MORGOTH

This is the implementation of our novel random forest (RF)-based approach for Multivariate classificatiOn and Regression increasinG trustwOrTHiness (MORGOTH). A detailed description and application of the model can be found in our pre-print `Increasing trustworthiness of machine learning-based drug sensitivity prediction with a multivariate random forest approach'. MORGOTH can be used to simultaneously perform classification and regression using a novel objective function during the training, which is a linear combination of classification and regression error. Moreover, it offers the possibility to perform conformal prediction (CP), which can be used to obtain reliable classification and regression results. A more detailed explanation of CP and the framework we use can be found in our article 'Reliable anti-cancer drug sensitivity prediction and prioritization'. Additionally, MORGOTH provides a graph representation of the random forest to address model interpretability, and a cluster analysis of the leaves to measure the dissimilarity of new inputs from the training data to account for its reliability and robustness. The scripts and processed data needed to reproduce the results presented in our manuscript can be found on Zenodo.

For issues and questions, please contact Lisa-Marie Rolli (lisa-marie.rolli[at]uni-saarland.de) or Kerstin Lenhof (research[at]klenhof.de).

Installation

You can install our morgoth package using pip:

pip install morgoth

used python3 libraries: fireducks pandas numpy typing math bisect operator copy sklearn time scipy collections multiprocessing functools re

Usage

Command line usage

An exemplary use is running our provided main as a module, which you can call after downloading the Example_Data folder from our GitHub.

python3 -m morgoth Example_Data/example_Json_config.json

Note that the directory tree should be kept and the path to the output folder should be edited in the file Example_Data/example_JSON_config.json. The prediction results for classification will be found in <output_dir><analysis_name>_ClassificationResultsFile1.txt and the regression results are stored in <output_dir><analysis_name>_<1-error_rate>_RegressionResultsFile1.txt. If if the field swap_test_calibration in the config file is set to 'True' there will be one additional file per task, respectively, where the '1' in the file name is replaced by a '2'. If a distance measure is given in the config, <output_dir><analysis_name>_SilhouetteScoresTrainSamples_<distance>.txt and <output_dir><analysis_name>_SilhouetteScoresTestSamples_<distance>.txt will contain the silhouette scores for the training and test samples, respectively. If draw_graph is set to True, the files <output_dir>/<analysis_name>_<sample_name>.dot contain the sample specific graphs and <output_dir><analysis_name>__graph_whole_forest.dot and <output_dir><analysis_name>__graph_average_whole_forest.dot contain the graph for the whole test set with either the raw count across all samples as edge weight or averaged by the number of test samples, respectively.

Example Python code

import pandas as pd
from morgoth import MORGOTH
import numpy as np
from sklearn.metrics import r2_score, matthews_corrcoef

seed = 42
# change to your input data directory
input_dir = 'Example_Data/'
# change to your output data directory
output_dir = 'Example_Data/output/'
# full feature matrix
X = pd.read_csv(f'{input_dir}/expression_matrix.txt', index_col=0, sep='\t')
# regression data is split in train and test
y_reg_train = pd.read_csv(
    f'{input_dir}/Training_Irinotecan_scores.txt', index_col=0, sep='\t')
y_reg_test = pd.read_csv(
    f'{input_dir}/Test_Irinotecan_scores.txt', index_col=0, sep='\t')
# binary contains all samples
y_binary_full = pd.read_csv(
    f'{input_dir}/Irinotecan_Discretized.txt', index_col=0, sep='\t')
# thus we split it into train and test
y_binary_train = y_binary_full.loc[y_reg_train.index, :]
y_binary_test = y_binary_full.loc[y_reg_test.index, :]

# for multioutput we need an array of arrays of size 2
y_train = np.array([np.array(
    [y_reg_train.values[i], y_binary_train.values[i]]) for i in range(len(y_reg_train))])
y_test = np.array([np.array([y_reg_test.values[i], y_binary_test.values[i]])
                  for i in range(len(y_reg_test))])

# create output_files
time_file = f'{output_dir}/ElapsedTimeFitting.txt'
sample_info_file = f'{output_dir}/Additional_Sample_Information.txt'
leaf_assignment_file_train = f'{output_dir}/Training_Set_LeafAssignment.txt'
feature_imp_output_file = f'{output_dir}/Feature_Importance.txt'
silhouette_score_file = f'{output_dir}/Silhouette_Score.txt'
silhouette_score_train_file = f'{output_dir}Silhouette_Score_Train.txt'
cluster_assignment_file = f'{output_dir}/Cluster_Assignment.txt'

# subset source to the 100 genes with the highest score
gene_scores = pd.read_csv(
    f'{input_dir}/gene_score_list.txt', sep='\t', names=['gene', 'score'])

# find top 100 genes
gene_scores.sort_values(by='score', ascending=False, inplace=True)
gene_scores.set_index('gene', inplace=True, drop=True)
top_100 = gene_scores.index.values[:100]

# subset the feature matrix
X_train_subset = X.loc[y_reg_train.index, top_100]
X_test_subset = X.loc[y_reg_test.index, top_100]

# construct morgoth object
mult_rf = MORGOTH(X_train=X_train_subset, y_train=y_train, sample_names_train=X_train_subset.index,
                  criterion_class='gini', criterion_reg='mse', min_number_of_samples_per_leaf=10, number_of_trees_in_forest=500, analysis_name='example_usage',
                  number_of_features_per_split='sqrt', class_names=[0, 1], output_format='multioutput', threshold=[0.499358], time_file=time_file,
                  sample_weights_included='simple', random_state=seed, max_depth=20, impact_classification=0,
                  sample_info_file=sample_info_file, leaf_assignment_file_train=leaf_assignment_file_train, feature_imp_output_file=feature_imp_output_file,
                  tree_weights=True, silhouette_score_file=silhouette_score_file, distance_measure='', cluster_assignment_file=cluster_assignment_file,
                  draw_graph=False, graph_path=output_dir,
                  silhouette_score_train_file=silhouette_score_train_file)
# fit and predict
mult_rf.fit()
y_pred = mult_rf.predict(X_test=X_test_subset)
# split output in regression and classification data (in case you use multioutput)
split = np.hsplit(y_pred, 2)
y_pred_reg = split[0].flatten()
y_pred_class = split[1].flatten()

print(f'MCC: {matthews_corrcoef(y_pred=y_pred_class, y_true=y_binary_test.values)}')
print(f'R2: {r2_score(y_pred=y_pred_reg, y_true=y_reg_test.values)}')