 0.0045329056 0.0015651404 0.0014220784 0.0011824621 0.0008636509
[11] 0.0007593062 0.0006714457 0.0005026230 0.0002140494 0.0001931981
[16] 0.0002269361 0.0001832276 0.0002904277 0.0002626722 0.0001573182
[21] 0.0001179608It looks like the PVE drops off at around 14 or so?
Fitted Mean and Variance
I setup the flashier run so it estimates a SNP specific precision term. Here is a histogram of fitted variances:
p_var = qplot(1/flash_fit$fit$est.tau) +
xlab("Estimated Variance") +
ylab("Count") +
theme_bw()
p_var
Lets now look the the fitted means:
mu = sqrt(flash_fit$loadings$scale.constant[1]) * delta_df$`1`
p_mu = qplot(mu) +
xlab("Estimated Mean") +
ylab("Count") +
theme_bw()
p_mu
These plots looks about reasonable as each of the SNP variances should roughly be interpreted as average heterozygosity \(\approx 2p(1-p)\)? The mean term should roughly be interpreted as the mean minor allele frequency at the SNP and thus we should see a quadratic relationship with the estimated variance:
d1 = flash_fit$loadings$scale.constant[1]
mv_df = data.frame(var=1/flash_fit$fit$est.tau, mu=mu, chrom=bim_df$chrom)
p_mv = ggplot(mv_df, aes(x=mu, y=var)) +
geom_point() +
xlab("Estimated Mean") + ylab("Estimated Variance") +
scale_alpha(guide = "none") +
stat_function(fun = function(x){return(2*x*(1-x))}, color="red") +
xlim(0, .5) +
theme_bw()
p_mv
Most of the SNPs have a mean-variance relationship expected under a simple Binomial model for the genotypes i.e. \(y_{ij} \sim Binomial(2, p_{ij})\). I wonder if there is anything “special” going on with the high variance SNP (will explore this later). I’m not sure why there is a sharp cuttof at .45.
Drift Event Distributions
Lets now plot the distribution of drift events:
# gather the data.frame for plotting
delta_gath_df = delta_df %>%
gather(K, value, -chrom, -pos, -rsid) %>%
filter(K!=1)
# plot the factors
K_ = K
p_de = ggplot(delta_gath_df, aes(x=value)) +
geom_histogram() +
facet_wrap(~factor(K, levels=2:K_), scales = "free") +
labs(fill="K") +
scale_x_continuous(breaks = scales::pretty_breaks(n = 3)) +
scale_y_continuous(breaks = scales::pretty_breaks(n = 3)) +
theme_bw()
p_de
We can see the lower PVE drift events tend to get sparser!
Drift Event Local False Sign Rates
Here histograms of the lfsrs for each drift event:
delta_lfsr_gath_df = delta_lfsr_df %>%
gather(K, value, -chrom, -pos, -rsid) %>%
filter(K %in% paste0(2:21))
p_lfsr = ggplot(delta_lfsr_gath_df, aes(x=value)) +
geom_histogram() +
facet_wrap(~factor(K, levels=2:K_), scales = "free") +
labs(fill="K") +
scale_x_continuous(breaks = scales::pretty_breaks(n = 3)) +
scale_y_continuous(breaks = scales::pretty_breaks(n = 3)) +
theme_bw() +
xlab("Local False Sign Rate")
p_lfsr`stat_bin()` using `bins = 30`. Pick better value with `binwidth`.
It is interesting to see the lower PVE factors (around 13 onwards) shift to having many SNPs with high uncertainity of the sign of the drift event.
