Last updated: 2019-11-18
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Knit directory: HHVtransmission/
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Rmd | 5ab3f97 | Bryan | 2019-11-10 | general statitisics update waddressing co-author comments |
html | 5ab3f97 | Bryan | 2019-11-10 | general statitisics update waddressing co-author comments |
html | e6ddfc5 | Bryan Mayer | 2019-07-09 | analysis through first-final draft |
Rmd | ccb8544 | Bryan Mayer | 2019-07-04 | updated analysis through exposure overview |
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Rmd | 94e6618 | Bryan Mayer | 2019-06-07 | update through transmission risk |
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html | 2eef601 | Bryan Mayer | 2019-04-19 | pre- removal of interpolation in exposure analysis |
Rmd | 9987890 | Bryan Mayer | 2019-04-12 | updated through exposure assessment |
html | 9987890 | Bryan Mayer | 2019-04-12 | updated through exposure assessment |
html | 37f0c94 | Bryan Mayer | 2019-04-08 | Build site. |
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Here, we calculate some of the initial (pre-model) results from the infant cohort and exposure characteristcs. - Demographics - Initial survial curves - Exposure assessment
library(survival)
library(tidyverse)
library(conflicted)
library(kableExtra)
library(cowplot)
conflict_prefer("filter", "dplyr")
theme_set(
theme_bw() +
theme(panel.grid.minor = element_blank(),
legend.position = "top")
)
source("code/plot_labels.R")
source("code/processing_functions.R")
exposure_data = read_csv("data/exposure_data.csv")
Parsed with column specification:
cols(
FamilyID = col_character(),
virus = col_character(),
infant_wks = col_double(),
infectious_1wk = col_double(),
final_infant_wk = col_double(),
infected = col_double(),
momhiv = col_character(),
final_exposure = col_double(),
interpolate_idpar = col_character(),
M = col_double(),
S = col_double(),
HH = col_double(),
obs_infected = col_double(),
final_wk = col_double(),
outcome_time = col_double(),
enrollment_age = col_double()
)
exposure_data_long = read_csv("data/exposure_data_long.csv")
Parsed with column specification:
cols(
FamilyID = col_character(),
virus = col_character(),
infant_wks = col_double(),
infectious_1wk = col_double(),
final_infant_wk = col_double(),
infected = col_double(),
momhiv = col_character(),
final_exposure = col_double(),
interpolate_idpar = col_character(),
obs_infected = col_double(),
final_wk = col_double(),
outcome_time = col_double(),
enrollment_age = col_double(),
idpar = col_character(),
count = col_double(),
interpolated = col_logical()
)
leg_plot = ggplot(data = exposure_data_long, aes(x = idpar, y = count, fill = factor(obs_infected))) +
geom_tile() +
scale_fill_manual("", values = infection_labels$colours, breaks = infection_labels$breaks,
labels = infection_labels$labels)
trans_legend = get_legend(leg_plot + theme(legend.position = "top"))
range_str = function(x, digits = 3) paste(round(range(x), digits), collapse = " - ")
IQR_range_str = function(x, digits = 3) paste(round(quantile(x, c(0.25, 0.75)), digits), collapse = " - ")
exposure_data %>%
select(FamilyID, enrollment_age) %>%
distinct() %>%
summarize(
N = n(),
enroll_median_age_days = median(enrollment_age),
IQR = paste(quantile(enrollment_age, c(0.25, 0.75)), collapse = ", "),
range_days = paste(range(enrollment_age), collapse = ", ")
