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JUMP-Target

The JUMP-Target set of perturbations comprises three lists of perturbations

  1. JUMP-Target-Compound – a list of compounds with diverse targets. See also JUMP-MOA for a similar compound set.
  2. JUMP-Target-ORF – a list of ORF sequences corresponding to genes that are targets of compounds from JUMP-Target-Compound.
  3. JUMP-Target-CRISPR – a list of sgRNA sequences corresponding to genes that are targets of compounds from JUMP-Target-Compound.

Both JUMP-Target-ORF and JUMP-Target-CRISPR have sgRNAs and ORFs corresponding to a set of 160 genes, each of which are targets of compounds in JUMP-Target-Compound. JUMP-Target-ORF has perturbations for an additional set of 15 genes that serve as negative controls (below).

Each of the 3 lists fit on a single 384-well plate; the suggested plate layouts are provided (below).

The target annotations were obtained from https://clue.io/repurposing.

This resource was created through the JUMP-Cell Painting Consortium.

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JUMP-Target-Compound

There are 301 compounds in total, of which 46 are included as controls serving different goals

  1. poscon_orf: compounds that correlate strongly with (overexpressed) genes in previous Cell Painting experiments. There are 6 such compounds, and their corresponding 3 genes are included in JUMP-Target-ORF and JUMP-Target-CRISPR
  2. poscon_cp: compounds with a strong association with the genes that they target, according to ChemicalProbes.org. There are 26 such compounds, and their corresponding 13 genes are included in JUMP-Target-ORF and JUMP-Target-CRISPR.
  3. poscon_diverse: pairs of compounds that are strongly correlated to each other, and weakly correlated to other poscon_diverse pairs, in previous Cell Painting experiments. There are 7 such pairs, so 14 compounds in total.
  4. negcon: DMSO is the negative control.

The recommended concentration for these compounds is 5 uM.

There are

The company Specs has assembled the compounds for purchase; for info contact tamara.baptist@specs.net

Files

JUMP-Target-1_compound_metadata.tsv JUMP-Target-2_compound_metadata.tsv

ColumnDescription
pert_inameCompound name
pubchem_cidPubChem ID e.g. 72716071
targetGene target
pert_typePerturbation type – trt: treatment, control: one of the 3 controls
control_typeControl type – poscon_orf, poscon_cp, or poscon_diverse
smilesSimplified molecular-input line-entry system (SMILES) string
InChIInternational Chemical Identifier corresponding to smiles
InChIKeyInChIKey generated from InChI

smiles was standardized using JUMP-CP Standardizer. See https://github.com/jump-cellpainting/JUMP-Target/pull/34 for details about the standardization.

JUMP-Target-1_compound_platemap.tsv JUMP-Target-2_compound_platemap.tsv

ColumnDescription
well_positionWell position
broad_sampleCompound ID in Broad Institute's compound management database
solventSolvent (always DMSO)

Broad internal notes

JUMP-Target-CRISPR

There are 335 sgRNAs (corresponding to 175 genes) in total, of which 88 sgRNAs are included as controls serving different goals

  1. poscon_orf: the corresponding genes targets of the poscon_orf compounds. Total: 3 genes x 2 sgRNAs per gene (except for one gene which has a single sgRNA) = 5 sgRNAs.
  2. poscon_cp: the corresponding genes targets of the poscon_cp compounds. Total: 13 genes x 2 sgRNAs per gene (except for one gene which has a single sgRNA) = 25 sgRNAs.
  3. poscon_diverse: the corresponding genes targets of the poscon_diverse compounds. Total: 14 genes x 2 sgRNAs per gene = 28 sgRNAs.
  4. negcon: 30 unique sgRNAs that serve as negative controls because they are either non-targeting (NO_SITE) or target intergenic region (ONE_INTERGENIC_SITE). negcon sgRNAs have an additional annotation e.g. NO_SITE (5 zeros). The number of zeros indicates how deep into the "threat matrix" a particular sgRNA makes it before a single match is found. An sgRNA negcon with higher number of zeros is less likely to have off-target effects and therefore may be a better negative control.

There are

Files

JUMP-Target-1_crispr_metadata.tsv

ColumnDescription
broad_samplesgRNA id in Broad Institute's Genetic Perturbation Platform database
geneGene targeted by the sgRNA
pert_typePerturbation type – trt: treatment, control: one of the 4 controls
control_typeControl type – negcon, poscon_orf, poscon_cp, or poscon_diverse
target_sequencesgRNA sequence
negcon_control_typeNegative control type – NO_SITE or ONE_INTERGENIC_SITE

JUMP-Target-1_crispr_platemap.tsv

ColumnDescription
well_positionWell position
broad_samplesgRNA id in Broad Institute's Genetic Perturbation Platform database

JUMP-Target-ORF

There are 175 ORFs (corresponding to 175 genes) in total, of which 45 ORFs (corresponding to 45 genes) are included as controls serving different goals and 130 genes are represented in duplicate on the plate.

All genes have a single corresponding ORF

  1. poscon_orf: the corresponding genes targets of the poscon_orf compounds. Total: 3 genes.
  2. poscon_cp: the corresponding genes targets of the poscon_cp compounds. Total: 13 genes.
  3. poscon_diverse: the corresponding genes targets of the poscon_diverse compounds. Total: 14 genes.
  4. negcon: genes that have had weak signatures in previous Cell Painting overexpression experiments. Total: 15 genes.

There are

Files

JUMP-Target-1_orf_metadata.tsv

ColumnDescription
broad_sampleORF id in Broad Institute's Genetic Perturbation Platform database
geneGene overexpressed by the ORF
pert_typePerturbation type – trt: treatment, control: one of the 4 controls
control_typeControl type – negcon, poscon_orf, poscon_cp, or poscon_diverse

JUMP-Target-1_orf_platemap.tsv

ColumnDescription
well_positionWell position
broad_sampleORF id in Broad Institute's Genetic Perturbation Platform database

Compound and gene selection

The list of compounds were derived from Broad's Drug Repurposing Hub dataset, a curated and annotated collection of FDA-approved drugs, clinical trial drugs, and pre-clinical tool compounds. The genes perturbed by genetic perturbations were chosen because they are the annotated targets of the compounds. The Repurposing Hub compounds were filtered using the following criteria:

  1. The compounds should target genes that belong to diverse gene families. This is because the ideal methods would work well for many different biological pathways, not just a few that are well-characterized and/or easy to predict.
  2. Each gene should be targeted by at least two compounds so that gene-compound matching and compound-compound matching can both be performed using the dataset.
  3. The constraint that each compound should target only a single gene, was considered. However, this criterion is difficult to achieve due to polypharmacology, which is the property for compounds to bind and impact many different gene products in the cell; this is especially common for protein kinase inhibitors in the dataset. Instead, only the so-called “historical compounds” listed in the Chemical Probes Portal, comprising compounds that are known to be quite non-selective (or not sufficiently potent) compared with other available chemical probes, were filtered out.
  4. Three types of positive control compounds and the genes that they target were selected. (Compound positive controls, CRISPR positive controls, and ORF positive controls).
  5. To ensure that the compounds and genes selected were available for performing experiments, compounds that were unavailable for purchase from at least one of four compound vendors (Sigma, SelleckChem, Tocris, and MedChemEx) and genes for which genetic reagents were unavailable from Broad's GPP portal were filtered out.
  6. Compounds that belong to DEA's list of controlled substances or OPCW's list of chemical weapons precursors were also excluded.

