Cancer Genetic Interaction database 2.0

What is CGIdb2.0?

CGIdb2.0, an updated database, offers a repository of comprehensively published genetic interactions (GIs) gene pairs, includes synthetic lethality (SL), synthetic viability (SV). CGIdb2.0 serves as a timely and valuable resource for further investigation of the roles of GIs in cancer mechanisms and drug effects.

What data types are included in the CGIdb2.0?

CGIdb2.0 catalogs SL and SV gene pairs across more than twenty cancer types. Additionally, CGIdb2.0 collects quantitative chemical-genetic interaction pairs and enhances the interpretation of GIs mechanisms using within-protein complex or pathway model and between-protein complex or pathway model. CGIdb2.0 also tests correlation of GIs gene pairs that influenced the drug effect based on multi-omics data sourced from TCGA.

How do I cite the CGIdb2.0?

Kindly acknowledge the following portal papers in your citation:

Title: “Harnessing genetic interactions for prediction of immune checkpoint inhibitors response signatures in cancer cells.”

Additionally, please ensure to attribute the source of the data, especially if derived from publicly available datasets.

What are the features of the CGIdb 2.0?

The key features of CGIdb 2.0 are conveniently listed in the left-hand menu. Navigate through various options by clicking on them to access specific pages of interest.

HOME

The homepage offers a concise introduction to CGIdb 2.0, featuring a user-friendly 'Statistical Humanoid Chart' for easy visualization.

Additionally, you can find links to external public databases utilized in CGIdb 2.0 conveniently located at the bottom of the page.

SEARCH

The search page provides a user-friendly interface for searching and browsing GI information for genes of interest.

DOWNLOAD

The DOWNLOAD page is categorized into four sections: Tissue, Source, Drug and Complex/Pathway.

Each category provides the number of genetic interactions related to specific tissues, sources, drugs, and complex/pathway information.

FAQ

The FAQ page serves as your comprehensive guide to navigating and utilizing CGIdb 2.0.

CONTACT US

You can reach out to us by sending an email to guyunyan@ems.hrbmu.edu.cn.

How do I use CGIdb2.0 to get the information I want?

On the Search page, you can initiate your search behaviour (A). CGIdb2.0 enables you to search for SL/SV interactions by gene Entrez ID and gene symbol (B). Additionally, you can explore genetic interactions information based on GI types, immune checkpoint genes or tissue types (C).

What are the features of the searching result interface?

The result interface is divided into two main areas:

  • Function panel (A)
  • Display platform (B)

You can navigate and utilize the features efficiently using the function panel (A) and explore detailed information through the display platform (B).

The function panel provides following function buttons.

What is the button for?

Press to link the result function panel. The basic information of the gene you are searching for will be listed in the following table.

What is the button for?

Press to access the result function panel. The SL/SV interaction network is displayed on the right, and you can hide it by pressing again.

You can choose the cancer type of interest from the node list, and the information is displayed as follows:

The top panel (A) illustrates the distribution of gene alterations in samples from the TCGA cohorts. The colors represent different alteration types: green for mutation, red for amplification, and blue for deletion.

The bottom panel (B) displays the result of statistical tests for co-alteration, co-expression, and co-methylation between two genes for SL or SV interactions.

What is the button for?

Press to link to the function panel, where you can access detailed information for each pair of genetic interactions. This includes gene symbols, tissue types, confidence scores, source, and drug effects. The 'Confidence Score' reflects the reliability of the genetic interaction, and 'Source' indicates the origin of the genetic interaction.

Press to access the drug response test boxplot.

What is the button for?

Press to link the result to the function panel. The table below displays the interactions between the gene you are searching for and chemical compounds, with the 'score' indicating the strength of the interaction effect.

What is the button for?

Press in the result function panel. The interactions between the gene you are searching for and others will be listed in the table below. The table also indicates the type of relationship ('within' or 'between') between the two complexes to which the gene pair belongs.

What is the button for?

Press in the result function panel. The interactions between the gene you are searching for and others will be listed in the table below. The table also indicates the relationship type ('within' or 'between') between the two pathways to which the gene pair belongs.

What is the button for?