) %>%
kable() %>% kable_styling(full_width = F)
N | enroll_median_age_days | IQR | range_days |
---|---|---|---|
32 | 2 | 1, 3 | 0, 9 |
exposure_data %>% select(FamilyID, momhiv) %>%
distinct() %>%
group_by(momhiv) %>%
summarize(N = n()) %>%
kable() %>% kable_styling(full_width = F)
momhiv | N |
---|---|
neg | 15 |
pos | 17 |
exposure_data %>%
group_by(virus, FamilyID) %>%
summarize(obs_infected = max(infectious_1wk),
is_infected = max(infected)) %>% group_by(virus) %>%
summarize(
total_infants = n_distinct(FamilyID),
total_infected = sum(is_infected),
total_outcome = sum(obs_infected)
) %>%
kable() %>%
kable_styling(full_width = F)
virus | total_infants | total_infected | total_outcome |
---|---|---|---|
CMV | 30 | 20 | 16 |
HHV-6 | 31 | 24 | 23 |
surv_data = exposure_data %>%
group_by(FamilyID, virus, momhiv, final_infant_wk) %>%
summarize(
infected = max(infected)
)
surv_fit = surv_data %>%
group_by(virus) %>%
nest() %>%
mutate(
surv_mod = map(data, ~survfit(Surv(final_infant_wk, infected) ~ 1, data = .)),
surv_mod_hiv = map(data, ~survfit(Surv(final_infant_wk, infected) ~ momhiv, data = .)),
logrank = map_dbl(data, ~coin::pvalue(coin::logrank_test(Surv(final_infant_wk, infected) ~ factor(momhiv),
data = ., distribution = "exact")))
) %>%
select(-data)
surv_fit %>%
select(virus, logrank) %>%
rename(`Mother HIV Log-rank` = logrank) %>%
kable() %>% kable_styling(full_width = F)
virus | Mother HIV Log-rank |
---|---|
CMV | 0.9708864 |
HHV-6 | 0.3649318 |
surv_res = pmap_df(surv_fit, function(virus, surv_mod, surv_mod_hiv, logrank){
broom::tidy(surv_mod) %>%
mutate(strata = "Pooled") %>%
bind_rows(broom::tidy(surv_mod_hiv)) %>%
mutate(
virus = virus,
momhiv = str_remove_all(strata, "momhiv=")
) %>%
bind_rows(crossing(virus = virus, time = -1e-12, estimate = 1, momhiv = c("Pooled", "neg", "pos")))
})
# NA censors recoded to 0 (occurs at time ~ 0)
surv_res %>%
arrange(virus, momhiv, time) %>%
mutate(n.censor = if_else(is.na(n.censor), 0, n.censor)) %>%
ungroup() %>%
mutate(virus = factor(virus, levels = c("HHV-6", "CMV"))) %>%
ggplot(aes(x = time, y = 1 - estimate, colour = momhiv)) +
geom_step() +
geom_point(aes(shape = n.censor > 0)) +
scale_shape_manual(guide = F, values = c(-1, 3)) +
scale_x_continuous("Weeks after infant birth", breaks = 0:10 * 10) +
scale_y_continuous("Proportion infected", expand = c(0.01, 0)) +
geom_vline(xintercept = 52, colour = "black", linetype = "dashed") +
scale_color_discrete("", breaks = c("neg", "pos", "Pooled"),
labels = c("Mother HIV-", "Mother HIV+", "Pooled")) +
facet_wrap(~virus) +
geom_text(data = mutate(ungroup(surv_fit), virus = factor(virus, levels = c("HHV-6", "CMV"))),
aes(label = str_c("p = ", round(logrank, 2))),
x = Inf, y = 0, colour = "black", vjust = -.2, hjust = 1.2) +
theme(legend.position = "top")
exposure_data_long %>%
subset(idpar != "HH") %>%
group_by(virus, idpar) %>%
summarize(
total = n(),
total_observed = total - sum(interpolated),
total_interpolate = stat_paste(sum(interpolated), 100*mean(interpolated), digits = 1)
) %>%
mutate(`Exposure source` = factor(idpar, levels = c("S", "M"),
labels = c("Secondary Children", "Mother"))) %>%
select(virus, `Exposure source`, everything(), -idpar) %>%
arrange(desc(virus), `Exposure source`) %>%
write_csv("output/supp_table1.csv") %>%
kable() %>%
kable_styling(full_width = F)
virus | Exposure source | total | total_observed | total_interpolate |
