GSSTDA Vignette: Gene Structure Survival using Topological Data Analysis

This vignette represents an introduction to the use of the package G-SS-TDA.

library(GSSTDA)

Loading data:

See GSSTDA documentation for further information.

data("full_data")
data("survival_time")
data("survival_event")
data("case_tag")

Declare the necessary parameters of the GSSTDA object.

The gen_select_type parameter is used to choose the option on how to select the genes to be used in the mapper. Choose between “Abs” and “Top_Bot”. The percent_gen_select parameter is the percentage of genes to be selected to be used in mapper.

# Gene selection information
gen_select_type <- "Top_Bot"
percent_gen_select <- 10 # Percentage of genes to be selected

For the mapper, it is necessary to know the number of intervals into which the values of the filter functions will be divided and the overlap between them (). Default are 5 and 40 respectively. It is also necessary to choose the type of distance to be used for clustering within each interval (choose between correlation (“correlation”), default, and euclidean (“euclidean”)) and the clustering type (choose between “hierarchical”, default, and “PAM” (“partition around medoids”) options).

For hierarchical clustering only, you will be asked by the console to choose the mode in which the number of clusters will be chosen (choose between “silhouette”, default, and “standard”). If you use the package’s own data we recommend to use “silhouette”. If the mode is “standard” you can indicate the number of bins to generate the histogram (, by default 10). If the clustering method is “PAM”, the default method will be “silhouette”. Also, if the clustering type is hierarchical you can choose the type of linkage criteria ( choose between “single”, “complete” and “average”).

#Mapper information
num_intervals <- 10
percent_overlap <- 40
distance_type <- "correlation"
clustering_type <- "hierarchical"
linkage_type <- "single" # only necessary if the type of clustering is hierarchical 
# num_bins_when_clustering <- 10 # only necessary if the type of clustering is hierarchical 
                                 # and the optimal_clustering_mode is "standard"
                                 # (this is not the case)

The package allows the various steps required for GSSTDA to be performed separately or together in one function.

OPTION #1 (the three blocks of the G-SS-TDA process are in separate function):

First step of the process: dsga.

This analysis, developed by Nicolau et al. is independent of the rest of the process and can be used with the data for further analysis other than mapper. It allows the calculation of the “disease component” which consists of, through linear models, eliminating the part of the data that is considered normal or healthy and keeping only the component that is due to the disease.

dsga_object <- dsga(full_data, survival_time, survival_event, case_tag)
#> Are the columns of the data set the patient and the rows the genes?: yes/no
#> 0  missing values and NaN's are omitted in the genes (rows)
#> What is the tag of the healthy patient (value in the case_tag)? (NT or T): 
#> [1] "The case tag is ' NT ' by default"
#> 
#> BLOCK I: The pre-process dsga is started
#> 
#> BLOCK I: The pre-process dsga is finished

Second step of the process: Select the genes within the dsga object created in the previous step and calcute the values of the filtering functions.

After performing a survival analysis of each gene, this function selects the genes to be used in the mapper according to both their variability within the database and their relationship with survival. Subsequently, with the genes selected, the values of the filtering functions are calculated for each patient. The filter function allows summarizing each vector of each individual into a single data point. This function takes into account the survival associated with each gene.

