A Middle-Out Modeling Strategy to Extend a Colon Cancer Logical Model Improves Drug Synergy Predictions in Epithelial-Derived Cancer Cell Lines

Frontiers in Molecular Biosciences
Eirini TsirvouliMartin Kuiper

Abstract

Cancer is a heterogeneous and complex disease and one of the leading causes of death worldwide. The high tumor heterogeneity between individuals affected by the same cancer type is accompanied by distinct molecular and phenotypic tumor profiles and variation in drug treatment response. In silico modeling of cancer as an aberrantly regulated system of interacting signaling molecules provides a basis to enhance our biological understanding of disease progression, and it offers the means to use computer simulations to test and optimize drug therapy designs on particular cancer types and subtypes. This sets the stage for precision medicine: the design of treatments tailored to individuals or groups of patients based on their tumor-specific molecular cancer profiles. Here, we show how a relatively large manually curated logical model can be efficiently enhanced further by including components highlighted by a multi-omics data analysis of data from Consensus Molecular Subtypes covering colorectal cancer. The model expansion was performed in a pathway-centric manner, following a partitioning of the model into functional subsystems, named modules. The resulting approach constitutes a middle-out modeling strategy enabling a data-driven ...Continue Reading

References

Dec 1, 1973·Journal of Theoretical Biology·R Thomas
Apr 1, 1973·Journal of Theoretical Biology·L Glass, S A Kauffman
Dec 11, 1999·Nucleic Acids Research·M Kanehisa, S Goto
Jul 15, 2000·Neuron·P SmolenJ H Byrne
Sep 28, 2004·Nature Genetics·Eran SegalAviv Regev
Dec 2, 2004·Proceedings of the National Academy of Sciences of the United States of America·Stuart KauffmanCarl Troein
May 21, 2005·Physical Review Letters·Sui HuangDonald E Ingber
Apr 28, 2006·Nature Genetics·Michael ReichJill P Mesirov
May 12, 2009·Bio Systems·A NaldiC Chaouiya
Oct 30, 2010·Nature Reviews. Drug Discovery·Shivanni KummarJames H Doroshow
Mar 1, 2011·Physics of Life Reviews·Dirk M LorenzMichael W Deem
Dec 7, 2011·Journal of Internal Medicine·J BachmannU Klingmüller
Mar 30, 2012·Omics : a Journal of Integrative Biology·Guangchuang YuQing-Yu He
Jul 12, 2012·Nature Biotechnology·Bissan Al-LazikaniPaul Workman
Jul 20, 2012·Nature·UNKNOWN Cancer Genome Atlas Network
Aug 9, 2012·BMC Systems Biology·Tomáš HelikarJim A Rogers
Sep 27, 2012·Physical Biology·Rui-Sheng WangRéka Albert
May 2, 2013·Cancer Medicine·Evangelia KoutsogiannouliNikolaos A Papanikolaou
Jun 12, 2013·Molecular Systems Biology·Bertram KlingerNils Blüthgen
Nov 20, 2013·PLoS Computational Biology·Luca GriecoDenis Thieffry
Feb 28, 2014·World Journal of Gastroenterology : WJG·Fabio CoppedèLucia Migliore
Apr 8, 2014·Biochimica Et Biophysica Acta·Gabriel BretonesJavier León
Jun 27, 2014·BMC Bioinformatics·Alan Veliz-CubaReinhard Laubenbacher
Sep 4, 2014·Microbiology and Molecular Biology Reviews : MMBR·Joana C XavierIsabel Rocha
Nov 13, 2014·Nature Communications·Jianxi GaoAlbert-László Barabási
Jul 15, 2015·Folia Histochemica Et Cytobiologica·Piotr M Wierzbicki, Agnieszka Rybarczyk
Aug 13, 2015·International Journal of Cancer. Journal International Du Cancer·Kaitlyn E VinsonGeorge Sigounas
Sep 1, 2015·PLoS Computational Biology·Åsmund FlobakAstrid Lægreid
Jan 1, 2014·IEEE/ACM Transactions on Computational Biology and Bioinformatics·Sriganesh SrihariMark A Ragan
Oct 13, 2015·Nature Medicine·Justin GuinneySabine Tejpar
Oct 16, 2015·Nucleic Acids Research·Livia PerfettoGianni Cesareni
Oct 17, 2015·Annual Review of Medicine·Ingrid A Mayer, Carlos L Arteaga

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Methods Mentioned

BETA
RNA-Seq

Key Resources (RRID) Mentioned

CVCL_0139
CVCL_0218
CVCL_0105
CVCL_0547
CVCL_0419
CVCL_1056
CVCL_1690
CVCL_1780

Software Mentioned

clusterProfiler
Paradigm
ACSNmineR
CASCADE
Signor
GISTIC
edgeR RNA - Seq expression analysis package
GenePattern
MutSigCV
BNReduction

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