Description Usage Arguments Value Author(s) References Examples
The Bayesian Hierarchical Model named Neoantigen-T cell interaction estimation (Netie) is to estimate the history of the immune pressure on the evolution of the tumor clones.
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input_one_patient |
a list with each data frame as the data for each patient. Each data frame consists 7 columns and each row is for one mutation. Please refer to https://github.com/tianshilu/Netie for more details. |
sigma_square |
hyperparameters for prior distributions. Please refer to https://github.com/tianshilu/Netie for more details. |
alpha |
hyperparameters for prior distributions. Please refer to https://github.com/tianshilu/Netie for more details. |
beta |
hyperparameters for prior distributions. Please refer to https://github.com/tianshilu/Netie for more details. |
sigma_p_sqr |
hyperparameters for prior distributions. Please refer to https://github.com/tianshilu/Netie for more details. |
sigma_a_sqr |
hyperparameters for prior distributions. Please refer to https://github.com/tianshilu/Netie for more details. |
max_iter |
the iterations of Markov chain Monte Carlo. |
multi_sample |
use True if one patient has more than one sample. |
The output is a list with the information of the anti-tumor selection pressure for each clone ac and for the whole tumor a.
Tianshi Lu
https://github.com/tianshilu/Netie
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##-- ==> Define data, use random,
##-- or do help(data=index) for the standard data sets.
data(input_data)
netie(input_data,sigma_square=100000,alpha=10,beta=2,
sigma_p_sqr=0.1,max_iter=1000,multi_sample=TRUE)
## The function is currently defined as
function (input_one_patient, sigma_square, alpha, beta, sigma_p_sqr,
sigma_a_sqr, max_iter, multi_sample = FALSE)
{
if (all(input_one_patient$neo_load[!is.na(input_one_patient$cluster_id)] ==
0)) {
return(NA)
}
input_one_patient = input_one_patient[!is.na(input_one_patient$cluster_id),
]
if (multi_sample == T) {
mutations = unlist(sapply(input_one_patient$mutation_id,
function(x) paste(strsplit(x, " ")[[1]][2], strsplit(x,
" ")[[1]][3])))
input_one_patient$neo_load = unlist(sapply(mutations,
function(x) max(input_one_patient[mutations == x,
"neo_load"])))
phi = "1"
clones = list()
clones[[id = "1"]] = mutations[paste(input_one_patient$sample_id,
input_one_patient$cluster_id) == paste(input_one_patient$sample_id,
input_one_patient$cluster_id)[1]]
for (each_clone in unique(paste(input_one_patient$sample_id,
input_one_patient$cluster_id))[-1]) {
mutations_one_clone = mutations[paste(input_one_patient$sample_id,
input_one_patient$cluster_id) == each_clone]
phi_tmp = unlist(sapply(1:length(clones), function(x) {
uniq_clone = clones[[x]]
shared_mutations = intersect(uniq_clone, mutations_one_clone)
if (length(shared_mutations)/length(uniq_clone) >
0.5 & length(shared_mutations)/length(mutations_one_clone) >
0.5) {
return(names(clones)[x])
}
}), use.names = FALSE)
if (!is.null(phi_tmp)) {
phi = c(phi, phi_tmp)
}
else {
phi_tmp = max(as.numeric(names(clones))) + 1
phi = c(phi, phi_tmp)
clones[[id = as.character(phi_tmp)]] = mutations_one_clone
}
}
names(phi) = unique(paste(input_one_patient$sample_id,
input_one_patient$cluster_id))
}
if (length(unique(input_one_patient$cluster_id)) > 1) {
if (is.null(sigma_a_sqr)) {
non_zero_neo_avg = sapply(unique(input_one_patient$cluster_id),
function(x) mean(input_one_patient[input_one_patient$cluster_id ==
x & input_one_patient$neo_load != 0, "neo_load"]))
non_zero_neo_avg[is.nan(non_zero_neo_avg)] = 0
sigma_a_sqr = sd(log(non_zero_neo_avg + 1))^2 * 10
if (sigma_a_sqr == 0) {
sigma_a_sqr = 1
}
}
}
else {
sigma_a_sqr = 1
}
if (sigma_square < 100 * sigma_a_sqr) {
print("sigma square should be much more larger than sigma a square!")
stop()
}
if (alpha <= beta) {
print("alpha should be larger than beta!")