gene_selection_object <- gene_selection(dsga_object, gen_select_type, percent_gen_select)
#> [1] "dsga_object"
#> 
#> BLOCK II: The gene selection is started
#> Calculating the matrix of Zcox
#>   |                                                                              |                                                                      |   0%  |                                                                              |                                                                      |   1%  |                                                                              |=                                                                     |   1%  |                                                                              |=                                                                     |   2%  |                                                                              |==                                                                    |   2%  |                                                                              |==                                                                    |   3%  |                                                                              |==                                                                    |   4%  |                                                                              |===                                                                   |   4%  |                                                                              |===                                                                   |   5%  |                                                                              |====                                                                  |   5%  |                                                                              |====                                                                  |   6%  |                                                                              |=====                                                                 |   6%  |                                                                              |=====                                                                 |   7%  |                                                                              |=====                                                                 |   8%  |                                                                              |======                                                                |   8%  |                                                                              |======                                                                |   9%  |                                                                              |=======                                                               |   9%  |                                                                              |=======                                                               |  10%  |                                                                              |=======                                                               |  11%  |                                                                              |========                                                              |  11%  |                                                                              |========                                                              |  12%  |                                                                              |=========                                                             |  12%  |                                                                              |=========                                                             |  13%  |                                                                              |=========                                                             |  14%  |                                                                              |==========                                                            |  14%  |                                                                              |==========                                                            |  15%  |                                                                              |===========                                                           |  15%  |                                                                              |===========                                                           |  16%  |                                                                              |============                                                          |  16%  |                                                                              |============                                                          |  17%  |                                                                              |============                                                          |  18%  |                                                                              |=============                                                         |  18%  |                                                                              |=============                                                         |  19%  |                                                                              |==============                                                        |  19%  |                                                                              |==============                                                        |  20%  |                                                                              |==============                                                        |  21%  |                                                                              |===============                                                       |  21%  |                                                                              |===============                                                       |  22%  |                                                                              |================                                                      |  22%  |                                                                              |================                                                      |  23%  |                                                                              |================                                                      |  24%  |                                                                              |=================                                                     |  24%  |                                                                              |=================                                                     |  25%  |                                                                              |==================                                                    |  25%  |                                                                              |==================                                                    |  26%  |                                                                              |===================                                                   |  26%  |                                                                              |===================                                                   |  27%  |                                                                              |===================                                                   |  28%  |                                                                              |====================                                                  |  28%  |                                                                              |====================                                                  |  29%  |                                                                              |=====================                                                 |  29%  |                                                                              |=====================                                                 |  30%  |                                                                              |=====================                                                 |  31%  |                                                                              |======================                                                |  31%  |                                                                              |======================                                                |  32%  |                                                                              |=======================                                               |  32%  |                                                                              |=======================                                               |  33%  |                                                                              |=======================                                               |  34%  |                                                                              |========================                                              |  34%  |                                                                              |========================                                              |  35%  |                                                                              |=========================                                             |  35%  |                                                                              |=========================                                             |  36%  |                                                                              |==========================                                            |  36%  |                                                                              |==========================                                            |  37%  |                                                                              |==========================                                            |  38%  |                                                                              |===========================                                           |  38%  |                                                                              |===========================                                           |  39%  |                                                                              |============================                                          |  39%  |                                                                              |============================                                          |  40%  |                                                                              |============================                                          |  41%  |                                                                              |=============================                                         |  41%  |                                                                              |=============================                                         |  42%  |                                                                              |==============================                                        |  42%  |                                                                              |==============================                                        |  43%  |                                                                              |==============================                                        |  44%  |                                                                              |===============================                                       |  44%  |                                                                              |===============================                                       |  45%  |                                                                              |================================                                      |  45%  |                                                                              |================================                                      |  46%  |                                                                              |=================================                                     |  46%  |                                                                              |=================================                                     |  47%  |                                                                              |=================================                                     |  48%  |                                                                              |==================================                                    |  48%  |                                                                              |==================================                                    |  49%  |                                                                              |===================================                                   |  49%  |                                                                              |===================================                                   |  50%  |                                                                              |===================================                                   |  51%  |                                                                              |====================================                                  |  51%  |                                                                              |====================================                                  |  52%  |                                                                              |=====================================                                 |  52%  |                                                                              |=====================================                                 |  53%  |                                                                              |=====================================                                 |  54%  |                                                                              |======================================                                |  54%  |                                                                              |======================================                                |  55%  |                                                                              |=======================================                               |  55%  |                                                                              |=======================================                               |  56%  |                                                                              |========================================                              |  56%  |                                                                              |========================================                              |  57%  |                                                                              |========================================                              |  58%  |                                                                              |=========================================                             |  58%  |                                                                              |=========================================                             |  59%  |                                                                              |==========================================                            |  59%  |                                                                              |==========================================                            |  60%  |                                                                              |==========================================                            |  61%  |                                                                              |===========================================                           |  61%  |                                                                              |===========================================                           |  62%  |                                                                              |============================================                          |  62%  |                                                                              |============================================                          |  63%  |                                                                              |============================================                          |  64%  |                                                                              |=============================================                         |  64%  |                                                                              |=============================================                         |  65%  |                                                                              |==============================================                        |  65%  |                                                                              |==============================================                        |  66%  |                                                                              |===============================================                       |  66%  |                                                                              |===============================================                       |  67%  |                                                                              |===============================================                       |  68%  |                                                                              |================================================                      |  68%  |                                                                              |================================================                      |  69%  |                                                                              |=================================================                     |  69%  |                                                                              |=================================================                     |  70%  |                                                                              |=================================================                     |  71%  |                                                                              |==================================================                    |  71%  |                                                                              |==================================================                    |  72%  |                                                                              |===================================================                   |  72%  |                                                                              |===================================================                   |  73%  |                                                                              |===================================================                   |  74%  |                                                                              |====================================================                  |  74%  |                                                                              |====================================================                  |  75%  |                                                                              |=====================================================                 |  75%  |                                                                              |=====================================================                 |  76%  |                                                                              |======================================================                |  76%  |                                                                              |======================================================                |  77%  |                                                                              |======================================================                |  78%  |                                                                              |=======================================================               |  78%  |                                                                              |=======================================================               |  79%  |                                                                              |========================================================              |  79%  |                                                                              |========================================================              |  80%  |                                                                              |========================================================              |  81%  |                                                                              |=========================================================             |  81%  |                                                                              |=========================================================             |  82%  |                                                                              |==========================================================            |  82%  |                                                                              |==========================================================            |  83%  |                                                                              |==========================================================            |  84%  |                                                                              |===========================================================           |  84%  |                                                                              |===========================================================           |  85%  |                                                                              |============================================================          |  85%  |                                                                              |============================================================          |  86%  |                                                                              |=============================================================         |  86%  |                                                                              |=============================================================         |  87%  |                                                                              |=============================================================         |  88%  |                                                                              |==============================================================        |  88%  |                                                                              |==============================================================        |  89%  |                                                                              |===============================================================       |  89%  |                                                                              |===============================================================       |  90%  |                                                                              |===============================================================       |  91%  |                                                                              |================================================================      |  91%  |                                                                              |================================================================      |  92%  |                                                                              |=================================================================     |  92%  |                                                                              |=================================================================     |  93%  |                                                                              |=================================================================     |  94%  |                                                                              |==================================================================    |  94%  |                                                                              |==================================================================    |  95%  |                                                                              |===================================================================   |  95%  |                                                                              |===================================================================   |  96%  |                                                                              |====================================================================  |  96%  |                                                                              |====================================================================  |  97%  |                                                                              |====================================================================  |  98%  |                                                                              |===================================================================== |  98%  |                                                                              |===================================================================== |  99%  |                                                                              |======================================================================|  99%  |                                                                              |======================================================================| 100%
#> 
#> BLOCK II: The gene selection is finished

