Improved large-scale prediction of growth inhibition patterns using the NCI60 cancer cell line panel

Bioinformatics
Isidro Cortés-CirianoThérèse E Malliavin

Abstract

Recent large-scale omics initiatives have catalogued the somatic alterations of cancer cell line panels along with their pharmacological response to hundreds of compounds. In this study, we have explored these data to advance computational approaches that enable more effective and targeted use of current and future anticancer therapeutics. We modelled the 50% growth inhibition bioassay end-point (GI50) of 17,142 compounds screened against 59 cancer cell lines from the NCI60 panel (941,831 data-points, matrix 93.08% complete) by integrating the chemical and biological (cell line) information. We determine that the protein, gene transcript and miRNA abundance provide the highest predictive signal when modelling the GI50 endpoint, which significantly outperformed the DNA copy-number variation or exome sequencing data (Tukey's Honestly Significant Difference, P <0.05). We demonstrate that, within the limits of the data, our approach exhibits the ability to both interpolate and extrapolate compound bioactivities to new cell lines and tissues and, although to a lesser extent, to dissimilar compounds. Moreover, our approach outperforms previous models generated on the GDSC dataset. Finally, we determine that in the cases investigated ...Continue Reading

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Citations

Dec 2, 2015·Journal of Chemical Information and Modeling·Isidro Cortes-Ciriano, Andreas Bender
Jul 12, 2016·Journal of Chemical Information and Modeling·Isidro Cortes-Ciriano
Sep 25, 2017·F1000Research·Zhaleh SafikhaniBenjamin Haibe-Kains
Jan 18, 2020·Briefings in Bioinformatics·Delora BaptistaMiguel Rocha
Jul 23, 2016·Briefings in Bioinformatics·Francisco Azuaje
Sep 25, 2020·SAR and QSAR in Environmental Research·V V KleandrovaA Speck-Planche
Jan 13, 2021·Journal of Cheminformatics·Isidro Cortés-CirianoDaniel Svozil
Apr 4, 2021·Cancer Discovery·Bhavneet BhinderOlivier Elemento
Jul 3, 2021·Journal of Chemical Information and Modeling·Raghad Al-JarfDavid B Ascher
Oct 20, 2018·Journal of Chemical Information and Modeling·Isidro Cortés-Ciriano, Andreas Bender
Jun 27, 2019·Journal of Chemical Information and Modeling·Isidro Cortés-Ciriano, Andreas Bender
Oct 5, 2019·Journal of Chemical Information and Modeling·Alexey V ZakharovAnton Simeonov
Aug 21, 2018·Journal of Chemical Information and Modeling·Kathryn A GiblinAndreas Bender
Aug 22, 2018·Journal of Chemical Information and Modeling·Isidro Cortés-CirianoOliver Watson

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