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RNA-seq-like Gene Centric Signature Reverse Search (RGCSRS)

Input gene: S1PR3

S1PR3 is not a landmark gene.

S1PR3 is not an originally inferred L1000 gene.

S1PR3 is a newly inferred (our model) gene.

More information about S1PR3 can be found at the Gene and Drug Landing Page Aggregator

Input cell line: All

This Appyter provides visualizations of the top 5% of RNA-seq-like signatures induced by CRISPR knockouts and chemical perturbagens. Signatures are computed from transformed data profiles from the LINCS L1000 data. The transformation was performed using a two-step model:

  1. A cycleGAN model was used to first predict the RNA-seq expression of the 978 L1000 landmark genes
  2. A fully connected neural network was used to extrapolate the predicted RNA-seq expression of the 978 landmark genes to a full set of 23,164 genes

Signatures were computed using the characteristic direction method (Clark et al., 2014), as implemented here.

Each gene was pre-queried across all available RNA-seq-like signatures, and the top signatures where a gene is up or down-regulated are returned for each gene.

CRISPR KO signatures

Volcano Plots

In the following volcano plot, each point represents a single CRISPR knockout signature. The x-position indicates the log2(fold change) of the expression of the chosen gene in the signature, while the y-position indicates the absolute value of the characteristic direction coefficient of the chosen gene.

Note that the fold change and characteristic direction coefficients of the gene are not necessarily in the same direction for each signature; this is because in cases where a gene is both up- and down-regulated between replicate samples, the characteristic direction method prioritizes the more consistent direction of movement, which may not be consistent with the fold change. To read more about the characteristic direction method, please refer to Clark et al., 2014.

Points with same-direction fold change and CD coefficient values are highlighted by coloring them blue (up-regulated) or red (down-regulated). Darker colored points indicate higher differential expression of the gene in the corresponding signature.

Drag the plot to pan around. Use the toolbar to the right of the plot to zoom, reset the plot view, or download the plot.

Tables

The tables below display the characteristic direction (CD) coefficients, fold change values, and log2(fold change) values correponding to the expression of the chosen gene in each CRIPSR KO signature.

The rank of the gene in the signature is determined by its fold change relative to the fold change of the other genes that are regulated in the same direction; if a gene is ranked 1 in a signature where the gene is up-regulated, that means that out of all genes up-regulated in the signature, the input gene had the highest fold change and was the most up-regulated.

While only the top 10 signatures for each direction are displayed, below each table is a link to download the top 50 signatures for each direction.

A link to the Enrichr analysis results of the top 20 unique perturbations from the top signatures that up or down-regulate the input gene can be found below each table as well.

Top CRISPR KO signatures where S1PR3 is up-regulated (based on fold change)
CD Coefficient Fold Change Log2(Fold Change) Rank in Signature KO Gene Cell Line Timepoint
Signature
XPR037_A375.311_96H_K24_FOSL1 0.0348 1.2237 0.291272 1297.0 FOSL1 A375.311 96h
XPR027_A375.311_96H_O09_VAV1 0.0357 1.2131 0.278680 961.0 VAV1 A375.311 96h
XPR020_AGS.311_96H_A08_MC4R 0.0379 1.1947 0.256590 980.0 MC4R AGS.311 96h
XPR030_HT29.311_96H_O07_SFRP1 0.0340 1.1847 0.244491 1721.0 SFRP1 HT29.311 96h
XPR014_A549.311_96H_D19_CFHR5 0.0341 1.1666 0.222312 1226.0 CFHR5 A549.311 96h
XPR026_A375.311_96H_H02_UBE2L3 0.0338 1.1643 0.219408 1268.0 UBE2L3 A375.311 96h
XPR030_U251MG.311_96H_E09_RAD51 0.0390 1.1490 0.200326 1125.0 RAD51 U251MG.311 96h
XPR022_A375.311_96H_M12_PTP4A1 0.0357 1.1474 0.198311 2022.0 PTP4A1 A375.311 96h
XPR032_A375.311_96H_P11_TWF2 0.0343 1.1455 0.195920 714.0 TWF2 A375.311 96h
XPR033_PC3.311B_96H_G08_NDUFB10 0.0378 1.1389 0.187607 2260.0 NDUFB10 PC3.311B 96h
Top CRISPR KO signatures where S1PR3 is down-regulated (based on fold change)
CD Coefficient Fold Change Log2(Fold Change) Rank in Signature KO Gene Cell Line Timepoint
Signature
XPRJJ002_A375_96H_N21_CBX2 -0.0396 0.7793 -0.359719 804.0 CBX2 A375 96h
XPR013_A549.311_96H_A13_C22ORF46 -0.0382 0.7928 -0.334986 1142.0 C22ORF46 A549.311 96h
XPR022_A375.311_96H_B07_RAB27A -0.0338 0.8153 -0.294592 1520.0 RAB27A A375.311 96h
XPR024_A375.311_96H_H11_SLPI -0.0411 0.8372 -0.256383 1101.0 SLPI A375.311 96h
XPR029_U251MG.311_96H_G09_LTB4R2 -0.0342 0.8472 -0.239269 1903.0 LTB4R2 U251MG.311 96h
XPR043_IPC298.311_96H_P14_HADH -0.0367 0.8497 -0.234985 1916.0 HADH IPC298.311 96h
XPR019_AGS.311_96H_B05_KCNK10 -0.0379 0.8530 -0.229318 1415.0 KCNK10 AGS.311 96h
XPR012_A375.311_96H_F10_BYSL -0.0347 0.8536 -0.228387 2328.0 BYSL A375.311 96h
XPR015_A375.311_96H_B06_DEPDC5 -0.0404 0.8576 -0.221625 1093.0 DEPDC5 A375.311 96h
XPR024_A375.311_96H_L19_SMARCAL1 -0.0352 0.8612 -0.215502 1368.0 SMARCAL1 A375.311 96h

Chemical perturbation signatures

Volcano Plots

In the following volcano plot, each point represents a single chemical perturbation signature. The x-position indicates the log2(fold change) of the expression of the chosen gene in the signature, while the y-position indicates the absolute value of the characteristic direction coefficient of the chosen gene.