---|---|---|---|---|
HHV-6 | Secondary Children | 684 | 544 | 140.0 (20.5) |
HHV-6 | Mother | 684 | 646 | 38.0 (5.6) |
CMV | Secondary Children | 819 | 647 | 172.0 (21.0) |
CMV | Mother | 819 | 767 | 52.0 (6.3) |
exposure_data_summary = exposure_data_long %>%
mutate(
pos_count = count > 0
) %>%
subset(!interpolated) %>%
group_by(virus, FamilyID, obs_infected, idpar) %>%
mutate(
total_pos = sum(pos_count),
pct_pos = 100 * mean(pos_count)
) %>%
group_by(pct_pos, total_pos, add = T) %>%
summarise_at(vars(count), list(~n(), mean = mean, median = median, maximum = max)) %>%
rename(N = n)
plot_labels = exposure_data_summary %>%
gather(stat, estimate, mean, maximum, pct_pos) %>%
group_by(stat) %>%
summarize(min_lim = min(estimate), max_lim = ceiling(max(estimate))) %>%
left_join(tibble(stat = c("pct_pos", "mean", "maximum"),
out_lab = c("Percent~Positive", "Mean~Log[10]~VL", "Max.~Log[10]~VL"))) %>%
mutate(stat = factor(stat, levels = c("pct_pos", "mean", "maximum"))) %>%
arrange(stat) %>%
ungroup() %>%
mutate(letter_code = 1:3)
Joining, by = "stat"
pl_exposure = map(plot_labels$stat %>% levels(), function(s){
exposure_data_summary = exposure_data_summary %>%
ungroup() %>%
mutate(virus = factor(virus, levels = c("HHV-6", "CMV")))
tmp_theme = theme(
legend.position = "none",
axis.title = element_text(size = 10),
axis.text = element_text(size = 9)
)
pl_lab = subset(plot_labels, stat == s)
out_label = pl_lab$out_lab[1]
lower_limit = pl_lab$min_lim
upper_limit = pl_lab$max_lim
pl1 = exposure_data_summary %>%
gather(stat, estimate, mean, maximum, pct_pos) %>%
select(-median,-total_pos,-N) %>%
spread(idpar, estimate) %>%
filter(stat == s) %>%
ggplot(aes(
x = S,
y = M,
colour = factor(obs_infected)
)) +
geom_point() +
geom_abline() +
geom_point() +
scale_colour_manual(values = c("#4393C3", "#D6604D")) +
scale_y_continuous(parse(text = paste0("Mother~", out_label)),
limits = c(lower_limit, upper_limit)) +
scale_x_continuous(parse(text = paste0("Secondary~Children~", out_label)),
limits = c(lower_limit, upper_limit)) +
facet_wrap( ~ virus) +
tmp_theme
pl2 = exposure_data_summary %>%
ungroup() %>%
mutate(
obs_infected = factor(obs_infected),
idpar = fct_recode(
fct_rev(idpar),
"Secondary\nChildren" = "S",
"Mother" = "M",
"Household\nSum" = "HH"
)
) %>%
ggplot(aes_string(x = "idpar", y = s, colour = "obs_infected")) +
geom_boxplot() +
scale_colour_manual(values = c("#4393C3", "#D6604D")) +
geom_point(position = position_dodge(width = 0.75)) +
scale_y_continuous(parse(text = out_label), limits = c(lower_limit, upper_limit)) +
xlab(parse(text = c(""))) +
facet_wrap( ~ virus) +
tmp_theme + theme(axis.text.x = element_text(size = 7))
plot_grid(pl1, pl2, nrow = 1, labels = paste0("(",letters[c(pl_lab$letter_code, pl_lab$letter_code + 3)], ")"))
})
plot_grid(plot_grid(plotlist = pl_exposure, nrow = 3), trans_legend, nrow = 2, rel_heights = c(11, 1))
exposure_data_summary %>%
subset(idpar != "HH") %>%
group_by(virus, FamilyID, idpar) %>%
gather(outcome, value, pct_pos, mean, maximum) %>%
select(virus, FamilyID, idpar, outcome, value) %>%
spread(idpar, value) %>%
ungroup() %>%
dplyr::mutate(
fid = factor(FamilyID)
) %>%
group_by(virus, outcome) %>%
nest() %>%
mutate(
cor_test = map(data, ~cor.test(.x$M, .x$S), method = "Spearmen"),
cor_res = map(cor_test, broom::tidy)
) %>%
unnest(cor_res) %>%
mutate(
