In sigven/oncoEnrichR: Cancer-dedicated gene set interpretation

Synthetic lethality

Using recently published predictions on synthetic lethal interactions in human cancer cell lines (De Kegel et al., Cell Syst., 2021), we here show whether members of the query set are found among these interactions.
Note that predictions in the study by De Kegel et al. are provided for human gene paralogs only
In the tables below, predictions below the 50% percentile are ignored (the complete set can be found in the Excel output of oncoEnrichR). Additional properties of each predicted pair of interactors are included for filtering, including:
Prediction score and percentile
Percent sequence identity between the genes
Size of gene paralog family
The higher the prediction score, the more confident the prediction is with respect to a synthetic lethality interaction. Interactions are here ranked according to confidence (percentile), visualized in varying shades of blue (from low-confident interactions to high-confident interactions ).

sl_interactions <- list()
sl_interactions[['a_b']] <- data.frame()
sl_interactions[['a_only']] <- data.frame()
active_tab <- list()
active_tab[['a_b']] <- F
active_tab[['a_only']] <- F

if(NROW(onc_enrich_report[['data']][['synleth']][['both_in_pair']]) > 0){
  sl_interactions[['a_b']] <- onc_enrich_report[['data']][['synleth']][['both_in_pair']] |>
    dplyr::filter(.data$prediction_percentile < 50) |>
    head(2500)

  active_tab[['a_b']] <- T

}

if(NROW(onc_enrich_report[['data']][['synleth']][['single_pair_member']]) > 0){
  sl_interactions[['a_only']] <- onc_enrich_report[['data']][['synleth']][['single_pair_member']] |>
    dplyr::filter(.data$prediction_percentile < 50) |>
    head(2500)

  if(active_tab[['a_b']] == F){
    active_tab[['a_only']] <- T
  }

}

Predicted synthetic lethality interactions {.tabset}

if(active_tab[['a_b']] == T){
  cat("")
  cat("##### Both pair members in query set {.active}")
  cat("")
}else{
  cat("")
  cat("##### Both pair members in query set")
  cat("")
}

sl_ab <- 
  crosstalk::SharedData$new(sl_interactions[['a_b']])

crosstalk::bscols(
  list(
    crosstalk::filter_select("gene_A", "Interactor A", sl_ab, ~gene_A),
    crosstalk::filter_select("gene_B", "Interactor B", sl_ab, ~gene_B),
    crosstalk::filter_slider("prediction_score", "Prediction score", sl_ab, ~prediction_score,
                             step = 0.025, min = 0.0, max = 0.45),
    crosstalk::filter_slider("prediction_percentile", "Prediction percentile", sl_ab, ~prediction_percentile,
                             min = 0.0, step = 2, max = 50)
  ),
  list(
    crosstalk::filter_slider("sequence_identity_pct", "Sequence identity (percent)", sl_ab, ~sequence_identity_pct,
                             min = 0, max = 100),
    crosstalk::filter_slider("family_size", "Gene family size", sl_ab, ~family_size)
  )
)

htmltools::br()

DT::datatable(
  sl_ab, 
  escape = F, 
  extensions=c("Buttons","Responsive"), 
  width = "100%",
  style = 'bootstrap',
  rownames = F,
  options=list(buttons = c('csv','excel'),
               pageLength = 10,
               bPaginate = T,
               dom = 'Bfrtip')
  ) |>
   DT::formatStyle("gene_A",
                  "prediction_percentile", 
                  color = "white", 
                  backgroundColor = DT::styleInterval(
                    onc_enrich_report[['config']][['synleth']][['breaks']],
                    onc_enrich_report[['config']][['synleth']][['colors']])
  ) |>
  DT::formatStyle("gene_B",
                  "prediction_percentile", 
                  color = "white", 
                  backgroundColor = DT::styleInterval(
                    onc_enrich_report[['config']][['synleth']][['breaks']],
                    onc_enrich_report[['config']][['synleth']][['colors']])
  )

cat('\n <ul><li>  <i> <span style="font-size: 105%; padding: 3px; background-color:#989898; color:white">&nbsp;&nbsp;<b>NO</b> genes in the queryset are involved in synthetic lethality interactions for which <b>BOTH</b> member pairs are part of the queryset.&nbsp;&nbsp; </span></i></li></ul>',sep='\n')
cat('\n')
cat('<br><br>')

if(active_tab[['a_only']] == T){
  cat("")
  cat("##### Single pair member in query set {.active}")
  cat("")
}else{
  cat("")
  cat("##### Single pair member in query set")
  cat("")
}

sl_a <- 
  crosstalk::SharedData$new(sl_interactions[['a_only']])


crosstalk::bscols(
  list(
    crosstalk::filter_select("gene_A", "Interactor A", sl_a, ~gene_A),
    crosstalk::filter_select("gene_B", "Interactor B", sl_a, ~gene_B),
    crosstalk::filter_slider("prediction_score", "Prediction score", sl_a, ~prediction_score,
                             step = 0.025, min = 0.0, max = 0.45),
    crosstalk::filter_slider("prediction_percentile", "Prediction percentile", sl_a, ~prediction_percentile,
                             min = 0.0, step = 2, max = 50)
  ),
  list(
    crosstalk::filter_slider("sequence_identity_pct", "Sequence identity (percent)", sl_a, ~sequence_identity_pct,
                             min = 0, max = 100),
    crosstalk::filter_slider("family_size", "Gene family size", sl_a, ~family_size)
  )
)

htmltools::br()

DT::datatable(
  sl_a, 
  escape = F, 
  extensions=c("Buttons","Responsive"), 
  width = "100%",
  style = 'bootstrap',
  rownames = F,
  options=list(buttons = c('csv','excel'),
               pageLength = 10,
               bPaginate = T,
               dom = 'Bfrtip')
  ) |>
   DT::formatStyle("gene_A",
                  "prediction_percentile", 
                  color = "white", 
                  backgroundColor = DT::styleInterval(
                    onc_enrich_report[['config']][['synleth']][['breaks']],
                    onc_enrich_report[['config']][['synleth']][['colors']])
  )

cat('\n <ul><li>  <i> <span style="font-size: 105%; padding: 3px; background-color:#989898; color:white">&nbsp;&nbsp;<b>NO</b> genes in the queryset are involved in prediced synthetic lethal interactions for which <b>ONLY</b> a single member pair is part of the queryset.&nbsp;&nbsp; </span></i></li></ul>',sep='\n')
cat('\n')
cat('<br><br>')

{.unlisted .unnumbered .toc-ignore}

Citation Note : If you use the output of the Synthetic lethality module of oncoEnrichR in your research, please cite the following resources and tools: