Quantile-normalized transcriptomes from control and ligand-treated cell lines (level 3 data)

Ligands / cell lines assayed

In the Connectivity Map data, there are 16 ligands assayed in all 14 cell lines, and 300 ligands assayed in 8 cell lines.

EGF HGF INS IGF2 TGFA IGF1 FGF1 HBEGF IL6 IL4 IFNG BTC GDNF GAS6 TNF IL17A ctrl min.ctrl.ratio
breast_normal_MCF10A 119 62 62 62 62 62 59 61 60 59 60 60 61 60 62 60 196 0.6071429
breast_tumor_BT20 146 74 74 73 74 74 74 74 73 74 73 74 74 69 74 74 273 0.5347985
breast_tumor_HS578T 120 58 59 60 60 60 60 60 60 59 58 57 58 59 55 60 232 0.5172414
breast_tumor_MCF7 153 83 80 80 80 80 80 80 78 78 78 80 79 76 75 75 4389 0.0348599
breast_tumor_MDAMB231 120 58 60 60 60 60 60 60 60 60 59 58 59 59 56 60 251 0.4780876
breast_tumor_SKBR3 123 57 62 62 62 62 62 62 62 62 61 60 58 62 57 62 265 0.4641509
kidney_normal_HA1E 5 10 5 5 5 5 5 5 5 5 5 5 5 5 5 3 1135 0.0088106
large_intestine_tumor_HT29 5 10 5 5 4 4 5 4 5 4 5 4 4 4 5 3 2059 0.0048567
liver_tumor_HEPG2 6 12 6 6 6 6 6 6 6 6 6 6 5 6 6 3 780 0.0153846
lung_normal_HCC515 5 10 5 5 5 5 5 5 5 5 5 5 5 5 5 3 957 0.0104493
lung_tumor_A549 6 12 6 6 6 6 6 5 6 5 6 6 6 6 6 3 2847 0.0042150
prostate_tumor_PC3 5 7 5 5 4 4 5 5 4 5 5 5 3 4 5 5 4060 0.0017241
prostate_tumor_VCAP 6 12 6 6 6 6 6 6 6 6 6 6 6 6 6 4 5071 0.0023664
skin_tumor_A375 5 10 5 5 5 5 5 5 5 5 5 5 5 5 5 3 2264 0.0044170
Totals 824 475 440 440 439 439 438 438 435 433 432 431 428 426 422 418 24779 0.0332540

In a subset of cell lines, ligands were tested over a variety of doses and times (and EGF was especially rigorously assayed), while in most cell lines ligands were tested at a single concentration over two time points. Note that the number of control samples per cell type is much greater than the number of treatments.

Overall UMAP

Above are UMAP projections (from assayed genes) of all Connectivity Map ligand-treated and control data coloured by cell type.

UMAP for common ligands only

Zooming in to include only the 16 ligands assayed in all cell types and their plate-matched controls (coloured in black).

UMAP per cell line

Below are UMAP projections of ligand-treated and control samples for each cell type. Only the 16 ligands assayed in all cell types and their plate-matched controls (coloured in black) are included.

So it seems the plate effect is strong in this data. Might consider using the plate-based Z-scores from Cmap level 5 instead of the quantile normalized transcriptomes from level 3 that are shown here.

UMAP per ligand treatment

Looks like transcriptomes are entirely delineated by cell type from the ligand perspective.

Robust Z-scores of differences in cell line transcriptomes following ligand treatment (level 4 data)