Another option to execute the second step of the process. Create a object “data_object” with the require information. This could be used when you do not want to apply dsga.

# Create data object
data_object <- list("full_data" = full_data, "survival_time" = survival_time,
                 "survival_event" = survival_event, "case_tag" = case_tag)
class(data_object) <- "data_object"


#Select gene from data object
gene_selection_object <- gene_selection(data_object, gen_select_type, percent_gen_select)
#> Are the columns of the data set the patient and the rows the genes?: yes/no
#> 0  missing values and NaN's are omitted in the genes (rows)
#> [1] "The case tag is ' NT ' by default"
#> 
#> BLOCK II: The gene selection is started
#> Calculating the matrix of Zcox
#>   |                                                                              |                                                                      |   0%  |                                                                              |                                                                      |   1%  |                                                                              |=                                                                     |   1%  |                                                                              |=                                                                     |   2%  |                                                                              |==                                                                    |   2%  |                                                                              |==                                                                    |   3%  |                                                                              |==                                                                    |   4%  |                                                                              |===                                                                   |   4%  |                                                                              |===                                                                   |   5%  |                                                                              |====                                                                  |   5%  |                                                                              |====                                                                  |   6%  |                                                                              |=====                                                                 |   6%  |                                                                              |=====                                                                 |   7%  |                                                                              |=====                                                                 |   8%  |                                                                              |======                                                                |   8%  |                                                                              |======                                                                |   9%  |                                                                              |=======                                                               |   9%  |                                                                              |=======                                                               |  10%  |                                                                              |=======                                                               |  11%  |                                                                              |========                                                              |  11%  |                                                                              |========                                                              |  12%  |                                                                              |=========                                                             |  12%  |                                                                              |=========                                                             |  13%  |                                                                              |=========                                                             |  14%  |                                                                              |==========                                                            |  14%  |                                                                              |==========                                                            |  15%  |                                                                              |===========                                                           |  15%  |                                                                              |===========                                                           |  16%  |                                                                              |============                                                          |  16%  |                                                                              |============                                                          |  17%  |                                                                              |============                                                          |  18%  |                                                                              |=============                                                         |  18%  |                                                                              |=============                                                         |  19%  |                                                                              |==============                                                        |  19%  |                                                                              |==============                                                        |  20%  |                                                                              |==============                                                        |  21%  |                                                                              |===============                                                       |  21%  |                                                                              |===============                                                       |  22%  |                                                                              |================                                                      |  22%  |                                                                              |================                                                      |  23%  |                                                                              |================                                                      |  24%  |                                                                              |=================                                                     |  24%  |                                                                              |=================                                                     |  25%  |                                                                              |==================                                                    |  25%  |                                                                              |==================                                                    |  26%  |                                                                              |===================                                                   |  26%  |                                                                              |===================                                                   |  27%  |                                                                              |===================                                                   |  28%  |                                                                              |====================                                                  |  28%  |                                                                              |====================                                                  |  29%  |                                                                              |=====================                                                 |  29%  |                                                                              |=====================                                                 |  30%  |                                                                              |=====================                                                 |  31%  |                                                                              |======================                                                |  31%  |                                                                              |======================                                                |  32%  |                                                                              |=======================                                               |  32%  |                                                                              |=======================                                               |  33%  |                                                                              |=======================                                               |  34%  |                                                                              |========================                                              |  34%  |                                                                              |========================                                              |  35%  |                                                                              |=========================                                             |  35%  |                                                                              |=========================                                             |  36%  |                                                                              |==========================                                            |  36%  |                                                                              |==========================                                            |  37%  |                                                                              |==========================                                            |  38%  |                                                                              |===========================                                           |  38%  |                                                                              |===========================                                           |  39%  |                                                                              |============================                                          |  39%  |                                                                              |============================                                          |  40%  |                                                                              |============================                                          |  41%  |                                                                              |=============================                                         |  41%  |                                                                              |=============================                                         |  42%  |                                                                              |==============================                                        |  42%  |                                                                              |==============================                                        |  43%  |                                                                              |==============================                                        |  44%  |                                                                              |===============================                                       |  44%  |                                                                              |===============================                                       |  45%  |                                                                              |================================                                      |  45%  |                                                                              |================================                                      |  46%  |                                                                              |=================================                                     |  46%  |                                                                              |=================================                                     |  47%  |                                                                              |=================================                                     |  48%  |                                                                              |==================================                                    |  48%  |                                                                              |==================================                                    |  49%  |                                                                              |===================================                                   |  49%  |                                                                              |===================================                                   |  50%  |                                                                              |===================================                                   |  51%  |                                                                              |====================================                                  |  51%  |                                                                              |====================================                                  |  52%  |                                                                              |=====================================                                 |  52%  |                                                                              |=====================================                                 |  53%  |                                                                              |=====================================                                 |  54%  |                                                                              |======================================                                |  54%  |                                                                              |======================================                                |  55%  |                                                                              |=======================================                               |  55%  |                                                                              |=======================================                               |  56%  |                                                                              |========================================                              |  56%  |                                                                              |========================================                              |  57%  |                                                                              |========================================                              |  58%  |                                                                              |=========================================                             |  58%  |                                                                              |=========================================                             |  59%  |                                                                              |==========================================                            |  59%  |                                                                              |==========================================                            |  60%  |                                                                              |==========================================                            |  61%  |                                                                              |===========================================                           |  61%  |                                                                              |===========================================                           |  62%  |                                                                              |============================================                          |  62%  |                                                                              |============================================                          |  63%  |                                                                              |============================================                          |  64%  |                                                                              |=============================================                         |  64%  |                                                                              |=============================================                         |  65%  |                                                                              |==============================================                        |  65%  |                                                                              |==============================================                        |  66%  |                                                                              |===============================================                       |  66%  |                                                                              |===============================================                       |  67%  |                                                                              |===============================================                       |  68%  |                                                                              |================================================                      |  68%  |                                                                              |================================================                      |  69%  |                                                                              |=================================================                     |  69%  |                                                                              |=================================================                     |  70%  |                                                                              |=================================================                     |  71%  |                                                                              |==================================================                    |  71%  |                                                                              |==================================================                    |  72%  |                                                                              |===================================================                   |  72%  |                                                                              |===================================================                   |  73%  |                                                                              |===================================================                   |  74%  |                                                                              |====================================================                  |  74%  |                                                                              |====================================================                  |  75%  |                                                                              |=====================================================                 |  75%  |                                                                              |=====================================================                 |  76%  |                                                                              |======================================================                |  76%  |                                                                              |======================================================                |  77%  |                                                                              |======================================================                |  78%  |                                                                              |=======================================================               |  78%  |                                                                              |=======================================================               |  79%  |                                                                              |========================================================              |  79%  |                                                                              |========================================================              |  80%  |                                                                              |========================================================              |  81%  |                                                                              |=========================================================             |  81%  |                                                                              |=========================================================             |  82%  |                                                                              |==========================================================            |  82%  |                                                                              |==========================================================            |  83%  |                                                                              |==========================================================            |  84%  |                                                                              |===========================================================           |  84%  |                                                                              |===========================================================           |  85%  |                                                                              |============================================================          |  85%  |                                                                              |============================================================          |  86%  |                                                                              |=============================================================         |  86%  |                                                                              |=============================================================         |  87%  |                                                                              |=============================================================         |  88%  |                                                                              |==============================================================        |  88%  |                                                                              |==============================================================        |  89%  |                                                                              |===============================================================       |  89%  |                                                                              |===============================================================       |  90%  |                                                                              |===============================================================       |  91%  |                                                                              |================================================================      |  91%  |                                                                              |================================================================      |  92%  |                                                                              |=================================================================     |  92%  |                                                                              |=================================================================     |  93%  |                                                                              |=================================================================     |  94%  |                                                                              |==================================================================    |  94%  |                                                                              |==================================================================    |  95%  |                                                                              |===================================================================   |  95%  |                                                                              |===================================================================   |  96%  |                                                                              |====================================================================  |  96%  |                                                                              |====================================================================  |  97%  |                                                                              |====================================================================  |  98%  |                                                                              |===================================================================== |  98%  |                                                                              |===================================================================== |  99%  |                                                                              |======================================================================|  99%  |                                                                              |======================================================================| 100%
#> 
#> BLOCK II: The gene selection is finished

Third step of the process: Create the mapper object with disease component matrix

with only the selected genes and the filter function obtained in the gene selection step.

Mapper condenses the information of high-dimensional datasets into a combinatory graph that is referred to as the skeleton of the dataset. To do so, it divides the dataset into different levels according to its value of the filtering function. These levels overlap each other. Within each level, an independent clustering is performed using the input matrix and the indicated distance type. Subsequently, clusters from different levels that share patients with each other are joined by a vertex.

