Key Resources Table

REAGENT or RESOURCE	SOURCE	IDENTIFIER
Chemicals, Peptides, and Recombinant Proteins
Buffer TCL	QIAGEN	Cat# 1031576
Tetramethylammonium chloride (TMAC)	RSA Corporation	Cat# 344
Puromycin	Sigma-Aldrich	Cat# P9620
SAPE	Lifetech	Cat# S21388
DMEM	Fisher Scientific	Cat# MT-10-017-CV
RPMI1640 Medium	Mediatech	Cat# 10040CV
100X penicillin-streptomycin-glutamine	Invitrogen	Cat# 10378-016
Fetal bovine serum (FBS)	Sigma-Aldrich	Cat# F4135
16% (wt/vol) Paraformaldehyde (PFA), methanol free	Electron Microscopy Sciences	Cat# 15710-S
HBSS (10×; Invitrogen)	Invitrogen	Cat# 14065-056
Triton X-100	Sigma-Aldrich	Cat# T8787
Sodium bicarbonate	HyClone	Cat# SH30033.01
Methanol	VMR	Cat# BDH1135
MitoTracker Deep Red	Invitrogen	Cat# M22426
Wheat-germ agglutinin/Alexa Fluor 555 conjugate	Invitrogen	Cat# W32464
Phalloidin/Alexa Fluor 568 conjugate	Invitrogen	Cat# A12380
Concanavalin A/Alexa Fluor 488 conjugate	Invitrogen	Cat# C11252
Hoechst 33342	Invitrogen	Cat# H3570
SYTO 14 green fluorescent nucleic acid stain	Invitrogen	Cat# S7576
DMSO	Fisher Chemical	Cat# D128-500
Critical Commercial Assays
384 TurboCapture Kit	QIAGEN	Cat# 72271
HotStarTaq Kit	QIAGEN	Cat# 203209
M-MLV Reverse Transcriptase Kit	Promega	Cat# M1705
Taq Ligase Kit	NEB	Cat# M0208L
MagPlex Microspheres	Luminex	N/A
Cell Titer Glo	Promega	Cat#G7573
Deposited Data
L1000 dataset (∼1.3M profiles)	https://doi.org/10.1016/j.cell.2017.10.049	https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE92742
Auxiliary datasets and metadata	https://doi.org/10.1016/j.cell.2017.10.049	https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE92742
L1000 assay probes and analyte mappings	https://doi.org/10.1016/j.cell.2017.10.049	https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GPL20573
L1000 profiles	This paper	https://doi.org/10.6084/m9.figshare.13181966.v2
Cell Painting images	This paper	Image data resource accession number idr0125
Cell Painting profiles	This paper	https://doi.org/10.5281/zenodo.5008187
Experimental Models: Cell Lines
MCF7 (Cancer cell line; Breast; Female)	ATCC	HTB-22
A549 (Cancer cell line; Lung; Male)	ATCC	CCL-185
U2OS (Cancer cell line; Bone; Female)	ATCC	HTB-96
Oligonucleotides
LUA sequences	IDT	https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GPL20573
L1000 probe pairs	IDT	https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GPL20573
T7 biotinylated primer: /5Biosg/TAATACGACTCACTATAGGG	IDT	N/A
T3 primer: CAATTAACCCTCACTAAAGG	IDT	N/A
Software and Algorithms
Reprodicible analysis repository	https://github.com/broadinstitute/lincs-profiling-complementarity	https://doi.org/10.5281/zenodo.6522802
LINCS Cell Painting image-based profiling pipeline	https://github.com/broadinstitute/lincs-cell-painting	https://doi.org/10.5281/zenodo.5008187
CellProfiler	https://github.com/CellProfiler/CellProfiler	v2.3.1
cytominer-database	https://github.com/cytomining/cytominer-database	v0.3.3
pycytominer	https://github.com/cytomining/pycytominer	Github Hash: 4f37e019918256111933aed4e3b9afb50055b4a1
pandas	McKinney et al. 2010	v1.2
scikit-learn	Pedregosa et al. 2011	v0.24.2
cmapPy	Enache et al. 2018	v4.0.1
GO.db	Carlson 2017a	v3.14.0
org.Hs.eg.db	Carlson 2017b	v3.14.0
topGO	Alexa et al. 2017	v2.46.0
python	Van Rossum and Drake 2009	v3.9.1
R	R Core Team 2021	v3.5.1
ggplot2	Wickham 2016	v3.3.0
anaconda	Anaconda Inc. 2021	v4.10.3
Other
Detailed L1000 assay protocol	https://doi.org/10.1016/j.cell.2017.10.049	https://clue.io/sop-L1000.pdf
Detailed cell culture protocols	https://doi.org/10.1016/j.cell.2017.10.049	https://clue.io/sop-cell.pdf
Detailed Cell Painting protocol	https://www.nature.com/articles/nprot.2016.105	Cell Painting protocol v2 (Bray et al.)