Drift Event Loadings (2-11)
Lets now take a look at the drift event loadings. First we setup the data:
# read the meta data
meta_df = read.table("../data/meta/HumanOriginsPublic2068.meta", sep="\t", header=T)
# setup loadings data.frame
l_df = as.data.frame(flash_fit$loadings$normalized.loadings[[1]])
K = ncol(l_df)
l_df = cbind(l_df, meta_df)
# all unique pop labels
pops = unique(l_df$Simple.Population.ID)
# join with the meta data
l_df = l_df %>% arrange(Region, Simple.Population.ID) # sort by region then by population
l_df$ID = factor(l_df$ID, levels = l_df$ID) # make sure the ids are sorted
colnames(l_df)[1:K] = 1:K
head(l_df) 1 2 3 4 5 6
1 0.02198997 1.562440e-10 0.009748510 0.02224623 7.496723e-07 5.564681e-07
2 0.02198997 1.498617e-10 0.009740473 0.02269808 1.389697e-06 4.160829e-07
3 0.02198997 1.450794e-10 0.006494890 0.02497461 4.110090e-07 1.022280e-06
4 0.02198997 1.467553e-10 0.009433912 0.02314688 4.900230e-07 7.339584e-07
5 0.02198997 1.483937e-10 0.009868851 0.02290795 1.023726e-06 1.243865e-06
6 0.02198997 1.557400e-10 0.009509020 0.02230823 4.839558e-07 9.636279e-07
7 8 9 10 11
1 0.011864108 1.950983e-06 2.134680e-08 0.05518295 1.998480e-06
2 0.010896971 2.218510e-06 2.596953e-08 0.04932135 4.235657e-06
3 0.010882016 8.834097e-07 1.532842e-08 0.05498083 3.759938e-06
4 0.011011579 1.021461e-06 1.829201e-08 0.05974476 1.691153e-06
5 0.008335442 1.722933e-06 1.676397e-08 0.05778697 1.862318e-06
6 0.011669452 7.847559e-07 2.056824e-08 0.05614764 1.171816e-06
12 13 14 15 16
1 0.014841288 2.475559e-06 1.196299e-06 0.06257501 3.574080e-06
2 0.009671195 1.735489e-05 1.307078e-06 0.04815442 5.286249e-06
3 0.011501083 8.012301e-06 1.163721e-06 0.06577732 4.371689e-06
4 0.016477949 4.847320e-06 6.057587e-07 0.07252450 6.484941e-06
5 0.016029848 1.854048e-06 7.768784e-07 0.07805249 5.937048e-06
6 0.015462082 3.375407e-06 1.009148e-06 0.06144209 4.287258e-06
17 18 19 20 21
1 3.231384e-05 3.686193e-04 2.768013e-05 1.201701e-05 2.821169e-06
2 4.278782e-05 2.089317e-04 4.289490e-04 4.107142e-05 2.684191e-06
3 2.555584e-03 2.272919e-04 3.728350e-05 1.835738e-04 2.204598e-06
4 5.754635e-05 5.062869e-05 2.207929e-05 7.701641e-04 1.574267e-06
5 2.230132e-05 8.553066e-05 1.794721e-04 7.282639e-03 2.575973e-06
6 5.395636e-05 5.777995e-04 1.192646e-05 1.745599e-05 2.016293e-06
ID Simple.Population.ID Verbose.Population.ID Region Country
1 Algerian43A22 Algerian Algerian Africa Algeria
2 Algerian43A21 Algerian Algerian Africa Algeria
3 Algerian43A34 Algerian Algerian Africa Algeria
4 Algerian43A13 Algerian Algerian Africa Algeria
5 Algerian43A24 Algerian Algerian Africa Algeria
6 Algerian43A32 Algerian Algerian Africa Algeria
Latitude Longitude Samples Passed.QC Contributor
1 36.8 3 7 7 David Comas
2 36.8 3 7 7 David Comas
3 36.8 3 7 7 David Comas
4 36.8 3 7 7 David Comas
5 36.8 3 7 7 David Comas
6 36.8 3 7 7 David ComasIts hard to find a color scale that can sufficiently visualize all of the loadings in a single plot. Instead I just split the loadings up into two plots (K=2,…,11) and (K=12,…,21). Lets first visualize loadings 2 through 12:
# gather the data.frame for plotting
l_gath_df = l_df %>%
gather(K, value,
-ID,
-Verbose.Population.ID,
-Simple.Population.ID,
-Region, -Country,
-Latitude,
-Longitude,
-Samples,
-Passed.QC,
-Contributor) %>%
filter(K %in% paste0(2:11))
# Africa
africa_pops = get_pops(meta_df, "Africa")
p_africa = positive_structure_plot(gath_df=l_gath_df %>%
filter(Region == "Africa"),
colset="Set3",
facet_levels=africa_pops,
facet_grp="Simple.Population.ID",
label_size=5) +
ggtitle("Africa") +
theme(plot.title = element_text(size=6))
# America
america_pops = get_pops(meta_df, "America")
p_america = positive_structure_plot(gath_df=l_gath_df %>%
filter(Region == "America"),
colset="Set3",
facet_levels=america_pops,
facet_grp="Simple.Population.ID",
label_size=5) +
ggtitle("America") +
theme(plot.title = element_text(size=6))
# Central Asia Siberia
central_asia_siberia_pops = get_pops(meta_df, "CentralAsiaSiberia")
p_central_asia_siberia = positive_structure_plot(gath_df=l_gath_df %>%
filter(Region == "CentralAsiaSiberia"),
colset="Set3",
facet_levels=central_asia_siberia_pops,
facet_grp="Simple.Population.ID",
label_size=5) +
ggtitle("CentralAsiaSiberia") +
theme(plot.title = element_text(size=6))
# East Asia
east_asia_pops = get_pops(meta_df, "EastAsia")
p_east_asia = positive_structure_plot(gath_df=l_gath_df %>%
filter(Region == "EastAsia"),
colset="Set3",
facet_levels=east_asia_pops,
facet_grp="Simple.Population.ID",
label_size=5) +
ggtitle("EastAsia") +
theme(plot.title = element_text(size=6))
# South Asia
south_asia_pops = get_pops(meta_df, "SouthAsia")
p_south_asia= positive_structure_plot(gath_df=l_gath_df %>%
filter(Region == "SouthAsia"),
colset="Set3",
facet_levels=south_asia_pops,
facet_grp="Simple.Population.ID",
label_size=5) +
ggtitle("SouthAsia") +
theme(plot.title = element_text(size=6))
# West Eurasia
west_eurasia_pops = get_pops(meta_df, "WestEurasia")
p_west_eurasia = positive_structure_plot(gath_df=l_gath_df %>%
filter(Region == "WestEurasia"),
colset="Set3",
facet_levels=west_eurasia_pops,
facet_grp="Simple.Population.ID",
label_size=5) +
ggtitle("WestEurasia") +
theme(plot.title = element_text(size=6))
# Oceania
oceania_pops = get_pops(meta_df, "Oceania")
p_oceania = positive_structure_plot(gath_df=l_gath_df %>%
filter(Region == "Oceania"),
colset="Set3",
facet_levels=oceania_pops,
facet_grp="Simple.Population.ID",
label_size=5) +
ggtitle("Oceania") +
theme(plot.title = element_text(size=6))
# Global
p = cowplot::plot_grid(p_africa, p_west_eurasia, p_central_asia_siberia,
p_america, p_east_asia, p_south_asia, p_oceania,
rel_heights = c(1.2, 1.3, 1, 1, 1, 1, 1.1),
nrow = 7, align = "v")
p
Drift Event Loadings (12-21)
Lets now visualize loadings 12 to 21 (be careful: there is no connection to the colors in the last plot):
# gather the data.frame for plotting
l_gath_df = l_df %>%
gather(K, value,
-ID,
-Verbose.Population.ID,
-Simple.Population.ID,
-Region, -Country,
-Latitude,
-Longitude,
-Samples,
-Passed.QC,
-Contributor) %>%
filter(K %in% paste0(12:21))
# Africa
africa_pops = get_pops(meta_df, "Africa")
p_africa = positive_structure_plot(gath_df=l_gath_df %>%
filter(Region == "Africa"),