This function is independent from the rest and could be used without having done dsga and gene selection

mapper_object <- mapper(data = gene_selection_object[["genes_disease_component"]], 
                        filter_values = gene_selection_object[["filter_values"]],
                        num_intervals = num_intervals,
                        percent_overlap = percent_overlap, distance_type = distance_type,
                        clustering_type = clustering_type,
                        linkage_type = linkage_type)
#> Are the columns of the data set the patient and the rows the genes?: yes/no
#> 0  missing values and NaN's are omitted in the genes (rows)
#> Choose one of the following optimal cluster number method: standard/silhouette:
#> The optimal clustering mode is 'silhouette '

Obtain information from the dsga block created in the previous step.

This function returns the 100 genes with the highest variability within the dataset and builds a heat map with them.

dsga_information <- results_dsga(dsga_object[["matrix_disease_component"]], case_tag)

print(dsga_information)
#>   [1] "CPB1"     "AGR3"     "BMPR1B"   "ANKRD30A" "CP"       "CEACAM6" 
#>   [7] "ADH1B"    "CXCL13"   "COL11A1"  "CHI3L1"   "CYP4Z1"   "AGR2"    
#>  [13] "CD36"     "CLIC6"    "CYP4X1"   "C19orf33" "AREG"     "APOD"    
#>  [19] "ADIPOQ"   "BEX1"     "AGTR1"    "CALML5"   "CLDN8"    "CYP4B1"  
#>  [25] "CRISP3"   "DACH1"    "CXCL14"   "AFF3"     "CYP2B7P"  "CAPN8"   
#>  [31] "COMP"     "CLSTN2"   "CCL19"    "CFB"      "CYP2T1P"  "CSTA"    
#>  [37] "AZGP1"    "CRISPLD1" "CLGN"     "ANXA3"    "CGA"      "CHGB"    
#>  [43] "CXCL9"    "AKR1C2"   "ACTG2"    "ALOX15B"  "AQP3"     "CLCA2"   
#>  [49] "COL2A1"   "CXCL11"   "CA12"     "C15orf48" "CA2"      "CYP4Z2P" 
#>  [55] "ASPN"     "AR"       "CHRDL1"   "AKR1C1"   "BBOX1"    "ABCA8"   
#>  [61] "CYP4F8"   "CT83"     "CXCL10"   "ABAT"     "CEACAM5"  "ADAMTS15"
#>  [67] "ANLN"     "CLDN1"    "CPE"      "DCLK1"    "CELSR1"   "COL10A1" 
#>  [73] "CFD"      "CNTNAP2"  "CLDN11"   "APOBEC3B" "ALDH3B2"  "C16orf54"
#>  [79] "CDO1"     "ANKRD30B" "COL14A1"  "ARHGAP36" "CECR2"    "BAMBI"   
#>  [85] "CCND1"    "ADGRG6"   "AKR1C3"   "ABCC13"   "C16orf89" "CCL8"    
#>  [91] "CNKSR3"   "DCD"      "CCL5"     "CEP55"    "CST6"     "ARNT2"   
#>  [97] "BEX5"     "COL4A5"   "CLEC3A"   "ARMT1"

Obtain information from the mapper object created in the G-SS-TDA process.

