Predicting Compounds that Can Reverse VEN/AZA-Resistant Signatures Identified from the UHG Project

Analysis Overview

• Specimens compared The R specimens have been confirmed by Clay/Maura/Austin in their 5/6/2020 email exchanges:
  • M01: 1526, 1556, 1273 (R) vs. 1387, 1308, 1466 (S)
  • M45: 1325 & 1283 (R) vs. 1258, 1285, 1456 (S)
• Input data: Gene lists generated by Austin stored in release1.1_20200416/20200505_NR_vs_R_Gene_Lists

##  [1] "M01_all_blasts_Up_in_R.tsv"       "M01_all_blasts_Up_in_S.tsv"      
##  [3] "M01_CMP-like_blasts_Up_in_R.tsv"  "M01_CMP-like_blasts_Up_in_S.tsv" 
##  [5] "M01_monocytic_blasts_Up_in_R.tsv" "M01_monocytic_blasts_Up_in_S.tsv"
##  [7] "M01_primitive_blasts_Up_in_R.tsv" "M01_primitive_blasts_Up_in_S.tsv"
##  [9] "M45_all_blasts_Up_in_R.tsv"       "M45_all_blasts_Up_in_S.tsv"      
## [11] "M45_CMP-like_blasts_Up_in_R.tsv"  "M45_CMP-like_blasts_Up_in_S.tsv" 
## [13] "M45_monocytic_blasts_Up_in_R.tsv" "M45_monocytic_blasts_Up_in_S.tsv"
## [15] "M45_primitive_blasts_Up_in_R.tsv" "M45_primitive_blasts_Up_in_S.tsv"

• CLUE Analysis: For each subpopulation (e.g. M45_CMP-like), the top 150 Up/Dn (limited by capacity of the CLUE software) genes were isolated from the lists and uploaded to the CLUE web tool. CLUE automaticlly performs cloud computing for each upload. When complete, “detailed analysis” results were choosen, and the reults table were downloaded as .txt files to local drive for further processing

## [1] "UHG_CITEseq_20200505_R_M01_all_blasts_clue_all.txt"      
## [2] "UHG_CITEseq_20200505_R_M01_primitive_blasts_clue_all.txt"
## [3] "UHG_CITEseq_20200505_R_M45_CMP-like_blasts_clue_all.txt" 
## [4] "UHG_CITEseq_20200505_R_M45_monocytic_blasts_clue_all.txt"

• Results filtration and visualization in R: For each perturbagen subtype (cp:compounds, kd:knockdown, oe:overexpressioon, cc:compound class), items with a connectivity score of <= -90 or >= 90 were isolated for visulization.
  
• Interpretation: In general, items with connectivity scores of -90 or lower are strong candidates for further study, i.e. are predicted to have the ability to reverse VEN/AZA-resistant signatures.
  
• More read:
  • The original paper
    
  • CLUE wikipedia

Analysis Results

R_M01_all_blasts

R_M01_primitive_blasts

R_M45_CMP-like_blasts

R_M45_monocytic_blasts

Overlapped drugs

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