Review Article

Biomolecular Network-Based Synergistic Drug Combination Discovery

Table 1

Tools used to analyze drug combination data.

Tool nameTool typeReference model(s)Input dataBrief description

CompuSyn [25]Free softwareLoewe additivity modelDose-response dataCompuSyn only allows for manual input of one drug combination at a time
Synergyfinder [26]R packageHSA, Loewe additivity, Bliss independenceDose-response dataSynergyfinder is implementations for all the popular synergy scoring models for drug combinations, including HAS, Loewe, Bliss, and ZIP [10]
Mixlow [27]R packageA nonlinear mixed-effects modelDose-response dataMixlow used a nonlinear mixed-effects model to estimate parameters of dose-response curves and required experimental design where the ratio of two drugs in a combination is fixed
COMBIA [28]R packageBliss independence, Loewe additivityData from wet-lab experimentalData from wet-lab experimental platforms can be directly used
MacSynergyII [29]Free softwareBliss independenceDose-response dataMacSynergy II is essentially an Excel file and it scales the input data to %inhibition using positive and negative controls
Combenefit [30]Free softwareHSA, Loewe additivity, Bliss independenceDose-response dataCombenefit has advanced graphical capabilities and can be applied to model-based quantification of drug combinations in single and high-throughput settings
Combinatorial Drug Assembler [31] (http://cda.i-pharm.org/)Free web app implementationNoneDisease-related signaling pathway componentsCDA performs expression pattern matching between input gene sets and 6,100 molecule-treated expression profiles of the connectivity map to list up best pattern matching single drugs/combinatorial drug pairs
Synergy Maps [32]
(http://richlewis42.github.io/synergy-maps/)
Free web app implementationNoneDrugs or drug combinations in two datasets [25, 26]Synergy Maps can simultaneously represent individual compound properties and their interactions
DT-Web [33]
(http://alpha.dmi.unict.it/dtweb/)
Free web app implementationNoneThe name or the accession number of a drug/targetA web-based application for drug-target interaction and drug combination prediction
TIMMA-R [34]R packageLogic-based networkDrugs’ polypharmacological profiles and drug sensitivity profiles from a given cancer cell lineTIMMA-R predicts the effects of drug combinations based on their binary drug target interactions and single-drug sensitivity profiles