## ----setup, include = FALSE---------------------------------------------------
knitr::opts_chunk$set(
  collapse = TRUE,
  comment = "#>"
)

## ----message= FALSE, warning=FALSE--------------------------------------------
library(ceRNAnetsim)

## ---- eval=FALSE--------------------------------------------------------------
#  if (!requireNamespace("BiocManager", quietly = TRUE))
#      install.packages("BiocManager")
#  BiocManager::install("ceRNAnetsim")

## ---- warning= FALSE, message=FALSE-------------------------------------------
data("mirtarbasegene")
head(mirtarbasegene)

## -----------------------------------------------------------------------------
data("TCGA_E9_A1N5_normal")
head(TCGA_E9_A1N5_normal)

## -----------------------------------------------------------------------------
data("TCGA_E9_A1N5_tumor")
head(TCGA_E9_A1N5_tumor)

## -----------------------------------------------------------------------------
data("TCGA_E9_A1N5_mirnatumor")
head(TCGA_E9_A1N5_mirnatumor)

## -----------------------------------------------------------------------------
data("TCGA_E9_A1N5_mirnanormal")
head(TCGA_E9_A1N5_mirnanormal)

## -----------------------------------------------------------------------------
TCGA_E9_A1N5_mirnagene <- TCGA_E9_A1N5_mirnanormal %>%
  inner_join(mirtarbasegene, by= "miRNA") %>%
  inner_join(TCGA_E9_A1N5_normal, 
             by = c("Target"= "external_gene_name")) %>%
  select(Target, miRNA, total_read, gene_expression) %>%
  distinct() 

## ---- echo=FALSE--------------------------------------------------------------

TCGA_E9_A1N5_mirnagene%>%
  group_by(Target, miRNA)%>%
  count()%>%
  filter(n==2)

TCGA_E9_A1N5_mirnagene %>%    
  group_by(Target) %>%        
  mutate(gene_expression= max(gene_expression)) %>%
  distinct() %>%
  ungroup() -> TCGA_E9_A1N5_mirnagene


## -----------------------------------------------------------------------------
head(TCGA_E9_A1N5_mirnagene)

## -----------------------------------------------------------------------------
TCGA_E9_A1N5_mirnagene <- TCGA_E9_A1N5_mirnagene%>%
  filter(gene_expression > 10)

## ---- warning=FALSE, fig.height=5, fig.width=6, fig.align='center', warning=FALSE----

simulation_res_HIST <- TCGA_E9_A1N5_mirnagene %>% 
  priming_graph(competing_count = gene_expression, 
                miRNA_count = total_read) %>% 
  update_how(node_name = "HIST1H3H", how =30) %>% 
  simulate(5)

simulation_res_HIST%>%
  find_iteration(plot=TRUE)


## -----------------------------------------------------------------------------

simulation_res_HIST%>%
  as_tibble()%>%
  mutate(FC= count_current/initial_count)%>%
  arrange(desc(FC))

## ---- warning=FALSE, fig.height=5, fig.width=6, fig.align='center', warning=FALSE----
simulation_res_ACTB <- TCGA_E9_A1N5_mirnagene %>% 
  priming_graph(competing_count = gene_expression, 
                miRNA_count = total_read) %>% 
  update_how(node_name = "ACTB", how =1.87) %>% 
  simulate(5)

simulation_res_ACTB%>%
  find_iteration(plot=TRUE)

## -----------------------------------------------------------------------------

simulation_res_ACTB%>%
  as_tibble()%>%
  mutate(FC= count_current/initial_count)%>%
  arrange(desc(FC))

## ---- message=FALSE, warning=FALSE--------------------------------------------
data("huge_example")
head(huge_example)

## -----------------------------------------------------------------------------
filtered_example <- huge_example %>%
  add_count(competing) %>%
  filter(n > 5) %>%
  select(-n)

head(filtered_example)

## ---- fig.height=5, fig.width=6, fig.align='center', warning=FALSE------------
simulation_GAPDH <- filtered_example %>%
  priming_graph(competing_count = competing_counts, 
                miRNA_count = mirnaexpression_normal, 
                aff_factor = Energy) %>%
  update_how("GAPDH", 5) 

simulation_GAPDH%>%
  vis_graph(title = "Distribution of GAPDH gene node")

## ---- fig.height=5, fig.width=6, fig.align='center', warning=FALSE, fig.show='hide'----

simulation_GAPDH%>%
  simulate_vis(title = "GAPDH over expression in the real dataset", 3)

## ---- warning=FALSE-----------------------------------------------------------

entire_perturbation <- filtered_example%>%
  priming_graph(competing_count = competing_counts, miRNA_count = mirnaexpression_normal)%>%
  find_node_perturbation(how=5, cycle=3, fast = 15)%>%
  select(name, perturbation_efficiency, perturbed_count)
  

## ---- warning=FALSE-----------------------------------------------------------

entire_perturbation%>%
  filter(!is.na(perturbation_efficiency), !is.na(perturbed_count))%>%
  select(name, perturbation_efficiency, perturbed_count)

## ----sessioninfo--------------------------------------------------------------
sessionInfo()