Press and the network will pop up. You can add your own nodes to the original network diagram, name them, and select the interaction types ('SL', 'SV', or 'No Types').

What is the button for?

Press and you can left-click and drag from one node to another to add an edge between them.

What is the button for?

Press and you can save the network on the bottom canvas as .PNG file.

What is the button for?

Press and you will see the word cloud, where the size of the gene symbol corresponds to the frequency of the gene.

How should I interpret the score?

The SV and SL interactions in CGIdb2.0 were obtained from different types of sources, including biochemical assays, text mining results. In addition, biochemical assays were based on different experimental technologies and platforms, such as shRNA, CRISPR and drug inhibition. Because multiple types of evidence are conducive to the identification of SV (SL) interactions, an integrative confidence score combining scores from these evidence sources can provide an overall estimation of the reliability of SV (SL) interaction. In principle, we supposed that (i) the contribution of experimental evidence to the confidence score is more significant than the text mining and that (ii) the SV (SL) interactions supported by more evidence sources should be beneficial to the confidence score. The scoring procedures were divided into two steps, i.e., quantification and integration. A large number of SV (SL) interactions collected from other studies had only qualitative annotation evidence (such as “high-throughput” or “low-throughput”), or technological descriptions of wet-lab experiments (such as “CRISPR screening” or “shRNA screening”). Thus, it was necessary to assign quantitative scores to the SV (SL) interactions before the calculation of integrative scores. Similar to the scoring scheme from SLDB (http://histone.sce.ntu.edu.sg/SynLethDB/), the quantitative scores were assigned based on the experimental methods as shown in the following Table 1. For instance, “Mutant & Mutant” indicated that two genes in SV (SL) interactions were disturbed by transgenic or genetic deletions. Moreover, “RNA interference & Mutant” indicated that one gene was perturbed by RNAi and that the other was perturbed via mutation. In summary, the SV (SL) interactions obtained from low-throughput experiments were considered to be more reliable than the results from high-throughput experiments due to the lower false positive rate. And, a higher confidence score was assigned to low-throughput evidence than high-throughput evidence. Compared to other RNA interference experiments (such as shRNA, siRNA and dsRNA), the CRISPR/Cas9 screen had lower off-target effects, which were assigned higher confidence scores similar to mutation and transfection experiments.

The formula to combine the individual scores as follows:

where S represents the integrative score corresponding to the experimental evidence; Pi is the individual score; and n is the total number of experimental supporting evidence

Method Score
Mutant & Mutant 0.9
CRISPR 0.9
Low-throughput 0.8
RNA interference & Mutant 0.75
Bi-specifie RNA interference 0.5
RNA interference & Drug inhibition 0.5
High-throughput 0.5

How do I interpret the DOWNLOAD page?

At the top of the page is a summary of the data cohort.

The details of the cohort is showed by table (left) and pie chart (right).

And you can press to download all datasets which CGIdb 2.0 contains (A).

Which studies are included in CGIdb 2.0?