colset="Set3",
facet_levels=africa_pops,
facet_grp="Simple.Population.ID",
label_size=5) +
ggtitle("Africa") +
theme(plot.title = element_text(size=6))
# America
america_pops = get_pops(meta_df, "America")
p_america = positive_structure_plot(gath_df=l_gath_df %>%
filter(Region == "America"),
colset="Set3",
facet_levels=america_pops,
facet_grp="Simple.Population.ID",
label_size=5) +
ggtitle("America") +
theme(plot.title = element_text(size=6))
# Central Asia Siberia
central_asia_siberia_pops = get_pops(meta_df, "CentralAsiaSiberia")
p_central_asia_siberia = positive_structure_plot(gath_df=l_gath_df %>%
filter(Region == "CentralAsiaSiberia"),
colset="Set3",
facet_levels=central_asia_siberia_pops,
facet_grp="Simple.Population.ID",
label_size=5) +
ggtitle("CentralAsiaSiberia") +
theme(plot.title = element_text(size=6))
# East Asia
east_asia_pops = get_pops(meta_df, "EastAsia")
p_east_asia = positive_structure_plot(gath_df=l_gath_df %>%
filter(Region == "EastAsia"),
colset="Set3",
facet_levels=east_asia_pops,
facet_grp="Simple.Population.ID",
label_size=5) +
ggtitle("EastAsia") +
theme(plot.title = element_text(size=6))
# South Asia
south_asia_pops = get_pops(meta_df, "SouthAsia")
p_south_asia= positive_structure_plot(gath_df=l_gath_df %>%
filter(Region == "SouthAsia"),
colset="Set3",
facet_levels=south_asia_pops,
facet_grp="Simple.Population.ID",
label_size=5) +
ggtitle("SouthAsia") +
theme(plot.title = element_text(size=6))
# West Eurasia
west_eurasia_pops = get_pops(meta_df, "WestEurasia")
p_west_eurasia = positive_structure_plot(gath_df=l_gath_df %>%
filter(Region == "WestEurasia"),
colset="Set3",
facet_levels=west_eurasia_pops,
facet_grp="Simple.Population.ID",
label_size=5) +
ggtitle("WestEurasia") +
theme(plot.title = element_text(size=6))
# Oceania
oceania_pops = get_pops(meta_df, "Oceania")
p_oceania = positive_structure_plot(gath_df=l_gath_df %>%
filter(Region == "Oceania"),
colset="Set3",
facet_levels=oceania_pops,
facet_grp="Simple.Population.ID",
label_size=5) +
ggtitle("Oceania") +
theme(plot.title = element_text(size=6))
# Global
p = cowplot::plot_grid(p_africa, p_west_eurasia, p_central_asia_siberia,
p_america, p_east_asia, p_south_asia, p_oceania,
rel_heights = c(1.2, 1.3, 1, 1, 1, 1, 1.1),
nrow = 7, align = "v")
p
Its kinda interesting to see that some populations have zero loading on later factors. Its also interesting to see a lot of population specific factors arising. This would be difficult to visualize see if using a single plot for all the factors.
Drift Event Loadings Local False Sign Rates
l_lfsr_gath_df = l_lfsr_df %>%
gather(K, value) %>%
filter(K %in% paste0(2:21))
p_lfsr = ggplot(l_lfsr_gath_df, aes(x=value)) +
geom_histogram() +
facet_wrap(~factor(K, levels=2:K_), scales = "free") +
labs(fill="K") +
scale_x_continuous(breaks = scales::pretty_breaks(n = 3)) +
scale_y_continuous(breaks = scales::pretty_breaks(n = 3)) +
theme_bw() +
xlab("Local False Sign Rate")
p_lfsr`stat_bin()` using `bins = 30`. Pick better value with `binwidth`.
Its very intersting to see that the lfsr seem very bi-model for the loadings for many of the drift events.