Endpoint = factor(outcome, levels = c("pct_pos", "mean", "maximum"),
labels = c("Pct. Positive", "Mean VL", "Maximum VL")),
Estimate = stat_paste(estimate, conf.low, conf.high, digits = 2),
p.value = round(p.value, 3)
) %>%
ungroup() %>%
select(virus, Endpoint, Estimate, p.value) %>%
arrange(desc(virus), Endpoint) %>%
write_csv("output/supp_table2.csv") %>%
kable(digits = 3) %>%
kable_styling(full_width = F) %>%
collapse_rows(1)
virus | Endpoint | Estimate | p.value |
---|---|---|---|
HHV-6 | Pct. Positive | 0.30 (-0.06, 0.59) | 0.095 |
Mean VL | 0.33 (-0.03, 0.61) | 0.074 | |
Maximum VL | 0.29 (-0.07, 0.59) | 0.111 | |
CMV | Pct. Positive | -0.04 (-0.40, 0.32) | 0.818 |
Mean VL | 0.06 (-0.31, 0.41) | 0.752 | |
Maximum VL | 0.06 (-0.31, 0.41) | 0.768 |
exposure_data_tests =
exposure_data_summary %>%
gather(stat, estimate, mean, maximum, pct_pos) %>%
group_by(virus, stat, idpar) %>%
mutate(obs_infected = factor(obs_infected)) %>%
summarize(
wilcox_pvalue = coin::pvalue(coin::wilcox_test(estimate ~ obs_infected, distribution = "exact"))
)
overall_summary = exposure_data_summary %>%
gather(stat, estimate, mean, maximum, pct_pos) %>%
group_by(virus, stat, idpar, obs_infected) %>%
summarize(
median = median(estimate)
) %>%
mutate(obs_infected = recode_factor(obs_infected, `1` = "Transmission", `0` = "No transmission", .ordered = T)) %>%
spread(obs_infected, median) %>%
mutate(Difference = `Transmission`-`No transmission`) %>%
left_join(exposure_data_tests, by = c("virus", "stat", "idpar"))
overall_summary %>%
ungroup() %>%
mutate(
wilcox_pvalue = as.character(round_away_0(wilcox_pvalue, 3, T)),
Endpoint = factor(
stat,
levels = c("pct_pos", "mean", "maximum"),
labels = c("Pct. Positive", "Mean VL", "Maximum VL")
),
`Exposure source` = factor(idpar, levels = c("S", "M", "HH"),
labels = c("Secondary child", "Mother", "Household Sum"))
) %>%
select(virus, Endpoint, `Exposure source`, everything(), -idpar, -stat) %>%
mutate_if(is.numeric, round, 2) %>%
arrange(desc(virus), Endpoint, `Exposure source`) %>%
write_csv("output/supp_table3.csv") %>%
kable() %>%
kable_styling(full_width = F) %>%
collapse_rows(columns = 1:2)
virus | Endpoint | Exposure source | Transmission | No transmission | Difference | wilcox_pvalue |
---|---|---|---|---|---|---|
HHV-6 | Pct. Positive | Secondary child | 100.00 | 94.50 | 5.50 | 0.003 |
Mother | 76.00 | 40.06 | 35.94 | 0.105 | ||
Household Sum | 100.00 | 98.91 | 1.09 | 0.008 | ||
Mean VL | Secondary child | 4.08 | 3.07 | 1.00 | 0.007 | |
Mother | 2.02 | 1.05 | 0.97 | 0.102 | ||
Household Sum | 4.12 | 3.41 | 0.71 | 0.006 | ||
Maximum VL | Secondary child | 4.63 | 3.68 | 0.95 | 0.020 | |
Mother | 3.34 | 3.00 | 0.34 | 0.147 | ||
Household Sum | 4.63 | 3.90 | 0.72 | 0.016 | ||
CMV | Pct. Positive | Secondary child | 100.00 | 94.05 | 5.95 | 0.230 |
Mother | 5.41 | 2.18 | 3.22 | 0.622 | ||
Household Sum | 100.00 | 95.30 | 4.70 | 0.249 | ||
Mean VL | Secondary child | 3.46 | 3.05 | 0.41 | 0.179 | |
Mother | 0.13 | 0.05 | 0.08 | 0.684 | ||
Household Sum | 3.47 | 3.05 | 0.42 | 0.179 | ||
Maximum VL | Secondary child | 4.42 | 4.34 | 0.08 | 0.377 | |
Mother | 1.11 | 2.49 | -1.38 | 0.653 | ||
Household Sum | 4.43 | 4.34 | 0.09 | 0.400 |
Household sum composition was determined and reported by taking the mean proportion over measurements within a household. The summary across the households uses median and IQR to match the box plot statistics.