stop()
}
if (multi_sample == T) {
max_vaf = unlist(sapply(mutations, function(x) max(input_one_patient[mutations ==
x, "variant_allele_frequency"])))
input_one_patient = input_one_patient[max_vaf > 0.05,
]
}
else {
input_one_patient = input_one_patient[input_one_patient$variant_allele_frequency >
0.05, ]
}
tmp = table(input_one_patient$cluster_id[input_one_patient$neo_load >
0])
tmp = names(tmp[tmp >= 1])
input_one_patient = input_one_patient[input_one_patient$cluster_id %in%
tmp, ]
tmp = table(input_one_patient$cluster_id)
tmp = names(tmp[tmp >= 2])
input_one_patient = input_one_patient[input_one_patient$cluster_id %in%
tmp, ]
if (dim(input_one_patient)[1] == 0) {
return(NA)
}
if (multi_sample == T) {
input_one_patient$phi = as.numeric(phi[paste(input_one_patient$sample_id,
input_one_patient$cluster_id)])
input_one_patient$cluster_id = as.numeric(factor(paste(input_one_patient$sample_id,
input_one_patient$cluster_id)))
phi_cluster = input_one_patient[, c("cluster_id", "phi")]
phi_cluster = phi_cluster[!duplicated(phi_cluster$cluster_id),
]
rownames(phi_cluster) = as.character(phi_cluster$cluster_id)
phi_cluster = phi_cluster[as.character(unique(input_one_patient$cluster_id)),
]
}
else {
input_one_patient$cluster_id = as.numeric(factor(input_one_patient$cluster_id))
}
input_one_patient[input_one_patient$neo_load > 150, "neo_load"] = 150
ac = bc = rep(0, length(unique(input_one_patient$cluster_id)))
pi = 0.5
a = 0
zck_list = list()
ac_list = list()
bc_list = list()
acp_rate_ac_list = list()
acp_rate_bc_list = list()
a_all = c()
pi_all = c()
for (iter in 1:max_iter) {
if (iter/1000 == round(iter/1000)) {
cat(paste("Iteration", iter, "\n"))
print(ac)
print(ac)
print(bc)
print(acp_rate_ac)
print(acp_rate_bc)
}
acp_rate_ac = rep(FALSE, length(unique(input_one_patient$cluster_id)))
acp_rate_bc = rep(FALSE, length(unique(input_one_patient$cluster_id)))
zck_df = input_one_patient[, c("mutation_id", "cluster_id")]
zck_df$zck = 1
if (multi_sample == T) {
for (p in 1:length(unique(input_one_patient$phi))) {
input_each_phi = input_one_patient[input_one_patient$phi ==
unique(input_one_patient$phi)[p], ]
for (c in unique(input_each_phi$cluster_id)) {
input_each_clone = input_each_phi[input_each_phi$cluster_id ==
c, ]
vck = input_each_clone$variant_allele_frequency
lambda = exp(ac[c] * vck + bc[c])
nck = input_each_clone$neo_load
r_tmp = pi * (nck == 0)/(pi * (nck == 0) +
(1 - pi) * dpois(nck, lambda, log = F))
r_tmp_deno = pi * (nck == 0) + (1 - pi) * dpois(nck,
lambda, log = F)
r_tmp[r_tmp_deno == 0] = 0
zck = 1 * (runif(length(nck), 0, 1) > r_tmp)
names(zck) = input_each_clone$mutation_id
zck_df$zck[zck_df$mutation_id %in% names(zck)] = zck
bc_prim = rnorm(1, bc[c], sqrt(sigma_p_sqr))
lambda_prim_b = exp(ac[c] * vck + bc_prim)
lambda = exp(ac[c] * vck + bc[c])
tmp_prim = sum((zck == 1) * dpois(nck, lambda_prim_b,
log = T))
tmp = sum((zck == 1) * dpois(nck, lambda, log = T))
llhr_b = exp(tmp_prim - bc_prim^2/(2 * sigma_square) -
tmp + bc[c]^2/(2 * sigma_square))
acceptance_function_b = min(1, llhr_b)
u = runif(1, 0, 1)
if (u <= acceptance_function_b) {
bc[c] = bc_prim
acp_rate_bc[c] = TRUE
}
}
input_each_phi$bc = bc[input_each_phi$cluster_id]
input_each_phi$ac = ac[c]
vck_phi = input_each_phi$variant_allele_frequency
lambda_phi = exp(input_each_phi$ac * vck_phi +
input_each_phi$bc)
nck_phi = input_each_phi$neo_load
zck_phi = zck_df[input_each_phi$mutation_id,
"zck"]
ac_prim = rnorm(1, ac[c], sqrt(sigma_p_sqr))
lambda_prim_a = exp(ac_prim * vck_phi + input_each_phi$bc)
tmp_prim = sum((zck_phi == 1) * dpois(nck_phi,
lambda_prim_a, log = T))
tmp = sum((zck_phi == 1) * dpois(nck_phi, lambda_phi,
log = T))
if (length(table(input_one_patient$cluster_id)) ==
1) {
llhr_a = exp(tmp_prim - ac_prim^2/(2 * sigma_square) -
tmp + ac[c]^2/(2 * sigma_square))
}
else {
llhr_a = exp(tmp_prim - (ac_prim - a)^2/(2 *