ADMIXTURE
Lets visualize ADMIXTURE with 9 factors which should roughly align to the first plot i.e. FLASH with 2,…,11 (be careful: there is no connection to the colors in the last plot):
l_df = read.table("../output/admixture/hoa_global_ld/HumanOriginsPublic2068_maf_geno_auto_ldprune.K9r1.Q", sep=" ", header=F)
K = ncol(l_df)
l_df = cbind(l_df, meta_df)
pops = unique(l_df$Simple.Population.ID) # all unique pop labels
l_df = l_df %>% arrange(Region, Simple.Population.ID) # sort by region then by population
l_df$ID = factor(l_df$ID, levels = l_df$ID) # make sure the ids are sorted
colnames(l_df)[1:K] = 1:K
# gather the data.frame for plotting
l_gath_df = l_df %>%
gather(K, value, -ID, -Verbose.Population.ID, -Simple.Population.ID,
-Region, -Country, -Latitude, -Longitude, -Samples,
-Passed.QC, -Contributor)
# Africa
africa_pops = get_pops(meta_df, "Africa")
p_africa = positive_structure_plot(gath_df=l_gath_df %>%
filter(Region == "Africa"),
colset="Set3",
facet_levels=africa_pops,
facet_grp="Simple.Population.ID",
label_size=5) +
ggtitle("Africa") +
theme(plot.title = element_text(size=6))
# America
america_pops = get_pops(meta_df, "America")
p_america = positive_structure_plot(gath_df=l_gath_df %>%
filter(Region == "America"),
colset="Set3",
facet_levels=america_pops,
facet_grp="Simple.Population.ID",
label_size=5) +
ggtitle("America") +
theme(plot.title = element_text(size=6))
# Central Asia Siberia
central_asia_siberia_pops = get_pops(meta_df, "CentralAsiaSiberia")
p_central_asia_siberia = positive_structure_plot(gath_df=l_gath_df %>%
filter(Region == "CentralAsiaSiberia"),
colset="Set3",
facet_levels=central_asia_siberia_pops,
facet_grp="Simple.Population.ID",
label_size=5) +
ggtitle("CentralAsiaSiberia") +
theme(plot.title = element_text(size=6))
# East Asia
east_asia_pops = get_pops(meta_df, "EastAsia")
p_east_asia = positive_structure_plot(gath_df=l_gath_df %>%
filter(Region == "EastAsia"),
colset="Set3",
facet_levels=east_asia_pops,
facet_grp="Simple.Population.ID",
label_size=5) +
ggtitle("EastAsia") +
theme(plot.title = element_text(size=6))
# South Asia
south_asia_pops = get_pops(meta_df, "SouthAsia")
p_south_asia= positive_structure_plot(gath_df=l_gath_df %>%
filter(Region == "SouthAsia"),
colset="Set3",
facet_levels=south_asia_pops,
facet_grp="Simple.Population.ID",
label_size=5) +
ggtitle("SouthAsia") +
theme(plot.title = element_text(size=6))
# West Eurasia
west_eurasia_pops = get_pops(meta_df, "WestEurasia")
p_west_eurasia = positive_structure_plot(gath_df=l_gath_df %>%
filter(Region == "WestEurasia"),
colset="Set3",
facet_levels=west_eurasia_pops,
facet_grp="Simple.Population.ID",
label_size=5) +
ggtitle("WestEurasia") +
theme(plot.title = element_text(size=6))
# Oceania
oceania_pops = get_pops(meta_df, "Oceania")
p_oceania = positive_structure_plot(gath_df=l_gath_df %>%
filter(Region == "Oceania"),
colset="Set3",
facet_levels=oceania_pops,
facet_grp="Simple.Population.ID",
label_size=5) +
ggtitle("Oceania") +
theme(plot.title = element_text(size=6))
# Global
p = cowplot::plot_grid(p_africa, p_west_eurasia, p_central_asia_siberia,
p_america, p_east_asia, p_south_asia, p_oceania,
rel_heights = c(1.2, 1.3, 1, 1, 1, 1, 1.1),
nrow = 7, align = "v")
p
| Version | Author | Date |
|---|---|---|
| 90a0a02 | jhmarcus | 2019-02-28 |
There is a lot that one can compare between the ADMIXTURE and FLASH results. A high level observation seems that the ADMIXTURE results look a bit more clustered i.e. the Americas and East Asia look like they are explained mostly by 1 or 2 factors whereas FLASH uses 3-4. Its hard to tell be it seems that this is true in many of the super regions … ADMIXTURE tends use fewer factors to explain population structure in each region, leading to a more clustered result?
