REAGENT or RESOURCE	SOURCE	IDENTIFIER
Chemicals, peptides, and recombinant proteins
DMSO	Sigma	Cat# D8418
Sorafenib	Selleckchem	Cat# S7397
Puromycin	Sigma	Cat# P8833
Crystal violet powder	Sigma	Cat# C0075
Polybrene	Sigma	Cat# 107689
DMEM high glucose	Sigma	Cat# D5671
L-Glutamine	Sigma	Cat# G7513
Penicillin-Streptomycin	Sigma	Cat# P4333
10 × Trypsin/EDTA	Sigma	Cat# T4174
FBS	Sigma	Cat# F7524
PBS	Sigma	Cat# D8537
Opti-MEM	Gibco	Cat# 51985034
FuGENE	Promega	Cat# E2311
RNase A	Qiagen	Cat# 19101
Buffer P1	Qiagen	Cat# 19051
Recombinant Proteinase K solution (20 mg/mL)	Thermo Fisher Scientific	Cat# AM2546
Critical commercial assays
miRNeasy Mini kit	Qiagen	Cat# 217084
RNA analysis kit	Labgene	Cat# DNF4710500/4720500
Quant-itTM RiboGreen RNA assay Kit	Thermo Fisher Scientific	Cat# R11490
TruSeq stranded mRNA Library Prep Kit	Illumina	Cat# 20020594
HiSeq SBS kit V4	Illumina	Cat# FC-401-4002
Hiseq TruSeq SR Cluster Kit v3-cbot-HS	Illumina	Cat# GD-401-3001
QIAquick gel extraction kit	Qiagen	Cat# 28706
QIAquick PCR purification kit	Qiagen	Cat# 28104
NGS Prep Kit	CELLECTA	Cat# LNGS-120
Deposited data
RNA-sequencing data on Sorafenib-resistant cell lines	This paper	GEO: GSE117116
Synthetic lethal barcode sequencing data	This paper	GEO: GSE158458
Experimental models: Cell lines
Huh7	University Hospital Basel	N/A
HepG2	ATCC	Cat# HB-8065
Hep3B	ATCC	Cat# HB-8064
HLE	University Hospital Basel	N/A
SNU398	ATCC	Cat# CRL-2233
SNU449	ATCC	Cat# CRL-2234
SNU182	ATCC	Cat# CRL-2235
SNU475	ATCC	Cat# CRL-2236
SNU387	ATCC	Cat# CRL-2237
SNU423	ATCC	Cat# CRL-2238
PLC/PRF/75	ATCC	Cat# CRL-8024
Huh1	University Hospital Basel	N/A
WRL68	ATCC	Cat# CL-48
Huh6	University Hospital Basel	N/A
HEK-293T	ATCC	Cat# CRL-3216
Recombinant DNA
pMD2.G	Didier Trono Lab	Addgene Cat# 12259
pMDLg/pRRE	Didier Trono Lab	Addgene Cat# 12251
pRSV-Rev	Didier Trono Lab	Addgene Cat# 12253
Pooled lentiviral shRNA library	CELLECTA	Cat# HGW-M1-P2
Software and algorithms
FastQC	N/A	https://www.bioinformatics.babraham.ac.uk/projects/fastqc/
R Development Core	N/A	https://www.r-project.org/
Adobe Illustrator	Adobe	N/A
Prism 9	GraphPad	N/A
Other
12-well plate	Milian	Cat# 353043
24-well plate	Milian	Cat# 353047
T75 flask	Milian	Cat# 353136
T175 flask	Milian	Cat# 353112
0.45 μm syringe filter	Sigma	Cat# SLHV033R
15 mL tube	Sarstedt	Cat# 62.554.502
50 mL tube	Sarstedt	Cat# 62.547.254
Cryotube	Sarstedt	Cat# 72.380.007
Centrifuge	Eppendorf	5702
Cell-IQ	CM Technologies	N/A