Systematically studying kinase inhibitor induced signaling network signatures by integrating both therapeutic and side effects

PloS One
Hongwei ShaoXiaobo Zhou

Abstract

Substantial effort in recent years has been devoted to analyzing data based large-scale biological networks, which provide valuable insight into the topologies of complex biological networks but are rarely context specific and cannot be used to predict the responses of cell signaling proteins to specific ligands or compounds. In this work, we proposed a novel strategy to investigate kinase inhibitor induced pathway signatures by integrating multiplex data in Library of Integrated Network-based Cellular Signatures (LINCS), e.g. KINOMEscan data and cell proliferation/mitosis imaging data. Using this strategy, we first established a PC9 cell line specific pathway model to investigate the pathway signatures in PC9 cell line when perturbed by a small molecule kinase inhibitor GW843682. This specific pathway revealed the role of PI3K/AKT in modulating the cell proliferation process and the absence of two anti-proliferation links, which indicated a potential mechanism of abnormal expansion in PC9 cell number. Incorporating the pathway model for side effects on primary human hepatocytes, it was used to screen 27 kinase inhibitors in LINCS database and PF02341066, known as Crizotinib, was finally suggested with an optimal concentration ...Continue Reading

References

Jul 1, 1975·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·S A LattC D Scher
Dec 11, 1999·Nucleic Acids Research·M Kanehisa, S Goto
Jul 25, 2000·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·H Ellinger-ZiegelbauerE Nishida
Jun 7, 2002·Molecular Cell·Reinhart HeinrichTom A Rapoport
Jun 22, 2002·Journal of Theoretical Biology·Mineo MorohashiHiroaki Kitano
Mar 18, 2003·The Journal of Biological Chemistry·Sarah A WalterRonald J Hill
May 13, 2003·Nature Biotechnology·Alexei VazquezAlessandro Vespignani
Mar 17, 2004·Cancer Treatment Reviews·Juan Angel Fresno VaraManuel González-Barón
Oct 14, 2004·Bioinformatics·Peter J WoolfDouglas A Lauffenburger
Nov 30, 2004·Science·Insuk LeeEdward M Marcotte
Feb 16, 2005·Nature Biotechnology·Miles A FabianDavid J Lockhart
May 19, 2006·The New England Journal of Medicine·Marie E McDonnell, Lewis E Braverman
Jan 11, 2007·Biochemistry·Matthew P PatricelliJohn W Kozarich
Jul 14, 2007·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Jinliang XingXifeng Wu
Aug 7, 2007·Plant Physiology·Jane Geisler-LeeMatt Geisler
Oct 10, 2007·PLoS Computational Biology·Ryan N GutenkunstJames P Sethna
Oct 20, 2007·Expert Review of Anticancer Therapy·Manrique AlvarezLuis E Raez
Dec 7, 2007·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·James W JacobbergerDeena V Soni
Jan 26, 2008·Bioinformatics·Julio Saez-RodriguezPeter K Sorger
Feb 15, 2008·Proceedings of the National Academy of Sciences of the United States of America·Adrian Salic, Timothy J Mitchison
Dec 24, 2008·Nature Reviews. Cancer·Jianming ZhangNathanael S Gray
Jan 23, 2009·International Journal of Biological Sciences·Tina M Thornton, Mercedes Rincon
Jul 30, 2009·Molecular Systems Biology·Daniel C KirouacPeter W Zandstra
Dec 8, 2009·Bioinformatics·Bart S Hendriks, Christopher W Espelin
Nov 15, 2011·Nucleic Acids Research·Minoru KanehisaMao Tanabe

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Citations

Feb 13, 2016·Scientific Reports·Huiming PengXiaobo Zhou
Oct 4, 2017·Nucleic Acids Research·Shaoliang PengFei Li
Jul 8, 2016·Annals of Biomedical Engineering·Thomas E YankeelovGuy M Genin
Apr 24, 2016·American Journal of Physiology. Lung Cellular and Molecular Physiology·Jonathan M CiencewickiSteven R Kleeberger
Apr 8, 2017·BioMed Research International·Zhiwei JiXiaoliang Zhu
Feb 1, 2016·The Annals of Applied Statistics·William Chad YoungKa Yee Yeung

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Methods Mentioned

BETA
competition binding
competition
ELISA
Assay
PCR

Software Mentioned

ImageXpress
DataRail
KIEP ( Effect Prediction )
KINOMEscan
Matlab

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