Outlier SNPs
Lets take a closer look at the drift factors to see if they are clustering in particular regions of the genome. As a first pass I take the top 5% of SNPs weighted on each drift event (to be clear I ignore the sign of each SNP). I would like to use the lfsr here but I will return to later. I then made a Manhatten plot for each chromosome and factor:
manh_df = delta_lfsr_df %>%
group_by(chrom) %>%
summarise(chr_len=max(pos)) %>%
mutate(tot=cumsum(chr_len)-chr_len) %>%
dplyr::select(-chr_len) %>%
left_join(delta_lfsr_df, ., by=c("chrom"="chrom")) %>%
arrange(chrom, pos) %>%
mutate(BPcum=pos+tot)
manh_axis_df = manh_df %>%
group_by(chrom) %>%
summarize(center=(max(BPcum) + min(BPcum)) / 2)
manh_gath_df = manh_df %>% gather(K, value, -chrom, -pos, -rsid, -tot, -BPcum) %>%
filter(K %in% paste0(2:11)) %>%
filter(value < 1e-10) %>%
filter(chrom %in% 1:22)
p = ggplot(manh_gath_df, aes(x=BPcum, y=-log10(value))) +
geom_point(aes(color=as.factor(chrom)), alpha=.7, size=.5) +
scale_color_manual(values=rep(c("grey", "orange"), 22)) +
scale_x_continuous(label=manh_axis_df$chrom, breaks=manh_axis_df$center) +
scale_y_continuous(expand=c(0, 0)) +
theme_bw() +
theme(axis.title.x=element_blank(), axis.ticks.x=element_blank(),
panel.grid.major = element_blank(), panel.grid.minor = element_blank()) +
facet_grid(factor(K, levels=2:11)~., scales = "free") +
ylab("-log10(lfsr)") +
guides(alpha=F, color=F)
pWarning in FUN(X[[i]], ...): NaNs producedWarning: Removed 1344 rows containing missing values (geom_point).
| Version | Author | Date |
|---|---|---|
| 90a0a02 | jhmarcus | 2019-02-28 |
We can see there are some regions on the chromosomes that are peaky as well as some regions that have no “outliers” at all. I then took the top 5 outliers in each factor and annotated them with some functional information:
# SNP bioMart database
grch37_snp = useMart(biomart="ENSEMBL_MART_SNP",
host="grch37.ensembl.org",
path="/biomart/martservice",
dataset="hsapiens_snp")
# GENE bioMart database
grch37 = useMart(biomart="ENSEMBL_MART_ENSEMBL",
host="grch37.ensembl.org",
path="/biomart/martservice",
dataset="hsapiens_gene_ensembl")
# top rank SNPs per each drift event
delta_tophit_df = delta_df %>%
gather(K, value, -chrom, -pos, -rsid) %>%
filter(K %in% paste0(2:21)) %>%
group_by(K) %>%
top_n(5, value)
# SNP meta data
table1 = getBM(attributes=c("refsnp_id",
"chrom_start",
"minor_allele_freq",
"ensembl_gene_stable_id",
"consequence_type_tv",
"associated_gene"),
filters = "snp_filter",
values = delta_tophit_df$rsid,
mart = grch37_snp)
table1$ensembl_gene_id = table1$ensembl_gene_stable_id
# GENE meta data
table2 = getBM(attributes = c("ensembl_gene_id", "external_gene_name", "description"),
filters = "ensembl_gene_id",
values = table1$ensembl_gene_stable_id,
mart = grch37)
# annotation data
anno_df = table1 %>% left_join(table2, on="ensembl_gene_id") %>%
mutate(rsid=refsnp_id) %>%
inner_join(delta_tophit_df, on="rsid") Joining, by = "ensembl_gene_id"Joining, by = "rsid"Warning: Column `rsid` joining character vector and factor, coercing into
