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Series GSE131325 Query DataSets for GSE131325
Status Public on Nov 08, 2022
Title Identification of drugs in leukaemia differentiation therapy by network pharmacology
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Acute leukaemias differ from their normal haematopoietic counterparts in their inability to differentiate. This phenomenon is thought to be the result of aberrant transcriptional reprogramming involving transcription factors (TFs). Here we leveraged on Mogrify, a network-based algorithm for predicting reprogramming factors, to identify TFs and their gene regulatory networks that drive ATRA-induced differentiation of the acute promyelocytic leukaemia (APL) cell line NB4. We further integrated the detected TF regulatory networks with the Connectivity Map (CMAP) repository and recovered small molecule compounds which induce similar transcriptional changes. Our method outperformed standard approaches, retrieving ATRA as the top hit. Of the other drug hits, dimaprit and mebendazole enhanced ATRA-mediated differentiation in both parental NB4 and ATRA-resistant NB4-MR2 cells. Thus, we provide a proof-of-principle of our network-based computational platform for drug discovery and repositioning in leukaemia differentiation therapy, which can be extended to other dysregulated disease states.
Overall design 33 NB4 APL samples consisting of No Treatment(basal=3), ATRA (treatment=15) and DMSO (control=15) conditions in 5 time points 4h, 12h, 24h, 72h and 120h in 3 biological replicates. Each biological replicate was further subjected to paired-end RNA-Seq in 2 technical replicates.
Contributor(s) Christodoulou EG, Lee LM, Lee KL, Giuseppe Petretto E, Llewllyn Rackham OJ, Ong ST, Shyamsunder P, Chen BJ, Fung TK, So WC, Wong GC
Citation(s) 36271030
Submission date May 16, 2019
Last update date Nov 08, 2022
Contact name Eleni G. Christodoulou
Phone +65 87420979
Organization name Duke-NUS Medical School
Street address 8 College Road
City Sinagpore
ZIP/Postal code 169857
Country Singapore
Platforms (1)
GPL21290 Illumina HiSeq 3000 (Homo sapiens)
Samples (33)
GSM3769167 NB4_0h_notreatment_2
GSM3769168 NB4_0h_notreatment_4
GSM3769169 NB4_0h_notreatment_5
BioProject PRJNA543254
SRA SRP198623

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Supplementary file Size Download File type/resource
GSE131325_RNAseq_full_all.counts.txt.gz 9.8 Mb (ftp)(http) TXT
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Raw data are available in SRA
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