Positive control compounds

Based on our experiments with the Target-1 compounds plates, we have identified a list of eight compounds (and also a subset of four compounds) with maximally diverse phenotypes.

pert_inameInChIKeyVendor URLclue.io URL
AMG900IVUGFMLRJOCGAS-UHFFFAOYSA-Nhttps://www.selleckchem.com/products/amg-900.htmlhttps://clue.io/repurposing-app?q=Name:AMG900
NVS-PAK1-1OINGHOPGNMYCAB-INIZCTEOSA-Nhttps://www.medchemexpress.com/NVS-PAK1-1.htmlhttps://clue.io/repurposing-app?q=Name:NVS-PAK1-1
dexamethasoneUREBDLICKHMUKA-CXSFZGCWSA-Nhttps://www.tocris.com/products/dexamethasone_1126https://clue.io/repurposing-app?q=Name:dexamethasone
LY2109761IHLVSLOZUHKNMQ-UHFFFAOYSA-Nhttps://www.selleckchem.com/products/ly2109761.htmlhttps://clue.io/repurposing-app?q=Name:LY2109761
FK-866KPBNHDGDUADAGP-VAWYXSNFSA-Nhttps://www.selleckchem.com/products/apo866-fk866.htmlhttps://clue.io/repurposing-app?q=Name:FK-866
quinidineLOUPRKONTZGTKE-LHHVKLHASA-Nhttps://www.medchemexpress.com/Quinidine.htmlhttps://clue.io/repurposing-app?q=Name:quinidine
TC-S-7004CQKBSRPVZZLCJE-UHFFFAOYSA-Nhttps://www.tocris.com/products/tc-s-7004_5088https://clue.io/repurposing-app?q=Name:TC-S-7004
aloxistatinSRVFFFJZQVENJC-IHRRRGAJSA-Nhttps://www.medchemexpress.com/Aloxistatin.htmlhttps://clue.io/repurposing-app?q=Name:aloxistatin

Compound names in bold is the subset of four compounds.

Layout

Our recommendation is to have at least four replicates of the eight (or four) compounds spread across the plate. If such a layout is not possible, then we recommend the following for a 384-well plate.

pert_inamewell_position
AMG900B1, J1, F24, N24
NVS-PAK1-1F1, N1, B24, J24
dexamethasoneC1, K1, G24, O24
LY2109761E1, M1, A24, I24
FK-866D1, L1, H24, P24
quinidineG1, O1, C24, K24
TC-S-7004H1, P1, D24, L24
aloxistatinA1, I1, E24, M24

For a 1536-well plate, the layout is similar, but in four quadrants.

Control mappings

poscon_diverse

IDpairtarget_geneInChIKeybroad_compound_idbroad_orf_idbroad_crispr_id_1broad_crispr_id_2
poscon_diverse-pair0-10RETXKFTZKGMDDZMJIBRD-K07881437-001-03-8ccsbBroad304_14827BRDN0001058343BRDN0001058011
poscon_diverse-pair0-20TUBBMTJHLONVHHPNSIBRD-K23363278-001-02-1ccsbBroad304_05206BRDN0001489809BRDN0001488241
poscon_diverse-pair1-11HSP90AA1RVAQIUULWULRNWBRD-K38852836-001-04-9ccsbBroad304_06412BRDN0001488886BRDN0001483257
poscon_diverse-pair1-21PIK3CGCWHUFRVAEUJCEFBRD-K42191735-001-08-7ccsbBroad304_14762BRDN0001065162BRDN0001065152
poscon_diverse-pair2-12NAMPTKPBNHDGDUADAGPBRD-K58550667-001-08-7ccsbBroad304_07557BRDN0001484730BRDN0001481327
poscon_diverse-pair2-22AKT1AFJRDFWMXUECEWBRD-K25412176-001-01-9ccsbBroad304_14538BRDN0001054985BRDN0000562836
poscon_diverse-pair3-13KRASDHMTURDWPRKSOABRD-K41599323-001-02-3ccsbBroad304_16173BRDN0001054815BRDN0000563627
poscon_diverse-pair3-23PAK4AYCPARAPKDAOENBRD-K37764012-001-03-3ccsbBroad304_02392BRDN0001145608BRDN0001147629
poscon_diverse-pair4-14DNMT3ANMUSYJAQQFHJEWBRD-K03406345-001-21-1ccsbBroad304_00454BRDN0001066838BRDN0001066751
poscon_diverse-pair4-24IMPDH1WYWHKKSPHMUBEBBRD-K49350383-001-13-7ccsbBroad304_06451BRDN0001489452BRDN0001488805
poscon_diverse-pair5-15CDK7HUXYBQXJVXOMKXBRD-K64800655-001-09-0ccsbBroad304_00280BRDN0001162216BRDN0001147450
poscon_diverse-pair5-25PLK1XQVVPGYIWAGRNIBRD-K64890080-001-02-1ccsbBroad304_14770BRDN0001144995BRDN0001054037
poscon_diverse-pair6-16CHEK2IAYGCINLNONXHYBRD-K86525559-001-07-8ccsbBroad304_14989BRDN0000585854BRDN0001145610
poscon_diverse-pair6-26GABRB2ALBKMJDFBZVHAKBRD-K33882852-003-02-8ccsbBroad304_00607BRDN0001486784BRDN0001482741