Study and Reference Journal Total Number Method
SynLethDB 2.0: a web-based knowledge graph database on synthetic lethality for novel anticancer drug discovery. DATABASE 36850 DAISY/DECIPHER/Text Mining/RNAi/Synlethality
Genetic Interaction-Based Biomarkers Identification for Drug Resistance and Sensitivity in Cancer Cells. Mol Ther Nucleic Acids 13899 Mutation exclusivity
Toward an integrated map of genetic interactions in cancer cells. Mol Syst Biol 13176 CRISPR
A Network of Conserved Synthetic Lethal Interactions for Exploration of Precision Cancer Therapy. Mol Cell 5476 Network
Predicting cancer-specific vulnerability via data-driven detection of synthetic lethality. Cell 2714 DAISY
Synthetic Lethality-based Identification of Targets for Anticancer Drugs in the Human Signaling Network. Sci Rep 2555 Network
Synthetic viability induces resistance to immune checkpoint inhibitors in cancer cells. Br J Cancer 1861 CRISPR
Synthetic sickness or lethality points at candidate combination therapy targets in glioblastoma. Int J Cancer 1776 somatic alteration and expression
Connectivity Homology Enables Inter-Species Network Models of Synthetic Lethality. PLoS Comput Biol 1487 connectivity-homology-based models
Identifying Lethal Dependencies with HUGE Predictive Power. Cancers (Basel) 1299 CRISPR-Cas9/RNAi
Genome-wide prediction of synthetic rescue mediators of resistance to targeted and immunotherapy. Mol Syst Biol 971 CRISPR/Expression
Multi-omic measurement of mutually exclusive loss-of-function enriches for candidate synthetic lethal gene pairs. BMC Genomics 944 Mutation exclusivity
Inferring synthetic lethal interactions from mutual exclusivity of genetic events in cancer. Biol Direct 815 Mutation exclusivity
Widespread genetic epistasis among cancer genes. Nat Commun 793 RNAi
Humanized yeast genetic interaction mapping predicts synthetic lethal interactions of FBXW7 in breast cancer. BMC Med Genomics 772 Expression
Therapeutic relevance of the protein phosphatase 2A in cancer. Oncotarget 464 DAISY
Mapping genetic interactions in human cancer cells with rnAi and multiparametric phenotyping. Nat Methods 419 RNAi
Pan-Cancer Analysis of Potential Synthetic Lethal Drug Targets Specific to Alterations in DNA Damage Response. Front Oncol 374 Mutual exclusivity and somatic mutations
Genetic interaction mapping in mammalian cells using CRISPR interference. Nat Methods 311 CRISPR
Predicting human genetic interactions from cancer genome evolution. PLoS One 270 Expression
Discovery of synthetic lethal and tumor suppressor paralog pairs in the human genome. Cell Rep 268 CRISPR
GEMINI: a variational Bayesian approach to identify genetic interactions from combinatorial CRISPR screens. Genome Biol 233 CRISPR
Integrative analysis of large-scale loss-of-function screens identifies robust cancer-associated genetic interactions. Elife 229 CRISPR
A negative genetic interaction map in isogenic cancer cell lines reveals cancer cell vulnerabilities. Mol Syst Biol 204 RNAi
Combinatorial CRISPR-Cas9 screens for de novo mapping of genetic interactions. Nat Methods 191 CRISPR
Decoding directional genetic dependencies through orthogonal CRISPR/Cas screens. biorxiv 134 CRISPR
Comprehensive prediction of robust synthetic lethality between paralog pairs in cancer cell lines. Cell Syst 126 CRISPR
Combinatorial CRISPR screen identifies fitness effects of gene paralogues. Nat Commun 104 CRISPR
Ranking novel cancer driving synthetic lethal gene pairs using TCGA data. Oncotarget 101 Mutation exclusivity
Identification of potential synthetic lethal genes to p53 using a computational biology approach. BMC Med Genomics 96 Expression
Identification of synthetic lethal pairs in biological systems through network information centrality. Mol Biosyst 89 Network
Determination of synthetic lethal interactions in KRAS oncogene-dependent cancer cells reveals novel therapeutic targeting strategies. Cell Res 80 RNAi
Cancer type-dependent genetic interactions between cancer driver alterations indicate plasticity of epistasis across cell types. Mol Syst Biol 52 permut
Synergistic drug combinations for cancer identified in a CRISPR screen for pairwise genetic interactions. Nat Biotechnol 38 CRISPR
Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1. Nature 33 RNAi

Detailed information on datasets involving samples treated with immune checkpoint inhibitors.

Datasets Number of samples Cancer ICI type
Lozano2022 53 Melanoma anti-PD1/anti-PD1+CTLA4 inhibitor
YeonKim2020 27 NSCLC anti-PD-1/anti-PD-L1inhibitor
Lee2021 22 NSCLC immune checkpoint inhibitor
Gide2019 91 Melanoma anti-PD1/anti-PDL1+anti-CTLA4 inhibitor
Liu2019 121 Melanoma anti-PD1 inhibitor
Riaz2017 62 Melanoma anti-PD1 inhibitor
Lauss2017 25 Melanoma anti-IL-2/anti-CTLA4 inhibitor
VanAllen2015 40 Melanoma anti-CTLA4 inhibitor
Snyder2014 21 Melanoma anti-CTLA4 inhibitor