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molnet (version 0.1.0)

Predicting Differential Drug Response using Multi-Omics Networks

Description

Networks provide a means to incorporate molecular interactions into reasoning, but on the omics-level, they are currently mainly used to combine genomic and proteomic information. We here present a novel network analysis pipeline that enables integrative analysis of multi-omics data including metabolomics. It allows for comparative conclusions between two different conditions, such as tumor subgroups, healthy vs. disease, or generally control vs. perturbed. Our approach focuses on interactions and their strength instead of on node properties and includes molecules with low abundance and unknown function. We use correlation-induced networks that are reduced and combined to form heterogeneous, multi-omics molecular networks. Prior information such as metabolite-protein interactions are incorporated. A semi-local, path-based integration step denoises the network and ensures integrative conclusions. As case studies, we investigate differential drug response in breast cancer tumor datasets providing proteomics, transcriptomics, phospho-proteomics and metabolomics data and contrasting patients with different estrogen receptor status. Our proposed pipeline leverages multi-omics data for differential predictions, e.g. on drug response, and includes prior information on interactions. The case study presented in the vignette uses data published by Krug (2020) . The package license applies only to the software and explicitly not to the included data.

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Version

Install

install.packages('molnet')

Monthly Downloads

81

Version

0.1.0

License

MIT + file LICENSE

Maintainer

Katharina Baum

Last Published

August 6th, 2021

Functions in molnet (0.1.0)

calculate_interaction_score

Calls a python script to calculate interaction score for combined graphs
molnet_settings

Create global settings variable for molnet pipeline
drug_target_interaction_example

Drug target interaction example data
generate_individual_graphs

Builds graphs from specified network layers
generate_reduced_graph

Generate a reduced iGraph
check_connection

Checks connection
drug_targets_example

Drug target nodes in combined network
check_drug_target

Check drug target interaction data
mrna_data

mRNA expression data
check_drug_targets_in_layers

Check drug target and layer data
return_errors

Return detected errors
sample_size

Sample size for correlation computation
check_input

Check pipeline input data for required format
check_layer

Check layer input
graph_metrics

Analyses metrics of an iGraph object
get_layer_setting

Get layer settings
interaction_score_graphs_vignette

Interaction score graphs for vignette
differential_score

The absolute difference of interaction score of two groups
differential_score_graph_example

Differential graph
layers_example

Formatted layers object
%>%

Pipe operator
set_cluster

Create and register cluster
scaleFreeFitIndex_alternative

Alternative implementation of WGCNA::scaleFreeFitIndex
combined_graphs_example

Combined graphs
protein_data

Protein data
drug_gene_interactions

Drug-gene interactions
drug_response_score_example

Drug response score
individual_graphs_example

Individual graphs
corPvalueStudentParallel

Compute p-values for upper triangle of correlation matrix in parallel
load_interaction_score_output

Loads output of python script for interaction score calculation
install_python_dependencies

Installs python dependencies needed for interaction score computation
make_connection

Specify connection between two individual layers
shutdown_cluster

Shutdown cluster and remove corresponding connections
phosphoprotein_data

Phosphosite data
pickHardThreshold_alternative

Alternative implementation of WGCNA::pickHardThreshold
start_pipeline

Execute all molnet-pipeline steps sequentially
inter_layer_edgelist_by_id

Interlayer conntections by identifiers
check_sensible_connections

Check connection and layer data
inter_layer_edgelist_by_table

Interaction table to iGraph graph object
combine_graphs

Combining graphs by adding inter-layer edges
find_targets

Filter drug target nodes
chunk_2gether

Create chunks from two vectors for parallel computing
generate_combined_graphs

Combines individual layers to a single graph
make_drug_target

Reformat drug-target-interaction data
make_layer

Creates individual molecular layers from raw data and unique identifiers
create_unique_layer_node_ids

Assigns node IDs to the biological identifiers across a graph layer
get_drug_response_score

Calculate drug response score
chunk

Create chunks from a vector for parallel computing
get_layer

[INTERNAL] Fetch layer by name from layer object
determine_drug_targets

Determine drug target nodes in network
network_reduction_by_pickHardThreshold

Reduces network based on WGCNA::pickHardThreshold function
target_edge_list

Edges adjacent to target nodes
write_interaction_score_input

Write edge lists and combined graphs to files
network_reduction_by_p_value

Reduce the the entries in an adjacency matrix by thresholding on p-values
interaction_score_graphs_example

Interaction score graphs
metabolite_protein_interaction

Metabolite protein interaction data
interaction_score

Computes interaction score for combined graphs
metabolite_data

Metabolomics data