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DDCV Information

A Visualized Shiny App to Evaluate Drug-Drug Interaction

Project status: Version 4.0

<Author: Tongwu Zhang>

Website: http://xtmgah.shinyapps.io/DDCV/

License: DDCV is freely available under a GNU Public License (Version 2)

Citation: Please cite the following article if you use DDCV in your research

<Tongwu Zhang et al. Drug-Drug Combination Visualization (DDCV): Evaluation of Drug-Drug Interactions using Shiny by RStudio. 2015.(In Prepare)> Tongwu Zhang et al. Drug-Drug Combination Visualization (DDCV): Evaluation of Drug-Drug Interactions using Shiny by RStudio. 2015.

Description

Evaluation of synergy or antagonism of agents used in combination therapy is an integral part of cancer chemotherapy development. Simultaneous use of multiple methods enhances the donfidence of combination therapy. We developed a visualized R Shiny App to evaluated drug-drug synergy, additivity and antagonism using several published methodologies, including isobologram, combination index, curve-shift and universal surface response analysis.

Dependencies

• R

• R package: ggplot2, shiny, reshape2, gplots, plyr, lattice, scatterplot3d, d3heatmap

Downloading

Both through "git clone" or directly download comparessed file are avaiable:

git clone "https://github.com/xtmgah/DDCV.git"
cd DDCV

Running

There are two methods runing with or without downloading software.

GitHub repository:

library(shiny)
options(download.file.method="wget",download.file.extra=" --no-check-certificate")
shiny::runGitHub('DDCV','xtmgah')

or

library(shiny)
options(download.file.method="wget",download.file.extra=" --no-check-certificate")
runUrl('https://github.com/xtmgah/DDCV/archive/master.zip')

Local running

cd DDCV

then

library(shiny)
runApp("../DDCV")

or

library(shiny)
source("DDCV.R")

Input CSV foramt

Matrix file format:

DrugA/DrugB	5000	5000	4000	4000	3000	3000	2250	2250	1500	1500	1000	1000	500	500	0	0
0.25	1609	1073	1459	1597	4112	3195	3709	3929	4661	5253	5539	5805	10590	10184	10931	15020
0.25	1624	1898	2248	2937	3943	5139	3709	4340	4914	5614	6187	11652	9942	20365	9838	16601
0.20	2493	1498	2688	2091	5485	5324	4496	4492	5523	5174	8353	9833	19715	19214	12129	27393
0.20	2355	1950	2935	3383	5765	7162	4391	4391	4418	5265	8693	15340	15973	30613	11614	23119
0.16	3260	1390	2459	1755	5411	5889	3652	4210	4529	5162	8222	9413	18849	18455	16028	29547
0.16	3062	1921	2525	2055	6834	6323	3916	4283	4752	4956	10748	8628	15369	16258	15027	26021
0.13	3151	2039	2791	2601	6610	7918	4368	5078	5688	6760	12354	11062	18436	17563	15035	30379
0.13	3135	1575	3027	1653	5787	6293	4482	4529	4712	5195	11267	10588	16639	16787	15949	27543
0.10	3050	1965	2269	2729	6574	8452	4877	5601	6234	6105	14047	12401	20608	21756	23021	33000
0.10	3436	2140	3240	1989	5352	6795	4087	5096	5873	6760	13580	12332	18349	21378	23320	30949
0.07	4124	2640	3865	2718	8161	7999	5596	6374	6277	7373	17441	14634	25133	27359	30202	39171
0.07	3554	2293	3212	3261	7027	9090	5595	6192	6669	7505	18393	12325	22932	24509	27126	33748
0.05	5348	2820	6340	3404	10168	11130	7206	8805	8285	8729	18293	16843	28392	31007	34998	42773
0.05	4735	2577	5241	2038	10784	9490	5159	9057	8954	9138	18213	15769	27259	27927	35539	40335
0.00	11291	13751	17858	13083	35769	36605	36398	37620	35052	36365	33880	33576	42494	41642	46640	46467
0.00	7244	13013	12074	9639	32487	31180	32986	34580	32642	35208	32367	32937	39519	41412	45332	46843

.........

Column3 file format:

DrugA	DrugB	Intensity
5000.00	73.4	921
5000.00	73.4	1011
2500.00	73.4	995
2500.00	73.4	1020
1250.00	73.4	976
1250.00	73.4	982
625.00	73.4	994
625.00	73.4	993
312.50	73.4	1018
312.50	73.4	1087
156.25	73.4	967
156.25	73.4	1003
78.12	73.4	997
78.12	73.4	1026
39.06	73.4	1031
39.06	73.4	982
19.53	73.4	1036
19.53	73.4	1046
9.77	73.4	997
9.77	73.4	995
0.00	73.4	1013
0.00	73.4	995
0.00	73.4	1018
0.00	73.4	981
5000.00	73.4	1059
5000.00	73.4	982
2500.00	73.4	1038
2500.00	73.4	995
1250.00	73.4	961
1250.00	73.4	1041
625.00	73.4	997
625.00	73.4	1040
312.50	73.4	1031
312.50	73.4	986
156.25	73.4	1000
156.25	73.4	1030
78.12	73.4	1035
78.12	73.4	1002
39.06	73.4	968
39.06	73.4	1006
19.53	73.4	957
19.53	73.4	1009
9.77	73.4	1048
9.77	73.4	1014
0.00	73.4	936
0.00	73.4	971
0.00	73.4	973
0.00	73.4	1024
5000.00	8.4	1093
5000.00	8.4	1040

..............

Example

Parameter Panel

IC50 Prediction

Single and Combination Drug IC50:

  | DrugA | DrugB | Combination (IC50 equivalent dose)  |

------| ------ | ------ |------ | IC50 | 2.01 | 6.24 | 0.64 |

Response Matrix Profile

Median Effect

Isobologram

Isobologram analysis has been used to make a graphical presentation of the interaction of two drugs.

Combination Index

Combination index provides a quantitative measure of the extent of drug interaction at a given effect level.

Curve-shift

Curve-shift analysis allows simultaneous presentation of the studied concentration-effect curves of single-agent and combination treatments in a single plot.

Universal Surface Response

Universal surface model approach provides a single value summarizing the nature of interaction for the totality of data on the combinations.

Contour Plots of Raw Data