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PANACEA: Personalized Network-based Anti-Cancer Therapy Evaluation

Identification of the most appropriate pharmacotherapy for each patient based on genomic alterations is a major challenge in personalized oncology. PANACEA is a collection of personalized anti-cancer drug prioritization approaches utilizing network methods. The methods utilize personalized “driverness” scores from driveR to rank drugs, mapping these onto a protein-protein interaction network. The “distance-based” method scores each drug based on these scores and distances between drugs and genes to rank given drugs. The “RWR” method propagates these scores via a random-walk with restart framework to rank the drugs.

The method is described in detail in Ulgen E, Ozisik O, Sezerman OU. PANACEA: network-based methods for pharmacotherapy prioritization in personalized oncology. Bioinformatics. 2023 Jan 1;39(1):btad022. https://doi.org/10.1093/bioinformatics/btad022

Installation

You can install the latest release version of PANACEA from CRAN via:

install.packages("PANACEA")

You can install the development version of PANACEA from GitHub with:

# install.packages("devtools") @ if you don't have devtools installed
devtools::install_github("egeulgen/PANACEA", build_vignettes = TRUE)

Usage

The wrapper function score_drugs() can be used to score and rank drugs for an individual tumor sample via the “distance-based” or “RWR” method. The required inputs are:

  • driveR_res: data frame of driveR results. Details on how to obtain driveR output are provided in this vignette
  • drug_interactions_df: data frame of drug-gene interactions (defaults to interactions from DGIdb expert-curated sources)
  • W_mat: (symmetric) adjacency matrix for the protein interaction network (defaults to STRING v11.5 interactions with combined score > .4)
  • method: scoring method (one of “distance-based” or “RWR”)

Example Usage

For detailed information on how to use PANACEA, please see the vignette “How to use PANACEA” via vignette("how_to_use") or visit this link

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Version

Install

install.packages('PANACEA')

Monthly Downloads

506

Version

1.0.1

License

MIT + file LICENSE

Issues

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Maintainer

Ege Ulgen

Last Published

August 19th, 2023

Functions in PANACEA (1.0.1)

toy_W_mat

Toy Adjacency Matrix (for examples)
score_drugs_distance_based

Distance-based Scoring of Drugs
example_scores_dist

Example PANACEA "distance-based" Method Result
convert2alias

Convert Input Gene Symbols to Alias
PANACEA

PANACEA: Personalized Network-based Anti-Cancer Therapy Evaluation
example_driveR_res

Example driveR Result
Laplacian.norm

Graph Laplacian Normalization
STRING_adj_df

Adjacency List for STRING v11.5 - High Confidence Interactions
adj_list2mat

Turn Adjacency List into Adjacency Matrix
score_drugs

Scoring of Drugs via Network-based Methods
network_propagation

Network Propagation (Random-walk with Restart)
score_drugs_RWR_based

RWR-based Scoring of Drugs
process_drug_target_interactions

Process Drug-Target Interactions
add_drugs_as_nodes

Add Drugs as Nodes
DGIdb_interactions_df

DGIdb Interactions Expert-curated Sources
example_scores_RWR

Example PANACEA "RWR" Method Result