character vector# unique genes
print(unique(anno_df$external_gene_name)) [1] "CCNL2" "CRYZ" "SLC22A15" NA
[5] "RP11-280O1.2" "KIAA1614" "C1orf132" "CD34"
[9] "FRMD4A" "MPP7" "SGPL1" "CCSER2"
[13] "RBM20" "NAV2" "SLC22A10" "STT3A-AS1"
[17] "STT3A" "HOXC13-AS" "CNOT2" "RP11-114H23.1"
[21] "APPL2" "LINC00641" "HERC2" "RP11-109D20.1"
[25] "SORD" "RP11-266O8.1" "PRKCB" "PKD1L2"
[29] "RP11-1407O15.2" "CACNB1" "RP11-515E23.1" "RP11-1055B8.4"
[33] "LINC01119" "IL1R1" "RAB3GAP1" "ZRANB3"
[37] "ITGB6" "TLK1" "PARD3B" "SF3A1"
[41] "DRG1" "TEF" "KAT2B" "SEMA3F"
[45] "FRMD4B" "MYH15" "CRMP1" "EVC"
[49] "RP11-103J17.1" "RP11-696N14.1" "SLC45A2" "NDUFAF2"
[53] "CTB-35F21.1" "DPYSL3" "UNC5A" "FLOT1"
[57] "AKAP12" "TIAM2" "TMEM248" "SMKR1"
[61] "RP11-150O12.1" "SMARCA2" "GLIS3" "RCL1"
[65] "PTPN3" # formatted table
d = anno_df %>%
distinct(external_gene_name, .keep_all = T) %>%
dplyr::select(external_gene_name, K, rsid, consequence_type_tv) %>%
arrange(consequence_type_tv)
kable(d)| external_gene_name | K | rsid | consequence_type_tv |
|---|---|---|---|
| NA | 3 | rs6428891 | |
| CRYZ | 11 | rs10890141 | intron_variant |
| SLC22A15 | 16 | rs17035177 | intron_variant |
| KIAA1614 | 15 | rs7545466 | intron_variant |
| FRMD4A | 8 | rs201874034 | intron_variant |
| MPP7 | 4 | rs10826403 | intron_variant |
| SGPL1 | 8 | rs7083883 | intron_variant |
| CCSER2 | 21 | rs56347056 | intron_variant |
| RBM20 | 19 | rs11598929 | intron_variant |
| NAV2 | 3 | rs10741783 | intron_variant |
| CNOT2 | 7 | rs11178168 | intron_variant |
| HERC2 | 12 | rs7494942 | intron_variant |
| SORD | 5 | rs2470686 | intron_variant |
| PRKCB | 13 | rs4787651 | intron_variant |
| CACNB1 | 15 | rs16531 | intron_variant |
| LINC01119 | 13 | rs6713911 | intron_variant |
| IL1R1 | 13 | rs3755295 | intron_variant |
| RAB3GAP1 | 12 | rs6730157 | intron_variant |
| ITGB6 | 8 | rs12987602 | intron_variant |
| TLK1 | 11 | rs78813632 | intron_variant |
| PARD3B | 10 | rs1207425 | intron_variant |
| SF3A1 | 5 | rs5749071 | intron_variant |
| DRG1 | 16 | rs2273248 | intron_variant |
| TEF | 6 | rs9611566 | intron_variant |
| KAT2B | 14 | rs2929402 | intron_variant |
| SEMA3F | 9 | rs11717349 | intron_variant |
| FRMD4B | 13 | rs34266487 | intron_variant |
| MYH15 | 2 | rs6437783 | intron_variant |
| EVC | 9 | rs4689306 | intron_variant |
| SLC45A2 | 4 | rs185146 | intron_variant |
| NDUFAF2 | 11 | rs1841504 | intron_variant |
| DPYSL3 | 18 | rs17106725 | intron_variant |
| UNC5A | 3 | rs692713 | intron_variant |
| AKAP12 | 16 | rs17081009 | intron_variant |
| TIAM2 | 6 | rs6916552 | intron_variant |
| TMEM248 | 8 | rs10264873 | intron_variant |
| SMKR1 | 14 | rs11771549 | intron_variant |
| SMARCA2 | 20 | rs7035991 | intron_variant |
| GLIS3 | 14 | rs10974315 | intron_variant |
| RCL1 | 3 | rs172447 | intron_variant |
| PTPN3 | 18 | rs12336101 | intron_variant |
| CCNL2 | 4 | rs1240747 | NMD_transcript_variant |
| RP11-1407O15.2 | 10 | rs8066255 | NMD_transcript_variant |