sigma_a_sqr) - tmp + (ac[c] - a)^2/(2 * sigma_a_sqr))
}
acceptance_function_a = min(1, llhr_a)
u = runif(1, 0, 1)
if (u <= acceptance_function_a) {
ac[phi_cluster$phi == unique(input_each_clone$phi)] = ac_prim
acp_rate_ac[c] = TRUE
}
}
pi = rbeta(1, alpha + sum((zck_df$zck == 0) * (input_one_patient$neo_load ==
0)), beta + sum(zck_df$zck == 1))
A = 1/sigma_square + length(unique(input_one_patient$phi))/sigma_a_sqr
B = sum(ac[!duplicated(phi_cluster$phi)])/sigma_a_sqr
a = rnorm(1, B/A, sqrt(1/A))
ac_list[[iter]] = ac
bc_list[[iter]] = bc
zck_list[[iter]] = zck_df$zck
acp_rate_ac_list[[iter]] = acp_rate_ac
acp_rate_bc_list[[iter]] = acp_rate_bc
a_all = c(a_all, a)
pi_all = c(pi_all, pi)
}
else {
for (c in 1:length(unique(input_one_patient$cluster_id))) {
input_each_clone = input_one_patient[input_one_patient$cluster_id ==
unique(input_one_patient$cluster_id)[c], ]
vck = input_each_clone$variant_allele_frequency
lambda = exp(ac[c] * vck + bc[c])
nck = input_each_clone$neo_load
r_tmp = pi * (nck == 0)/(pi * (nck == 0) + (1 -
pi) * dpois(nck, lambda, log = F))
r_tmp_deno = pi * (nck == 0) + (1 - pi) * dpois(nck,
lambda, log = F)
r_tmp[r_tmp_deno == 0] = 0
zck = 1 * (runif(length(nck), 0, 1) > r_tmp)
names(zck) = input_each_clone$mutation_id
zck_df$zck[zck_df$mutation_id %in% names(zck)] = zck
ac_prim = rnorm(1, ac[c], sqrt(sigma_p_sqr))
lambda_prim_a = exp(ac_prim * vck + bc[c])
tmp_prim = sum((zck == 1) * dpois(nck, lambda_prim_a,
log = T))
tmp = sum((zck == 1) * dpois(nck, lambda, log = T))
if (length(table(input_one_patient$cluster_id)) ==
1) {
llhr_a = exp(tmp_prim - ac_prim^2/(2 * sigma_square) -
tmp + ac[c]^2/(2 * sigma_square))
}
else {
llhr_a = exp(tmp_prim - (ac_prim - a)^2/(2 *
sigma_a_sqr) - tmp + (ac[c] - a)^2/(2 * sigma_a_sqr))
}
acceptance_function_a = min(1, llhr_a)
u = runif(1, 0, 1)
if (u <= acceptance_function_a) {
ac[c] = ac_prim
acp_rate_ac[c] = TRUE
}
bc_prim = rnorm(1, bc[c], sqrt(sigma_p_sqr))
lambda_prim_b = exp(ac[c] * vck + bc_prim)
lambda = exp(ac[c] * vck + bc[c])
tmp_prim = sum((zck == 1) * dpois(nck, lambda_prim_b,
log = T))
tmp = sum((zck == 1) * dpois(nck, lambda, log = T))
llhr_b = exp(tmp_prim - bc_prim^2/(2 * sigma_square) -
tmp + bc[c]^2/(2 * sigma_square))
acceptance_function_b = min(1, llhr_b)
u = runif(1, 0, 1)
if (u <= acceptance_function_b) {
bc[c] = bc_prim
acp_rate_bc[c] = TRUE
}
}
pi = rbeta(1, alpha + sum((zck_df$zck == 0) * (input_one_patient$neo_load ==
0)), beta + sum(zck_df$zck == 1))
A = 1/sigma_square + length(unique(input_one_patient$cluster_id))/sigma_a_sqr
B = sum(ac)/sigma_a_sqr
a = rnorm(1, B/A, sqrt(1/A))
ac_list[[iter]] = ac
bc_list[[iter]] = bc
zck_list[[iter]] = zck_df$zck
acp_rate_ac_list[[iter]] = acp_rate_ac
acp_rate_bc_list[[iter]] = acp_rate_bc
a_all = c(a_all, a)
pi_all = c(pi_all, pi)
}
}
keep = round(max_iter/2):max_iter
ac_final = Reduce("+", ac_list[keep])/length(keep)
bc_final = Reduce("+", bc_list[keep])/length(keep)
zck_df_final = round(Reduce("+", zck_list[keep])/length(keep))
names(zck_df_final) = zck_df$mutation_id
ac_rate = Reduce("+", acp_rate_ac_list[keep])/length(keep)
bc_rate = Reduce("+", acp_rate_bc_list[keep])/length(keep)
a_final = mean(a_all[keep])
pi_final = mean(pi_all[keep])
if (multi_sample == TRUE) {
final_parameters = list(zck = data.frame(zck_df_final),
ac = ac_final, bc = bc_final, acp_rate_ac = ac_rate,
a = a_final, acp_rate_bc = bc_rate, pi = pi_final,
phi_cluster = phi_cluster)
}
else {
final_parameters = list(zck = data.frame(zck_df_final),
ac = ac_final, bc = bc_final, acp_rate_ac = ac_rate,
a = a_final, acp_rate_bc = bc_rate, pi = pi_final)
}
all_parameters = list(zck = zck_list, ac = ac_list, bc = bc_list,
a = a_all, pi = pi_all)
result = list(all_parameters = all_parameters, final_parameters = final_parameters)
return(result)
}
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