print(mapper_object)
#> $interval_data
#> $interval_data$Level_1
#> [1] 612.7152 627.1164
#> 
#> $interval_data$Level_2
#> [1] 621.3959 635.6971
#> 
#> $interval_data$Level_3
#> [1] 629.9766 644.2778
#> 
#> $interval_data$Level_4
#> [1] 638.5573 652.8585
#> 
#> $interval_data$Level_5
#> [1] 647.1381 661.4393
#> 
#> $interval_data$Level_6
#> [1] 655.7188 670.0200
#> 
#> $interval_data$Level_7
#> [1] 664.2995 678.6007
#> 
#> $interval_data$Level_8
#> [1] 672.8802 687.1814
#> 
#> $interval_data$Level_9
#> [1] 681.4609 695.7622
#> 
#> $interval_data$Level_10
#> [1] 690.0417 704.4429
#> 
#> 
#> $sample_in_level
#> $sample_in_level$Level_1
#> [1] "GSM1045193" "GSM1045217" "GSM1045302"
#> 
#> $sample_in_level$Level_2
#> [1] "GSM1045192" "GSM1045217" "GSM1045288"
#> 
#> $sample_in_level$Level_3
#> [1] "GSM1045192" "GSM1045194" "GSM1045221"
#> 
#> $sample_in_level$Level_4
#> [1] "GSM1045194" "GSM1045211" "GSM1045225" "GSM1045243" "GSM1045250"
#> [6] "GSM1045282"
#> 
#> $sample_in_level$Level_5
#>  [1] "GSM1045211" "GSM1045213" "GSM1045225" "GSM1045242" "GSM1045243"
#>  [6] "GSM1045250" "GSM1045282" "GSM1045285" "GSM1045293" "GSM1045301"
#> 
#> $sample_in_level$Level_6
#>  [1] "GSM1045203" "GSM1045206" "GSM1045209" "GSM1045212" "GSM1045213"
#>  [6] "GSM1045214" "GSM1045224" "GSM1045227" "GSM1045237" "GSM1045241"
#> [11] "GSM1045242" "GSM1045248" "GSM1045255" "GSM1045264" "GSM1045266"
#> [16] "GSM1045274" "GSM1045285" "GSM1045293" "GSM1045301"
#> 
#> $sample_in_level$Level_7
#>  [1] "GSM1045200" "GSM1045201" "GSM1045203" "GSM1045206" "GSM1045209"
#>  [6] "GSM1045218" "GSM1045222" "GSM1045227" "GSM1045229" "GSM1045232"
#> [11] "GSM1045233" "GSM1045237" "GSM1045239" "GSM1045240" "GSM1045241"
#> [16] "GSM1045244" "GSM1045252" "GSM1045255" "GSM1045257" "GSM1045259"
#> [21] "GSM1045264" "GSM1045269" "GSM1045270" "GSM1045276" "GSM1045278"
#> [26] "GSM1045294" "GSM1045298" "GSM1045305" "GSM1045306"
#> 
#> $sample_in_level$Level_8
#>  [1] "GSM1045191" "GSM1045195" "GSM1045196" "GSM1045197" "GSM1045198"
#>  [6] "GSM1045199" "GSM1045200" "GSM1045201" "GSM1045204" "GSM1045205"
#> [11] "GSM1045207" "GSM1045210" "GSM1045216" "GSM1045218" "GSM1045219"
#> [16] "GSM1045222" "GSM1045228" "GSM1045231" "GSM1045232" "GSM1045233"
#> [21] "GSM1045238" "GSM1045239" "GSM1045240" "GSM1045245" "GSM1045246"
#> [26] "GSM1045252" "GSM1045254" "GSM1045257" "GSM1045258" "GSM1045259"
#> [31] "GSM1045260" "GSM1045261" "GSM1045263" "GSM1045267" "GSM1045270"
#> [36] "GSM1045271" "GSM1045275" "GSM1045280" "GSM1045283" "GSM1045284"
#> [41] "GSM1045287" "GSM1045296" "GSM1045298" "GSM1045300" "GSM1045303"
#> [46] "GSM1045306" "GSM1045309"
#> 
#> $sample_in_level$Level_9
#>  [1] "GSM1045191" "GSM1045195" "GSM1045196" "GSM1045197" "GSM1045198"
#>  [6] "GSM1045199" "GSM1045202" "GSM1045204" "GSM1045205" "GSM1045208"
#> [11] "GSM1045215" "GSM1045220" "GSM1045228" "GSM1045231" "GSM1045235"
#> [16] "GSM1045236" "GSM1045246" "GSM1045249" "GSM1045253" "GSM1045256"
#> [21] "GSM1045258" "GSM1045260" "GSM1045262" "GSM1045265" "GSM1045267"
#> [26] "GSM1045268" "GSM1045271" "GSM1045273" "GSM1045277" "GSM1045279"
#> [31] "GSM1045280" "GSM1045281" "GSM1045286" "GSM1045289" "GSM1045290"
#> [36] "GSM1045291" "GSM1045292" "GSM1045295" "GSM1045297" "GSM1045299"
#> [41] "GSM1045304" "GSM1045307" "GSM1045309" "GSM1045310"
#> 
#> $sample_in_level$Level_10
#>  [1] "GSM1045202" "GSM1045215" "GSM1045220" "GSM1045223" "GSM1045226"
#>  [6] "GSM1045230" "GSM1045234" "GSM1045235" "GSM1045236" "GSM1045247"
#> [11] "GSM1045249" "GSM1045251" "GSM1045256" "GSM1045262" "GSM1045265"
#> [16] "GSM1045268" "GSM1045272" "GSM1045273" "GSM1045277" "GSM1045279"
#> [21] "GSM1045286" "GSM1045289" "GSM1045291" "GSM1045292" "GSM1045297"
#> [26] "GSM1045304" "GSM1045307" "GSM1045308" "GSM1045310" "GSM1045311"
#> 
#> 
#> $clustering_all_levels
#> $clustering_all_levels$Level_1
#> GSM1045193 GSM1045217 GSM1045302 
#>          1          2          2 
#> 
#> $clustering_all_levels$Level_2
#> GSM1045192 GSM1045217 GSM1045288 
#>          1          1          1 