Note that the fold change and characteristic direction coefficients of the gene are not necessarily in the same direction for each signature; this is because in cases where a gene is both up- and down-regulated between replicate samples, the characteristic direction method prioritizes the more consistent direction of movement, which may not be consistent with the fold change. To read more about the characteristic direction method, please refer to Clark et al., 2014.

Points with same-direction fold change and CD coefficient values are highlighted by coloring them blue (up-regulated) or red (down-regulated). Darker colored points indicate higher differential expression of the gene in the corresponding signature.

Drag the plot to pan around. Use the toolbar to the right of the plot to zoom, reset the plot view, or download the plot.

Tables

The tables below display the characteristic direction (CD) coefficients, fold change values, and log2(fold change) values correponding to the expression of the chosen gene in each chemical perturbation signature.

The rank of the gene in the signature is determined by its fold change relative to the fold change of the other genes that are regulated in the same direction; if a gene is ranked 1 in a signature where the gene is up-regulated, that means that out of all genes up-regulated in the signature, the input gene had the highest fold change and was the most up-regulated.

While only the top 10 signatures for each direction are displayed, below each table is a link to download the top 50 signatures for each direction.

A link to the Enrichr analysis results of the top 20 unique perturbations from the top signatures that up or down-regulate the input gene can be found below each table as well.

Top chemical perturbation signatures where S1PR3 is up-regulated (based on fold change)
CD Coefficient Fold Change Log2(Fold Change) Rank in Signature Perturbagen Dose Cell Line Timepoint
Signature
MOAR002_A375_24H_F16_trifluridine_10uM 0.0400 1.4008 0.486299 817.0 trifluridine 10uM A375 24h
CPC001_HCC515_6H_D01_ipratropium_10uM 0.0371 1.3676 0.451676 2007.0 ipratropium 10uM HCC515 6h
LJP006_HEPG2_24H_A21_HG-5-88-01_1.11uM 0.0427 1.3384 0.420491 1447.0 HG-5-88-01 1.11uM HEPG2 24h
CPC004_HCC515_6H_E04_fenoterol_10uM 0.0375 1.3227 0.403470 1508.0 fenoterol 10uM HCC515 6h
REP.A027_HA1E_24H_B23_thiomersal_0.125uM 0.0402 1.2498 0.321643 1557.0 thiomersal 0.125uM HA1E 24h
ASG002_JHH7_24H_G16_tandutinib_10uM 0.0377 1.2136 0.279247 888.0 tandutinib 10uM JHH7 24h
REP.A022_PC3_24H_E08_afloqualone_3.33uM 0.0393 1.2106 0.275778 1262.0 afloqualone 3.33uM PC3 24h
LTC002_HME1_3H_C10_PD-0325901_0.12uM 0.0380 1.2024 0.265865 2205.0 PD-0325901 0.12uM HME1 3h
MOAR012_A204_24H_A23_perzinfotel_3.33uM 0.0377 1.1929 0.254436 1614.0 perzinfotel 3.33uM A204 24h
CVD001_HEPG2_24H_F12_LY-2183240_2.5uM 0.0372 1.1599 0.214045 1304.0 LY-2183240 2.5uM HEPG2 24h
Top chemical perturbation signatures where S1PR3 is down-regulated (based on fold change)
CD Coefficient Fold Change Log2(Fold Change) Rank in Signature Perturbagen Dose Cell Line Timepoint
Signature
ERG021_PC3_24H_G18_wortmannin_0.04uM -0.0367 0.5250 -0.929485 694.0 wortmannin 0.04uM PC3 24h
LJP006_HEPG2_24H_J04_AZD-5438_0.37uM -0.0377 0.6116 -0.709369 1139.0 AZD-5438 0.37uM HEPG2 24h
LJP006_HEPG2_24H_C02_GSK-1059615_3.33uM -0.0378 0.6487 -0.624380 915.0 GSK-1059615 3.33uM HEPG2 24h
MOAR011_HCC95_24H_G24_batimastat_1.11uM -0.0410 0.6640 -0.590667 638.0 batimastat 1.11uM HCC95 24h
MOAR009_SNU407_24H_O11_L-778123_3.33uM -0.0396 0.6908 -0.533558 895.0 L-778123 3.33uM SNU407 24h
REP.B027_HA1E_24H_E12_digoxin_0.01uM -0.0426 0.7518 -0.411636 1099.0 digoxin 0.01uM HA1E 24h
CPC001_PC3_6H_A23_piretanide_10uM -0.0443 0.7634 -0.389537 1246.0 piretanide 10uM PC3 6h
LJP006_HA1E_24H_L10_WYE-125132_0.37uM -0.0374 0.7702 -0.376703 1660.0 WYE-125132 0.37uM HA1E 24h
LJP009_MCF7_24H_K09_GSK-1059615_1.11uM -0.0434 0.8141 -0.296647 1787.0 GSK-1059615 1.11uM MCF7 24h
LJP009_HA1E_24H_P14_KI-20227_3.33uM -0.0371 0.8184 -0.289205 1848.0 KI-20227 3.33uM HA1E 24h