hh_summary = exposure_data %>%
filter(HH > 0) %>%
mutate(
S_pctHH = if_else(HH == 0, 0, 100 * (10^S/10^HH)),
M_pctHH = if_else(HH == 0, 0, 100 * (10^M/10^HH))
) %>%
group_by(virus, FamilyID, obs_infected) %>%
summarise_at(vars(S_pctHH, M_pctHH), list(mean = mean, median = median))
hh_summary %>%
ungroup() %>%
select(-obs_infected) %>%
gather(stat, est, -virus, -FamilyID) %>%
group_by(virus, stat) %>%
summarize_if(is.double, list(mean = mean, median = median, IQR = IQR_range_str, range = range_str)) %>%
ungroup() %>%
mutate_if(is.double, round, digits = 2) %>%
filter(str_detect(stat, "mean")) %>%
mutate(
stat = substr(stat, 1, 1)
) %>%
rename(`Household member` = stat) %>%
rename_at(vars(-IQR), list(str_to_title)) %>%
kable(caption = "Percent household composition") %>% kable_styling(full_width = F)
Virus | Household Member | Mean | Median | IQR | Range |
---|---|---|---|---|---|
CMV | M | 7.27 | 0.32 | 0.094 - 5.426 | 0.004 - 66.421 |
CMV | S | 92.73 | 99.68 | 94.574 - 99.906 | 33.579 - 99.996 |
HHV-6 | M | 15.42 | 8.76 | 1.16 - 19.477 | 0.01 - 99.782 |
HHV-6 | S | 84.58 | 91.24 | 80.523 - 98.84 | 0.218 - 99.99 |
hh_summary %>%
ungroup() %>%
mutate(virus = factor(virus, levels = c("HHV-6", "CMV"))) %>%
ggplot(aes(x = virus, y = S_pctHH_mean)) +
geom_boxplot() +
geom_point(aes(colour = factor(obs_infected))) +
xlab("") +
scale_colour_manual("", values = infection_labels$colours, breaks = infection_labels$breaks,
labels = infection_labels$labels) +
ylab("Percent of household shedding attributable to secondary children")
In the sensitivity analysis, we’d like to assess the interpolation. All of the summary statistical analysis is limited to the observed exposures. Assuming the interpolation was unbiased, the precision in tests could still be artificially inflated without some correction. Because linear interpolation is used, the mean and maximum exposure estimates should be largely unaffected. However, the percent positive estimate may not be precise without a larger sample size.
