Open Source Malaria
This is a contribution to the OpenSourceMalaria/Series4_PredictiveModel#1 event
Ben Irwin works at Optibrium Ltd. Mario Öeren works at Optibrium Ltd. Tom Whitehead works at Intellegens Ltd.
We will attempt to fill in the data matrix using some deep learning methods and provide this to the community.
We may attempt to use the method as described in this publication: Imputation of Assay Bioactivity Data Using Deep Learning T. M. Whitehead, B. W. J. Irwin, P. Hunt, M. D. Segall, and G. J. Conduit Journal of Chemical Information and Modeling 2019 59 (3), 1197-1204 DOI: 10.1021/acs.jcim.8b00768 https://pubs.acs.org/doi/10.1021/acs.jcim.8b00768
Other deep and not deep multiple imputation methods and QSAR methodsto be considered.
Not due to confusions with the submission format we will try for a simpler mutli assay method first. 01/10/2019: We will now attempt a QSAR vs. Quantum mechanical descriptor approach. We have taken the help of Mario Öeren on board who is an expert in drug metabolism and will help us with potential QM descriptors. This may include pka related endpoints.
Deadline appears to be 11th October.
Have noted the Master chemical list is there but there are inconsistencies.
I made changes to the Master chemicals list.
Working with project: OSMMaster_full EC50Chembl(uM),R^2,0.63
Ion Regulation Activity,R^2,0.59
Most Acidic pKa,R^2,0.39 (proxy column from QM model)
Most Basic pKa,R^2,0.78 (proxy column from QM model)
PfaI EC50 (Inh),R^2,0.70
Pfal (3D7) IC50 (Broad),R^2,0.95
Pfal (Dd2) IC50 (Broad),R^2,0.94
Pfal (K1) IC50 (Avery),R^2,0.96
Pfal (K1) IC50 (Guy),R^2,0.79
Pfal IC50 (Avery),R^2,0.87
Pfal IC50 (Dundee),R^2,0.66
Pfal IC50 (GSK),R^2,0.94
Pfal IC50 (Guy),R^2,0.83
Pfal IC50 (Ralph),R^2,0.79
Pfal IC50 (Syngene),R^2,0.83
Single Shot Inhibition %,R^2,0.93
Average R2 = 0.78675246513352
Some of the assays are to be trusted much more than others. Can't really comment on how well this model will work for the test compounds. It might depend on a few factors such as overlap of chemical space, whether my processing of the file was correct etc. Let's see what happens.