Mervin, LH;
Bulusu, KC;
Kalash, L;
Afzal, AM;
Svensson, F;
Firth, MA;
Barrett, I;
... Bender, A; + view all
(2018)
Orthologue chemical space and its influence on target prediction.
Bioinformatics
, 34
(1)
pp. 72-79.
10.1093/bioinformatics/btx525.
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Abstract
Motivation In silico approaches often fail to utilize bioactivity data available for orthologous targets due to insufficient evidence highlighting the benefit for such an approach. Deeper investigation into orthologue chemical space and its influence toward expanding compound and target coverage is necessary to improve the confidence in this practice. Results Here we present analysis of the orthologue chemical space in ChEMBL and PubChem and its impact on target prediction. We highlight the number of conflicting bioactivities between human and orthologues is low and annotations are overall compatible. Chemical space analysis shows orthologues are chemically dissimilar to human with high intra-group similarity, suggesting they could effectively extend the chemical space modelled. Based on these observations, we show the benefit of orthologue inclusion in terms of novel target coverage. We also benchmarked predictive models using a time-series split and also using bioactivities from Chemistry Connect and HTS data available at AstraZeneca, showing that orthologue bioactivity inclusion statistically improved performance.
| Type: | Article |
|---|---|
| Title: | Orthologue chemical space and its influence on target prediction |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/bioinformatics/btx525 |
| Publisher version: | https://doi.org/10.1093/bioinformatics/btx525 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10056785 |
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