exposure_interpolated_summary = exposure_data_long %>%
mutate(
pos_count = count > 0
) %>%
group_by(virus, FamilyID, obs_infected, idpar) %>%
mutate(
interpolated_pct = 100*mean(interpolated),
total_pos = sum(pos_count),
pct_pos = 100 * mean(pos_count)
) %>%
group_by(pct_pos, total_pos, interpolated_pct, add = T) %>%
dplyr::summarise_at(vars(count), list(~n(), mean = mean, median = median, maximum = max))
exposure_interpolated_summary %>%
ungroup() %>%
mutate(
idpar = fct_recode(fct_rev(idpar),
"Secondary\nChildren" = "S", "Mother" = "M", "Household\nSum" = "HH")
) %>%
ggplot(aes(x = idpar, y = interpolated_pct)) +
geom_boxplot() +
geom_point() +
xlab("") +
ylab("Percent of weekly exposures interpolated") +
facet_wrap(~virus)
exposure_interpolated_summary %>%
ungroup() %>%
subset(idpar != "HH") %>%
gather(stat, estimate, mean, maximum, pct_pos) %>%
mutate(
idpar = fct_recode(fct_rev(idpar),
"Secondary\nChildren" = "S", "Mother" = "M"),
stat = fct_recode(fct_rev(stat),
"% positive (weekly)" = "pct_pos", "Mean VL" = "mean", "Maximum VL" = "maximum"),
) %>%
ggplot(aes(x = interpolated_pct, y = estimate, colour = factor(obs_infected))) +
geom_point() +
ylab("") +
xlab("Percent of weekly exposures interpolated") +
facet_grid(stat ~ virus+idpar, scales = "free_y", switch = "y") +
scale_colour_manual("", values = infection_labels$colours, breaks = infection_labels$breaks,
labels = infection_labels$labels) +
theme(strip.placement = "outside")
sessionInfo()
R version 3.6.1 (2019-07-05)
Platform: x86_64-apple-darwin15.6.0 (64-bit)
Running under: macOS Catalina 10.15.1
Matrix products: default
BLAS: /Library/Frameworks/R.framework/Versions/3.6/Resources/lib/libRblas.0.dylib
LAPACK: /Library/Frameworks/R.framework/Versions/3.6/Resources/lib/libRlapack.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] cowplot_1.0.0 kableExtra_1.1.0 conflicted_1.0.4
[4] forcats_0.4.0 stringr_1.4.0 dplyr_0.8.3
[7] purrr_0.3.3 readr_1.3.1 tidyr_1.0.0
[10] tibble_2.1.3 ggplot2_3.2.1 tidyverse_1.2.1
[13] survival_2.44-1.1
loaded via a namespace (and not attached):
[1] httr_1.4.1 jsonlite_1.6 viridisLite_0.3.0
[4] splines_3.6.1 modelr_0.1.5 assertthat_0.2.1
[7] highr_0.8 stats4_3.6.1 selectr_0.4-1
[10] coin_1.3-1 cellranger_1.1.0 yaml_2.2.0
[13] pillar_1.4.2 backports_1.1.5 lattice_0.20-38
[16] glue_1.3.1 digest_0.6.22 rvest_0.3.5
[19] colorspace_1.4-1 sandwich_2.5-1 plyr_1.8.4
[22] htmltools_0.4.0 Matrix_1.2-17 pkgconfig_2.0.3
[25] broom_0.5.2 haven_2.1.1 mvtnorm_1.0-11
[28] scales_1.0.0 webshot_0.5.1 whisker_0.4
[31] git2r_0.26.1 generics_0.0.2 ellipsis_0.3.0
[34] TH.data_1.0-10 withr_2.1.2 lazyeval_0.2.2
[37] cli_1.1.0 magrittr_1.5 crayon_1.3.4
[40] readxl_1.3.1 memoise_1.1.0 evaluate_0.14
[43] fs_1.3.1 MASS_7.3-51.4 nlme_3.1-142
[46] xml2_1.2.2 tools_3.6.1 hms_0.5.1
[49] lifecycle_0.1.0 matrixStats_0.55.0 multcomp_1.4-10
[52] munsell_0.5.0 compiler_3.6.1 rlang_0.4.1
[55] grid_3.6.1 rstudioapi_0.10 labeling_0.3
[58] rmarkdown_1.17 codetools_0.2-16 gtable_0.3.0
[61] reshape2_1.4.3 R6_2.4.1 zoo_1.8-6
[64] lubridate_1.7.4 knitr_1.25 zeallot_0.1.0
[67] workflowr_1.4.0 libcoin_1.0-5 rprojroot_1.3-2
[70] modeltools_0.2-22 stringi_1.4.3 parallel_3.6.1
[73] Rcpp_1.0.3 vctrs_0.2.0 tidyselect_0.2.5
[76] xfun_0.10