Skip to Main content Skip to Navigation
Journal articles

Prediction of PARP Inhibition with Proteochemometric Modelling and Conformal Prediction

Abstract : Poly(ADP-ribose) polymerases (PARPs) play a key role in DNA damage repair. PARP inhibitors act as chemo- and radio- sensitizers and thus potentiate the cytotoxicity of DNA damaging agents. Although PARP inhibitors are currently investigated as chemotherapeutic agents, their cross-reactivity with other members of the PARP family remains unclear. Here, we apply Proteochemometric Modelling (PCM) to model the activity of 181 compounds on 12 human PARPs. We demonstrate that PCM (R0 (2) test =0.65-0.69; RMSEtest =0.95-1.01 °C) displays higher performance on the test set (interpolation) than Family QSAR and Family QSAM (Tukey's HSD, α 0.05), and outperforms Inductive Transfer knowledge among targets (Tukey's HSD, α 0.05). We benchmark the predictive signal of 8 amino acid and 11 full-protein sequence descriptors, obtaining that all of them (except for SOCN) perform at the same level of statistical significance (Tukey's HSD, α 0.05). The extrapolation power of PCM to new compounds (RMSE=1.02±0.80 °C) and targets (RMSE=1.03±0.50 °C) is comparable to interpolation, although the extrapolation ability is not uniform across the chemical and the target space. For this reason, we also provide confidence intervals calculated with conformal prediction. In addition, we present the R package conformal, which permits the calculation of confidence intervals for regression and classification caret models.
Document type :
Journal articles
Complete list of metadatas

Cited literature [5 references]  Display  Hide  Download
Contributor : Marie Martin <>
Submitted on : Friday, November 18, 2016 - 10:52:42 AM
Last modification on : Monday, January 13, 2020 - 5:08:16 PM
Long-term archiving on: : Tuesday, March 21, 2017 - 1:00:18 AM


 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : jamais

Please log in to resquest access to the document




Isidro Cortés-Ciriano, Andreas Bender, Thérèse Malliavin. Prediction of PARP Inhibition with Proteochemometric Modelling and Conformal Prediction. Molecular Informatics, Wiley-VCH, 2015, 34 (6-7), pp.357 - 366. ⟨10.1002/minf.201400165⟩. ⟨pasteur-01399008⟩



Record views