Other poscons

IDtarget_genebroad_compound_id_1broad_compound_id_2broad_orf_idbroad_crispr_id_1broad_crispr_id_2
poscon_cp-00AURKBBRD-K21728777-001-02-3BRD-K55966568-001-09-6ccsbBroad304_14932BRDN0001054845BRDN0000562944
poscon_cp-01BRD4BRD-K13094524-001-04-2BRD-K12502280-001-11-4ccsbBroad304_11738BRDN0000733514BRDN0001146786
poscon_cp-02CLK1BRD-K66430217-001-03-8BRD-K97072811-001-11-4ccsbBroad304_00326BRDN0001147209BRDN0001146512
poscon_cp-03DYRK1BBRD-K89517477-001-01-4BRD-K80935598-001-01-1ccsbBroad304_14931BRDN0001149482BRDN0001149418
poscon_cp-04ERBB2BRD-K76908866-001-07-6BRD-K61642990-001-01-0ccsbBroad304_14631BRDN0001148320BRDN0000579738
poscon_cp-05EZH2BRD-K91535048-001-01-2BRD-K26989966-001-04-3ccsbBroad304_00526BRDN0001057455
poscon_cp-06FLT3BRD-K90747162-001-01-4BRD-K91283740-003-01-6ccsbBroad304_14644BRDN0001145324BRDN0001149376
poscon_cp-07HDAC3BRD-K61688984-001-02-9BRD-K61397605-001-01-8ccsbBroad304_07311BRDN0000582721BRDN0000733096
poscon_cp-08IGF1RBRD-K15179513-001-04-2BRD-K24696047-001-02-3ccsbBroad304_14671BRDN0001065819BRDN0001065728
poscon_cp-09JAK1BRD-K16803204-001-01-6BRD-K53972329-001-01-3ccsbBroad304_14679BRDN0001065674BRDN0001065858
poscon_cp-10METBRD-K73319509-001-08-0BRD-K19477839-001-07-6ccsbBroad304_14696BRDN0000734703BRDN0001065558
poscon_cp-11PAK1BRD-K19333160-001-01-3BRD-K28132190-001-02-0ccsbBroad304_01144BRDN0001145958BRDN0001147867
poscon_cp-12USP1BRD-K93942811-001-01-3BRD-K81197548-003-01-4ccsbBroad304_01760BRDN0001487607BRDN0001484218
poscon_orf-00BRAFBRD-K73789395-001-09-9BRD-K62810658-001-11-4ccsbBroad304_16175BRDN0001054801BRDN0000562882
poscon_orf-01CDK2BRD-K50836978-001-03-3BRD-K07762753-001-05-1ccsbBroad304_14572BRDN0001147786BRDN0001148950
poscon_orf-02MAPK14BRD-K54330070-001-19-6BRD-A37704979-001-12-3ccsbBroad304_00371BRDN0001148417