GRB2

growth factor receptor bound protein 2

Dependent Cell Lines

CRISPR: 576/689 COMMON ESSENTIAL

RNAi: 39/708

Dependency Score

Dependent Cell Line: A cell line is considered dependent if it has a probability of dependency greater than 0.5.
Probability of Dependency: Probabilities of dependency are calculated for each gene score in a cell line as the probability that score arises from the distribution of essential gene scores rather than nonessential gene scores. See here for details.
Gene Effect: Outcome from DEMETER2 or CERES. A lower score means that a gene is more likely to be dependent in a given cell line. A score of 0 is equivalent to a gene that is not essential whereas a score of -1 corresponds to the median of all common essential genes.
Common Essential: A gene which, in a large, pan-cancer screen, ranks in the top X most depleting genes in at least 90% of cell lines. X is chosen empirically using the minimum of the distribution of gene ranks in their 90th percentile least depleting lines.


Enriched Lineages

CRISPR

Dependency Score (CERES)

1. Melanoma (1.1e-17) n=45
2. Skin (4.6e-15) n=52
3. Lymphocyte (9.3e-05) n=19
4. Upper Aerodigestive (2.0e-04) n=29
5. Upper Aerodigestive Squamous (2.0e-04) n=29
6. Multiple Myeloma (2.2e-04) n=20
7. Plasma Cell (2.2e-04) n=20

RNAi

Dependency Score (DEMETER2)

1. Neuroblastoma (2.4e-06) n=9
2. Peripheral Nervous System (2.4e-06) n=9

Enriched lineages have p-values < 0.0005 (shown in parentheses). n= indicates the number of cell lines plotted in that lineage.


Expression & CN

Expression


Copy Number log2(relative to ploidy + 1)

Expression: RNASeq files are aligned with STAR and quantified with RSEM, then TPM-normalized. Reported values are log2(TPM+1).

Copy number: The relative copy number pipeline used varies by cell line. For around 1000 lines, Sanger WES data was used, while for around 700 lines, Broad WES data was used. The remaining lines use SNP array data as explained in 10.1038/s41586-019-1186-3. See 10.1101/720243 for details on how CN source is chosen per line. Lines with WES data were processed through GATK using PONs from TCGA without matched normals and transformed by log2(x+1).



Top Co-dependencies

CRISPR (Avana) Public 19Q4

GenePearson correlation
PlotPTPN110.80
PlotSOS10.47
PlotEXTL30.40
PlotEGFR0.38
PlotGAB10.37

Combined RNAi (Broad, Novartis, Marcotte)

GenePearson correlation
PlotPTPN110.46
PlotSOS10.35
PlotC10orf1200.33
PlotCCDC1140.32
PlotRPN20.31

Target Tractability



Mutations

% of Cell lines



Description

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Mutation Public 19Q4

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Fusion 19Q4

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Methylation (1kb upstream TSS) (17 73401789-73402789)

CpG Methylation

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  • Official symbol: GRB2
  • Full name: growth factor receptor bound protein 2
  • Location:
  • Also known as: NCKAP2
  • Entrez ID: 2885
  • Ensembl ID: ENSG00000177885

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