KDDANet

A computational framework for uncovering hidden genes mediating Known Drug-Disease Associations (KDDAs)

Version

1.0.0

Author

Hua Yu and Lu Lu

Description

This software enables genome-wide discovery of hidden genes and modules mediating KDDAs through implementing minimum cost flow optimization, combined with depth-first searching and graph clustering on a unified flow network model

Installation

KDDANet can be installed as follow:

• I) Add KDDANet to PATH variable

git clone https://github.com/huayu1111/KDDANet.git
export PATH=path_to_KDDANet:$PATH
cd path_to_KDDANet
chmod +x lpsolver

• II) Download MCL software (Version 'mcl-14-137') from https://micans.org/mcl/ and install:

tar xzf mcl-14-137.tar.gz
cd mcl-14-137
./configure --prefix=$HOME/local
make install
export PATH=$HOME/local/bin:$PATH

Running

• I) Step 1: Obtaining the solution of minimum cost flow optimization problem for each query drug (disease) and all its related diseases (drugs)

perl getSolution.pl -dr <DRUG_FILE> -di <DISEASE_FILE> -n <NET_FILE> -dt <DRUG_TARGET_FILE> -dg <DISEASE_GENE_FILE> --dd <DRUG_DISEASE_ASSOCIATION_FILE> -o <OUTPUT_DIR> -gmin <GAMMA_MIN> -gmax <GAMMA_MAX> -gstep GAMA_INCREMENT -opt <CONTEXT> -h
-dr  <DRUG_FILE>, A single column text file (default DrugBank drugs)
-di  <DISEASE_FILE>, A single column text file (default OMIM diseases)
-n  <NET_FILE>, A tab-delimited text file (default HumanNet)
-dt <DRUG_TARGET_FILE> A tab-delimited text file (default DrugBank gene targets)
-dg <DISEASE_GENE_FILE> A tab-delimited text file (default disease-related genes extracted from literature [1])
-dd <DRUG_DISEASE_ASSOCIATION_FILE> A tab-delimited text file (default drug-disease association contained in CTD database)
-o  OUTPUT_DIR for output files (default './result/')
-gmin  GAMMA_MIN	(default 4)
-gmax  GAMMA_MAX	(default 12)
-gstep  GAMMA_INCREMENT (default 1)
-opt <CONTEXT> (SDrTDi or SDiTDr, default SDrDTi)
-h  help

Input files format:

1. <DRUG_FILE> / <DISEASE_FILE>
   A single column text file provides drug or disease information
   Format: DRUG_ID/DISEASE_ID

2. <NET_FILE>
   A tab-delimited text file provides interactome network information
   Format: G1_ID G2_ID Weight

3. <DRUG_TARGET_INFO> / <DISEASE_GENE_INFO>
   A tab delimited text file provides drug's target information / disease-related gene information
   Format: DRUG_ID TARGET_GENE_ID / DISEASE_ID RELATED_GENE_ID

4. <DRUG_DISEASE_ASSOCIATION_FILE>
   A tab delimited text file provides drug-disease association information
   Format: DRUG_ID DISEASE_ID

An example for running this step:

perl getSolution.pl -dr ../inputdata/DrugBank.Drug.Info.txt -di ../inputdata/OMIM.Disease.Info.txt -n ../inputdata/HumanNet.txt -dt ../inputdata/Used_Drug_Target_Data.txt -dg ../inputdata/Used_Disease_Gene_Data.txt --dd ../inputdata/KDDAs_Total.txt -o ../result/ -gmin 4 -gmax 4 -gstep 1 -opt SDrTDi

This command will obtain the solution for each query drug/disease and its related diseases/drugs in the directory of ../result/$gamma for each gamma value

• II) Step2: Extracting the subnetwork of genes mediating individual KDDA from the solution using depth-first searching
  

perl getNodeFlowAndEdgeFlow.pl --indir <IN_DIR> --outdir <OUT_DIR>
--indir <IN_DIR> the directory used to place result files of solutions
--outdir <OUT_DIR> the directory used to place node flow file and edge flow file

 perl getGeneInteractionSubNetForEachKDDAUsingDFS.pl --infile <IN_FILE> --outDir <OUT_DIR>
--infile <IN_FILE> the edge flow file
--outDir <OUT_DIR> the directory used to place gene interaction subnetwork for each known drug-disease association

An example for running this step:

perl getNodeFlowAndEdgeFlowFromSolutions.pl --indir ../results/4 --outdir  ../results/4
perl getGeneInteractionSubNetForEachKDDAUsingDFS.pl.pl --infile ../results/4/opti_edge_flow.txt --outDir  ../results/4/subnetworks

• III) Step3: Identifying gene modules from the subnetwork using MCL algorithm

perl ObtainModuleInfoByMCL.pl --indir <IN_DIR> --outdir <OUT_DIR>
--indir <IN_DIR> the directory used to place result files of gene subnetworks
--outdir <OUT_DIR> the directory used to place gene module files

An example for running this step:

perl ObtainModuleInfoByMCL.pl --indir ../results/4/subnetworks --outDir  ../results/4/modules

Input data

The directory of ./inputdata/ provides the datasets used in our paper

License

KDDANet is licensed under the GPL version 3 or any later version

For any questions, please contact:

Hua Yu (yuhua200886@163.com) or Lu Lu (tkrwy@126.com)