FIREWORKS is an interactive web tool developed to facilitate interrogation of biological networks using unbiased genetic screens. Gene-gene relationships can be modeled by correlating essentiality scores across hundreds of cancer cell lines. This application allows you to visualize these relationships, build networks from them and leverage multi-omics data to investigate their underlying biology.
Network:
Any list of genes can be used as the
foundation of a network. These genes are referred to as
“source nodes”. The most coessential genes for each
source node form the “primary nodes".
The most coessential genes for each primary
node can be added by selecting “secondary nodes”.
Adding secondary nodes increases the compute
time, but often results in genes organizing into functional
modules. Frequently, these networks return nodes that are not
connected to any other sub-networks. This can result in a
cluttered looking visualization. To simplify these networks,
we have provided an option to remove isolated primary and
secondary nodes.
Coessentiality Heatmap:
In the “coessentiality heatmap” tab, you can investigate
the relative gene essentiality of a gene of interest and
its top coessential partners across cell lines. You must
specify the context, correlation direction and
rank cut-off for primary connections. Second order
connections are not included.
Multi-omics:
What determines which cell lines are dependent on a given
gene signature? The “multi-omics” tab aids in answering
this question, by integrating fitness data with other
functional characterizations of cancer cell lines.
Currently, you can use the “RNA” tool to perform
differential expression between the cell lines that are
the most and least dependent on a given gene, or
gene signature. The analysis depends on the provided context, p-value
cutoff and quantile cut-off.
IMPORTANT NOTE: Signatures
containing anti-correlated genes will still group cell
lines by dependence and perform differential expression between these
groups. This may not provide biologically
relevant results.
This tool is a work in progress. Please feel free to contact us with any questions, comments or other related inquiries. We will get back to you as soon as possible (david.amici@northwestern.edu).
FIREWORKS: a bottom-up approach to integrative coessentiality network analysis
David R Amici, Jasen M Jackson, Mihai I Truica, Roger S Smith, Byoung-Kyu Cho,
Sarki A Abdulkadir, Marc L Mendillo
Life Science Alliance 2020