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 (“cor”), 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 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 <- 5
percent_overlap <- 40
distance_type <- "cor"
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 "silhouette"
                                 # (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: DGSA.

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.

DGSA_object <- DGSA(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 DGSA is started
#> 
#> BLOCK I: The pre-process DGSA is finished

Second step of the process: Select the genes within the DGSA 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 to summarise each vector of each individual in a single data. This function takes into account the survival associated with each gene.

geneSelection_object <- geneSelection(DGSA_object, gen_select_type, percent_gen_select)
#> [1] "DGSA_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 DGSA (RBR, duda).

# 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
geneSelection_object <- geneSelection(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)
#> 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 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 DGSA and gene selection

mapper_object <- mapper(full_data = geneSelection_object[["genes_disease_component"]], 
                        filter_values = geneSelection_object[["filter_values"]],
                        num_intervals = num_intervals,
                        percent_overlap = percent_overlap, distance_type = distance_type,
                        clustering_type = clustering_type,
                        linkage_type = linkage_type, 
                        optimal_clustering_mode = optimal_clustering_mode)
#> 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)