#> 
#> $clustering_all_levels$Level_3
#> GSM1045192 GSM1045194 GSM1045221 
#>          1          1          1 
#> 
#> $clustering_all_levels$Level_4
#> GSM1045194 GSM1045211 GSM1045225 GSM1045243 GSM1045250 GSM1045282 
#>          1          1          1          1          1          1 
#> 
#> $clustering_all_levels$Level_5
#> GSM1045211 GSM1045213 GSM1045225 GSM1045242 GSM1045243 GSM1045250 GSM1045282 
#>          1          1          1          1          1          1          1 
#> GSM1045285 GSM1045293 GSM1045301 
#>          1          1          1 
#> 
#> $clustering_all_levels$Level_6
#> GSM1045203 GSM1045206 GSM1045209 GSM1045212 GSM1045213 GSM1045214 GSM1045224 
#>          1          1          2          3          4          5          6 
#> GSM1045227 GSM1045237 GSM1045241 GSM1045242 GSM1045248 GSM1045255 GSM1045264 
#>          7          4          2          7          3          2          3 
#> GSM1045266 GSM1045274 GSM1045285 GSM1045293 GSM1045301 
#>          5          8          4          3          9 
#> 
#> $clustering_all_levels$Level_7
#> GSM1045200 GSM1045201 GSM1045203 GSM1045206 GSM1045209 GSM1045218 GSM1045222 
#>          1          1          1          1          1          1          1 
#> GSM1045227 GSM1045229 GSM1045232 GSM1045233 GSM1045237 GSM1045239 GSM1045240 
#>          1          1          1          1          1          1          1 
#> GSM1045241 GSM1045244 GSM1045252 GSM1045255 GSM1045257 GSM1045259 GSM1045264 
#>          1          1          1          1          1          1          1 
#> GSM1045269 GSM1045270 GSM1045276 GSM1045278 GSM1045294 GSM1045298 GSM1045305 
#>          1          1          1          1          1          1          1 
#> GSM1045306 
#>          1 
#> 
#> $clustering_all_levels$Level_8
#> GSM1045191 GSM1045195 GSM1045196 GSM1045197 GSM1045198 GSM1045199 GSM1045200 
#>          1          1          1          1          1          1          1 
#> GSM1045201 GSM1045204 GSM1045205 GSM1045207 GSM1045210 GSM1045216 GSM1045218 
#>          1          1          1          1          1          1          1 
#> GSM1045219 GSM1045222 GSM1045228 GSM1045231 GSM1045232 GSM1045233 GSM1045238 
#>          1          1          1          1          1          1          1 
#> GSM1045239 GSM1045240 GSM1045245 GSM1045246 GSM1045252 GSM1045254 GSM1045257 
#>          1          1          1          1          1          1          1 
#> GSM1045258 GSM1045259 GSM1045260 GSM1045261 GSM1045263 GSM1045267 GSM1045270 
#>          1          1          1          1          1          1          1 
#> GSM1045271 GSM1045275 GSM1045280 GSM1045283 GSM1045284 GSM1045287 GSM1045296 
#>          1          1          1          1          1          1          1 
#> GSM1045298 GSM1045300 GSM1045303 GSM1045306 GSM1045309 
#>          1          1          1          1          1 
#> 
#> $clustering_all_levels$Level_9
#> GSM1045191 GSM1045195 GSM1045196 GSM1045197 GSM1045198 GSM1045199 GSM1045202 
#>          1          1          1          1          1          1          1 
#> GSM1045204 GSM1045205 GSM1045208 GSM1045215 GSM1045220 GSM1045228 GSM1045231 
#>          1          1          1          1          1          1          1 
#> GSM1045235 GSM1045236 GSM1045246 GSM1045249 GSM1045253 GSM1045256 GSM1045258 
#>          1          1          1          1          1          1          1 
#> GSM1045260 GSM1045262 GSM1045265 GSM1045267 GSM1045268 GSM1045271 GSM1045273 
#>          1          1          1          1          1          1          1 
#> GSM1045277 GSM1045279 GSM1045280 GSM1045281 GSM1045286 GSM1045289 GSM1045290 
#>          1          1          1          1          1          1          1 
#> GSM1045291 GSM1045292 GSM1045295 GSM1045297 GSM1045299 GSM1045304 GSM1045307 
#>          1          1          1          1          1          1          1 
#> GSM1045309 GSM1045310 
#>          1          1 
#> 
#> $clustering_all_levels$Level_10
#> GSM1045202 GSM1045215 GSM1045220 GSM1045223 GSM1045226 GSM1045230 GSM1045234 
