Reverse Engineering Cancer: Inferring Transcriptional Gene Signatures from Copy Number Aberrations with ICAro

Cancers
Davide AngeliMatteo Pallocca

Abstract

The characterization of a gene product function is a process that involves multiple laboratory techniques in order to silence the gene itself and to understand the resulting cellular phenotype via several omics profiling. When it comes to tumor cells, usually the translation process from in vitro characterization results to human validation is a difficult journey. Here, we present a simple algorithm to extract mRNA signatures from cancer datasets, where a particular gene has been deleted at the genomic level, ICAro. The process is implemented as a two-step workflow. The first one employs several filters in order to select the two patient subsets: the inactivated one, where the target gene is deleted, and the control one, where large genomic rearrangements should be absent. The second step performs a signature extraction via a Differential Expression analysis and a complementary Random Forest approach to provide an additional gene ranking in terms of information loss. We benchmarked the system robustness on a panel of genes frequently deleted in cancers, where we validated the downregulation of target genes and found a correlation with signatures extracted with the L1000 tool, outperforming random sampling for two out of six L10...Continue Reading

References

Sep 28, 2013·Nature Genetics·Travis I ZackRameen Beroukhim
Jan 22, 2015·Nucleic Acids Research·Matthew E RitchieGordon K Smyth
May 23, 2015·Molecular Cell·Michael Boettcher, Michael T McManus
Jul 3, 2015·Science Translational Medicine·Leonard P Freedman
Mar 2, 2016·International Journal of Molecular Sciences·Unnikrishnan UnniyampurathManoj N Krishnan
May 5, 2016·Nucleic Acids Research·Maxim V KuleshovAvi Ma'ayan
May 10, 2016·Nature Biotechnology·David W MorgensMichael C Bassik
Mar 16, 2017·Development·Meritxell HuchAlfonso Martinez-Arias
Jul 6, 2017·Nature·Paul A Northcott
Aug 25, 2017·Nature·Gordon J LithgowPatrick Phillips
Dec 9, 2017·Database : the Journal of Biological Databases and Curation·Steve LefeverPieter Mestdagh

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Citations

Oct 28, 2019·Cancers·Chad Brenner

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Methods Mentioned

BETA
shRNA knockout
RNA-seq
ChIP-seq
Protein Arrays

Software Mentioned

ICAro ( gene signature Inference system from
Enrichr
Python
Enrichr API
R script limma
cBioPortal
GISTIC
limma
Firebrowse
randomForest

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