| C1orf132 | 21 | rs2235767 | non_coding_transcript_exon_variant |
| LINC00641 | 6 | rs12184962 | non_coding_transcript_exon_variant |
| PKD1L2 | 19 | rs16954698 | non_coding_transcript_exon_variant |
| RP11-1055B8.4 | 5 | rs3744146 | non_coding_transcript_exon_variant |
| RP11-280O1.2 | 2 | rs4657449 | non_coding_transcript_variant |
| CD34 | 21 | rs3820521 | non_coding_transcript_variant |
| SLC22A10 | 13 | rs6591765 | non_coding_transcript_variant |
| STT3A-AS1 | 20 | rs503288 | non_coding_transcript_variant |
| HOXC13-AS | 5 | rs2366148 | non_coding_transcript_variant |
| RP11-114H23.1 | 14 | rs3847673 | non_coding_transcript_variant |
| RP11-109D20.1 | 5 | rs2470686 | non_coding_transcript_variant |
| RP11-266O8.1 | 4 | rs7163903 | non_coding_transcript_variant |
| RP11-515E23.1 | 5 | rs9908046 | non_coding_transcript_variant |
| ZRANB3 | 12 | rs6730157 | non_coding_transcript_variant |
| CRMP1 | 9 | rs4689306 | non_coding_transcript_variant |
| RP11-103J17.1 | 9 | rs11733992 | non_coding_transcript_variant |
| RP11-696N14.1 | 7 | rs1229966 | non_coding_transcript_variant |
| CTB-35F21.1 | 15 | rs10067965 | non_coding_transcript_variant |
| FLOT1 | 15 | rs3094127 | non_coding_transcript_variant |
| RP11-150O12.1 | 11 | rs2407278 | non_coding_transcript_variant |
| STT3A | 20 | rs503288 | splice_region_variant |
| APPL2 | 20 | rs12303948 | synonymous_variant |
rsids on https://popgen.uchicago.edu/ggv/ to get a sense of what kind of allele frequency distributions define each factor.
sessionInfo()R version 3.5.1 (2018-07-02)
Platform: x86_64-apple-darwin13.4.0 (64-bit)
Running under: macOS 10.14.2
Matrix products: default
BLAS/LAPACK: /Users/jhmarcus/miniconda3/lib/R/lib/libRblas.dylib
locale:
[1] en_US.UTF-8/en_US.UTF-8/en_US.UTF-8/C/en_US.UTF-8/en_US.UTF-8
attached base packages:
[1] stats graphics grDevices utils datasets methods base
other attached packages:
[1] knitr_1.21 biomaRt_2.38.0 RColorBrewer_1.1-2
[4] dplyr_0.8.0.1 tidyr_0.8.2 ggplot2_3.1.0
loaded via a namespace (and not attached):
[1] progress_1.2.0 tidyselect_0.2.5 xfun_0.4
[4] reshape2_1.4.3 purrr_0.3.0 colorspace_1.4-0
[7] htmltools_0.3.6 stats4_3.5.1 yaml_2.2.0
[10] blob_1.1.1 XML_3.98-1.12 rlang_0.3.1
[13] pillar_1.3.1 glue_1.3.0 withr_2.1.2
[16] DBI_1.0.0 BiocGenerics_0.28.0 bit64_0.9-7
[19] plyr_1.8.4 stringr_1.4.0 munsell_0.5.0
[22] gtable_0.2.0 workflowr_1.2.0 flashier_0.1.0
[25] evaluate_0.12 memoise_1.1.0 labeling_0.3
[28] Biobase_2.42.0 IRanges_2.16.0 curl_3.3
[31] parallel_3.5.1 AnnotationDbi_1.44.0 highr_0.7
[34] Rcpp_1.0.0 scales_1.0.0 backports_1.1.3
[37] S4Vectors_0.20.1 fs_1.2.6 bit_1.1-14
[40] hms_0.4.2 digest_0.6.18 stringi_1.2.4
[43] cowplot_0.9.4 grid_3.5.1 rprojroot_1.3-2
[46] tools_3.5.1 bitops_1.0-6 magrittr_1.5
[49] lazyeval_0.2.1 RCurl_1.95-4.11 tibble_2.0.1
[52] RSQLite_2.1.1 crayon_1.3.4 whisker_0.3-2
[55] pkgconfig_2.0.2 prettyunits_1.0.2 assertthat_0.2.0
[58] rmarkdown_1.11 httr_1.4.0 R6_2.4.0
[61] git2r_0.23.0 compiler_3.5.1