#>          1          1          1          1          1          1          2 
#> GSM1045235 GSM1045236 GSM1045247 GSM1045249 GSM1045251 GSM1045256 GSM1045262 
#>          1          1          1          1          1          1          1 
#> GSM1045265 GSM1045268 GSM1045272 GSM1045273 GSM1045277 GSM1045279 GSM1045286 
#>          1          1          1          1          1          1          1 
#> GSM1045289 GSM1045291 GSM1045292 GSM1045297 GSM1045304 GSM1045307 GSM1045308 
#>          1          1          1          1          1          1          1 
#> GSM1045310 GSM1045311 
#>          1          1 
#> 
#> 
#> $node_samples
#> $node_samples$Node_1
#> [1] "GSM1045193"
#> 
#> $node_samples$Node_2
#> [1] "GSM1045217" "GSM1045302"
#> 
#> $node_samples$Node_3
#> [1] "GSM1045192" "GSM1045217" "GSM1045288"
#> 
#> $node_samples$Node_4
#> [1] "GSM1045192" "GSM1045194" "GSM1045221"
#> 
#> $node_samples$Node_5
#> [1] "GSM1045194" "GSM1045211" "GSM1045225" "GSM1045243" "GSM1045250"
#> [6] "GSM1045282"
#> 
#> $node_samples$Node_6
#>  [1] "GSM1045211" "GSM1045213" "GSM1045225" "GSM1045242" "GSM1045243"
#>  [6] "GSM1045250" "GSM1045282" "GSM1045285" "GSM1045293" "GSM1045301"
#> 
#> $node_samples$Node_7
#> [1] "GSM1045203" "GSM1045206"
#> 
#> $node_samples$Node_8
#> [1] "GSM1045209" "GSM1045241" "GSM1045255"
#> 
#> $node_samples$Node_9
#> [1] "GSM1045212" "GSM1045248" "GSM1045264" "GSM1045293"
#> 
#> $node_samples$Node_10
#> [1] "GSM1045213" "GSM1045237" "GSM1045285"
#> 
#> $node_samples$Node_11
#> [1] "GSM1045214" "GSM1045266"
#> 
#> $node_samples$Node_12
#> [1] "GSM1045224"
#> 
#> $node_samples$Node_13
#> [1] "GSM1045227" "GSM1045242"
#> 
#> $node_samples$Node_14
#> [1] "GSM1045274"
#> 
#> $node_samples$Node_15
#> [1] "GSM1045301"
#> 
#> $node_samples$Node_16
#>  [1] "GSM1045200" "GSM1045201" "GSM1045203" "GSM1045206" "GSM1045209"
#>  [6] "GSM1045218" "GSM1045222" "GSM1045227" "GSM1045229" "GSM1045232"
#> [11] "GSM1045233" "GSM1045237" "GSM1045239" "GSM1045240" "GSM1045241"
#> [16] "GSM1045244" "GSM1045252" "GSM1045255" "GSM1045257" "GSM1045259"
#> [21] "GSM1045264" "GSM1045269" "GSM1045270" "GSM1045276" "GSM1045278"
#> [26] "GSM1045294" "GSM1045298" "GSM1045305" "GSM1045306"
#> 
#> $node_samples$Node_17
#>  [1] "GSM1045191" "GSM1045195" "GSM1045196" "GSM1045197" "GSM1045198"
#>  [6] "GSM1045199" "GSM1045200" "GSM1045201" "GSM1045204" "GSM1045205"
#> [11] "GSM1045207" "GSM1045210" "GSM1045216" "GSM1045218" "GSM1045219"
#> [16] "GSM1045222" "GSM1045228" "GSM1045231" "GSM1045232" "GSM1045233"
#> [21] "GSM1045238" "GSM1045239" "GSM1045240" "GSM1045245" "GSM1045246"
#> [26] "GSM1045252" "GSM1045254" "GSM1045257" "GSM1045258" "GSM1045259"
#> [31] "GSM1045260" "GSM1045261" "GSM1045263" "GSM1045267" "GSM1045270"
#> [36] "GSM1045271" "GSM1045275" "GSM1045280" "GSM1045283" "GSM1045284"
#> [41] "GSM1045287" "GSM1045296" "GSM1045298" "GSM1045300" "GSM1045303"
#> [46] "GSM1045306" "GSM1045309"
#> 
#> $node_samples$Node_18
#>  [1] "GSM1045191" "GSM1045195" "GSM1045196" "GSM1045197" "GSM1045198"
#>  [6] "GSM1045199" "GSM1045202" "GSM1045204" "GSM1045205" "GSM1045208"
#> [11] "GSM1045215" "GSM1045220" "GSM1045228" "GSM1045231" "GSM1045235"
#> [16] "GSM1045236" "GSM1045246" "GSM1045249" "GSM1045253" "GSM1045256"
#> [21] "GSM1045258" "GSM1045260" "GSM1045262" "GSM1045265" "GSM1045267"
#> [26] "GSM1045268" "GSM1045271" "GSM1045273" "GSM1045277" "GSM1045279"
#> [31] "GSM1045280" "GSM1045281" "GSM1045286" "GSM1045289" "GSM1045290"
#> [36] "GSM1045291" "GSM1045292" "GSM1045295" "GSM1045297" "GSM1045299"
#> [41] "GSM1045304" "GSM1045307" "GSM1045309" "GSM1045310"
#> 
#> $node_samples$Node_19
#>  [1] "GSM1045202" "GSM1045215" "GSM1045220" "GSM1045223" "GSM1045226"
#>  [6] "GSM1045230" "GSM1045235" "GSM1045236" "GSM1045247" "GSM1045249"
#> [11] "GSM1045251" "GSM1045256" "GSM1045262" "GSM1045265" "GSM1045268"
#> [16] "GSM1045272" "GSM1045273" "GSM1045277" "GSM1045279" "GSM1045286"
#> [21] "GSM1045289" "GSM1045291" "GSM1045292" "GSM1045297" "GSM1045304"