EGF HGF INS IGF2 TGFA IGF1 FGF1 HBEGF IL6 IL4 IFNG BTC GDNF GAS6 TNF IL17A Total
breast_normal_MCF10A 119 62 62 62 62 62 59 61 60 59 60 60 61 60 62 60 1031
breast_tumor_BT20 146 74 74 73 74 74 74 74 73 74 73 74 74 69 74 74 1248
breast_tumor_HS578T 120 58 59 60 60 60 60 60 60 59 58 57 58 59 55 60 1003
breast_tumor_MCF7 153 83 80 80 80 80 80 80 78 78 78 80 79 76 75 75 1335
breast_tumor_MDAMB231 120 58 60 60 60 60 60 60 60 60 59 58 59 59 56 60 1009
breast_tumor_SKBR3 123 57 62 62 62 62 62 62 62 62 61 60 58 62 57 62 1036
kidney_normal_HA1E 5 10 5 5 5 5 5 5 5 5 5 5 5 5 5 3 83
large_intestine_tumor_HT29 5 10 5 5 4 4 5 4 5 4 5 4 4 4 5 3 76
liver_tumor_HEPG2 6 12 6 6 6 6 6 6 6 6 6 6 5 6 6 3 98
lung_normal_HCC515 5 10 5 5 5 5 5 5 5 5 5 5 5 5 5 3 83
lung_tumor_A549 6 12 6 6 6 6 6 5 6 5 6 6 6 6 6 3 97
prostate_tumor_PC3 5 7 5 5 4 4 5 5 4 5 5 5 3 4 5 5 76
prostate_tumor_VCAP 6 12 6 6 6 6 6 6 6 6 6 6 6 6 6 4 100
skin_tumor_A375 5 10 5 5 5 5 5 5 5 5 5 5 5 5 5 3 83
Total 824 475 440 440 439 439 438 438 435 433 432 431 428 426 422 418 7358

Overall UMAP

Last line are UMAP projections using all (including inferred) gene Z-scores. This was included to see whether adding inferred genes improved the structure, but that doesn’t seem to be the case.

Above are UMAP projections (from assayed genes) of all Connectivity Map ligand-treated and control data coloured by cell type.

UMAP per cell line

Below are UMAP projections of ligand-treated and control samples for each cell type. Only the 16 ligands assayed in all cell types and their plate-matched controls (coloured in black) are included.

UMAP per ligand treatment

UMAP per cell line

Rerunning these using all genes (including inferred).

UMAP per ligand treatment

Replicate-collapsed robust Z-scores of differences in cell line transcriptomes following ligand treatment (level 5 data)

Ligands / cell lines assayed

In the Connectivity Map data, there are 16 ligands assayed in all 14 cell lines, and 300 ligands assayed in 8 cell lines.

EGF HGF INS IGF2 TGFA IGF1 FGF1 HBEGF IL6 IL4 IFNG BTC GDNF GAS6 TNF IL17A
breast_normal_MCF10A 28 14 14 14 14 14 14 14 14 14 14 14 14 14 14 14
breast_tumor_BT20 32 16 16 16 16 16 16 16 16 16 16 16 16 16 16 16
breast_tumor_HS578T 28 14 14 14 14 14 14 14 14 14 14 14 14 14 14 14
breast_tumor_MCF7 34 19 18 18 18 18 18 18 18 18 18 18 18 18 18 17
breast_tumor_MDAMB231 28 14 14 14 14 14 14 14 14 14 14 14 14 14 14 14
breast_tumor_SKBR3 28 14 14 14 14 14 14 14 14 14 14 14 14 14 14 14
kidney_normal_HA1E 2 3 2 2 2 2 2 2 2 2 2 2 2 2 2 1
large_intestine_tumor_HT29 2 3 2 2 2 2 2 2 2 2 2 2 2 2 2 1
liver_tumor_HEPG2 2 3 2 2 2 2 2 2 2 2 2 2 2 2 2 1
lung_normal_HCC515 2 3 2 2 2 2 2 2 2 2 2 2 2 2 2 1
lung_tumor_A549 2 3 2 2 2 2 2 2 2 2 2 2 2 2 2 1
prostate_tumor_PC3 2 4 2 2 2 2 2 2 2 2 2 2 2 2 2 2
prostate_tumor_VCAP 3 5 3 3 3 3 3 3 3 3 3 3 3 3 3 2
skin_tumor_A375 2 3 2 2 2 2 2 2 2 2 2 2 2 2 2 1
Totals 195 118 107 107 107 107 107 107 107 107 107 107 107 107 107 99

In a subset of cell lines, ligands were tested over a variety of doses and times (and EGF was especially rigorously assayed), while in most cell lines ligands were tested at a single concentration over two time points. Note that these data (level 5) are replicate-aggregated Z-scores, so each reported assay represents multiple replicates.

Overall UMAP

Above are UMAP projections (from assayed genes) of all Connectivity Map ligand-treated and control data coloured by cell type.

UMAP per cell line

Below are UMAP projections of ligand-treated and control samples for each cell type. Only the 16 ligands assayed in all cell types and their plate-matched controls (coloured in black) are included.

UMAP per ligand treatment