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CIComputeR

Introduction

CIcomputeR WEB is a Shiny application which aims to compute two-combination drug synergy using the Chou-Talalay Combination Index (CI). The theoretical basis behind CI computation can be found across various literature, such as [1,2]. In brief, the value of CI can explain whether the combination of two drug treatments shows synergistic, additive, or antagonistic effects by fitting a linear model with respect to treatment group population. The program can be accessed here: https://brianjmpark.shinyapps.io/cicomputer/

Run-through

Single Analysis

The application takes a tabular data containing the two drug concentrations and cell response measurements (typically obtained from a cell viability assay, such as the MTT) as input. The column headers for these required fields must be provided to the program in the appropriate fields.

  • Conc. A = concentration for the one of the drugs.
  • Conc. B = concentration for the other drug.
  • Response = viability or inhibition values in decimals (i.e., <= 1) or in percentages (i.e., <= 100).

It is important to note that for Single Analysis, the data should correspond to one unique drug-drug pair. This means that for each unique combination of two drug doses, there should only be one unique cell readout value. For datasets containing multiple drug pairs, the Batch Analysis tab must be used instead.

After file input, the user must select whether the values under the column Response corresponds to viability or inhibition values and checks the box which indicates whether these values are in decimals or percentages.

Executing the program generates a table containing the effect size and the calculated CI.

Batch Analysis

This analysis tab performs the same analysis as Single Analysis, except it accepts multiple drug-drug pairs at once given that a column specifying a unique identifier for each pair is provided in the appropriate field:

  • ID = unique identifier for a drug-drug pair (i.e., if data contains n = 3 drug-pairs, this column should contain 3 unique identifiers)

Running this analysis outputs a table where each unique identifier is assigned a column containing CI values.

R dependencies

  • shiny
  • shinythemes
  • dplyr & tidyr
  • DT
  • htmltools
  • shinycssloaders

R sessionInfo()

R version 4.0.5 (2021-03-31)
Platform: x86_64-apple-darwin17.0 (64-bit)
Running under: macOS Big Sur 11.2.3

Matrix products: default
LAPACK: /Library/Frameworks/R.framework/Versions/4.0/Resources/lib/libRlapack.dylib

locale:
[1] en_CA.UTF-8/en_CA.UTF-8/en_CA.UTF-8/C/en_CA.UTF-8/en_CA.UTF-8

attached base packages:
[1] stats     graphics  grDevices utils     datasets  methods   base     

other attached packages:
 [1] rsconnect_0.8.25  forcats_0.5.1     stringr_1.4.0     dplyr_1.0.5       purrr_0.3.4       readr_1.4.0       tidyr_1.1.3       tibble_3.1.1     
 [9] ggplot2_3.3.3     tidyverse_1.3.1   DT_0.26           shinythemes_1.2.0 shiny_1.6.0      

loaded via a namespace (and not attached):
 [1] httr_1.4.2          sass_0.4.2          jsonlite_1.7.2      splines_4.0.5       modelr_0.1.8        bslib_0.4.0         assertthat_0.2.1   
 [8] askpass_1.1         BiocManager_1.30.12 cellranger_1.1.0    yaml_2.2.1          pillar_1.6.0        backports_1.2.1     lattice_0.20-41    
[15] glue_1.4.2          digest_0.6.27       promises_1.2.0.1    rvest_1.0.3         colorspace_2.0-0    htmltools_0.5.3     httpuv_1.6.0       
[22] Matrix_1.3-2        pkgconfig_2.0.3     broom_0.7.12        haven_2.4.1         xtable_1.8-4        scales_1.1.1        later_1.2.0        
[29] openssl_1.4.3       mgcv_1.8-34         generics_0.1.0      farver_2.1.0        ellipsis_0.3.1      cachem_1.0.4        withr_2.4.2        
[36] sourcetools_0.1.7   cli_3.1.0           magrittr_2.0.1      crayon_1.4.1        readxl_1.3.1        mime_0.10           memoise_2.0.0      
[43] fs_1.5.0            fansi_0.4.2         nlme_3.1-152        xml2_1.3.3          tools_4.0.5         hms_1.0.0           lifecycle_1.0.0    
[50] munsell_0.5.0       reprex_2.0.0        packrat_0.7.0       compiler_4.0.5      jquerylib_0.1.4     rlang_1.0.6         grid_4.0.5         
[57] rstudioapi_0.13     htmlwidgets_1.5.4   crosstalk_1.1.1     labeling_0.4.2      gtable_0.3.0        curl_4.3            DBI_1.1.1          
[64] R6_2.5.0            lubridate_1.7.10    fastmap_1.1.0       utf8_1.2.1          stringi_1.5.3       Rcpp_1.0.6          vctrs_0.3.7        
[71] dbplyr_2.1.1        tidyselect_1.1.0   

App hosting

This app is hosted on the shinyapps.io server and deployed using the R package rsconnect.

Citations

  1. Ashton, John C. "Drug combination studies and their synergy quantification using the Chou–Talalay method." Cancer research 75.11 (2015): 2400-2400.
  2. Zhang, Ning, Jia-Ning Fu, and Ting-Chao Chou. "Synergistic combination of microtubule targeting anticancer fludelone with cytoprotective panaxytriol derived from panax ginseng against MX-1 cells in vitro: experimental design and data analysis using the combination index method." American journal of cancer research 6.1 (2016): 97.

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Shiny application for calculating the Chou-Talalay Combination Index (CI) for drug synergy computation

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