Prediction of Compound Profiling Matrices Using Machine Learning

ACS Omega
Raquel Rodríguez-PérezJürgen Bajorath

Abstract

Screening of compound libraries against panels of targets yields profiling matrices. Such matrices typically contain structurally diverse screening compounds, large numbers of inactives, and small numbers of hits per assay. As such, they represent interesting and challenging test cases for computational screening and activity predictions. In this work, modeling of large compound profiling matrices was attempted that were extracted from publicly available screening data. Different machine learning methods including deep learning were compared and different prediction strategies explored. Prediction accuracy varied for assays with different numbers of active compounds, and alternative machine learning approaches often produced comparable results. Deep learning did not further increase the prediction accuracy of standard methods such as random forests or support vector machines. Target-based random forest models were prioritized and yielded successful predictions of active compounds for many assays.

References

Feb 16, 2005·Nature Biotechnology·Miles A FabianDavid J Lockhart
Sep 15, 2005·Neural Networks : the Official Journal of the International Neural Network Society·Liva RalaivolaPierre Baldi
Mar 28, 2006·Journal of Chemical Information and Modeling·Dumitru ErhanYoshua Bengio
Jan 6, 2007·Journal of Computer-aided Molecular Design·Beining ChenNikolaus Stiefl
Dec 11, 2008·IEEE Transactions on Systems, Man, and Cybernetics. Part B, Cybernetics : a Publication of the IEEE Systems, Man, and Cybernetics Society·Yuchun TangSven Krasser
May 13, 2009·Journal of Chemical Information and Modeling·Sebastian G Rohrer, Knut Baumann
Oct 6, 2009·Journal of Chemical Information and Modeling·Pekka TiikkainenOlli Kallioniemi
Oct 15, 2009·Bioinformatics·Qingliang LiStephen H Bryant
Apr 30, 2010·Journal of Chemical Information and Modeling·David Rogers, Mathew Hahn
Feb 22, 2011·Nature Chemical Biology·James T MetzPhilip J Hajduk
Jun 22, 2011·Expert Opinion on Drug Discovery·Xiang-Qun Xie
Nov 1, 2011·Nature Biotechnology·Theonie AnastassiadisJeffrey R Peterson
May 16, 2012·Journal of Chemical Information and Modeling·Alexandre Varnek, Igor Baskin
Jun 22, 2012·Journal of Medicinal Chemistry·Michael M MysingerBrian K Shoichet
Nov 12, 2013·Nucleic Acids Research·A Patrícia BentoJohn P Overington
Feb 15, 2014·Journal of Chemical Information and Modeling·Alexey V ZakharovMarc C Nicklaus
Jan 31, 2015·Journal of Chemical Information and Modeling·Junshui MaVladimir Svetnik
Oct 27, 2015·Nature Biotechnology·Jonathan M ElkinsWilliam J Zuercher
Jul 28, 2016·Expert Opinion on Drug Discovery·Sunghwan Kim
Oct 11, 2010·Molecular Informatics·Yusuf TanrikuluHans-Marcus Bitter
Aug 6, 2016·Molecular Informatics·Erik GawehnGisbert Schneider
Dec 3, 2016·Nucleic Acids Research·Yanli WangJian Zhang
Apr 6, 2017·Journal of Chemical Information and Modeling·Raquel Rodríguez-PérezJürgen Bajorath
May 5, 2017·ACS Central Science·Han Altae-TranVijay Pande
Jul 12, 2017·Journal of Chemical Information and Modeling·Bharath RamsundarVijay Pande
Nov 1, 2017·Journal of Cheminformatics·Eelke B LenselinkGerard J P van Westen
Dec 2, 2017·Science·Susan KlaegerBernhard Kuster
Jan 26, 2018·Drug Discovery Today·Hongming ChenThomas Blaschke
Jul 20, 2018·ACS Omega·Martin VogtJürgen Bajorath

❮ Previous
Next ❯

Citations

Jan 9, 2019·SLAS Discovery·Antje JanoschMarc Bickle
Oct 3, 2018·Future Science OA·Martin VogtJürgen Bajorath
Sep 8, 2019·International Journal of Molecular Sciences·Ovidiu Constantin BaltatuJosé Cipolla-Neto
Jan 5, 2021·Journal of Computer-aided Molecular Design·Akinori SatoKimito Funatsu
Feb 19, 2021·Journal of Computer-aided Molecular Design·Raquel Rodríguez-Pérez, Jürgen Bajorath
Apr 9, 2021·Scientific Reports·Ewerton Cristhian Lima de OliveiraClaudomiro de Souza de Sales Júnior
Jul 20, 2018·ACS Omega·Martin VogtJürgen Bajorath
Sep 13, 2019·Journal of Medicinal Chemistry·Raquel Rodríguez-Pérez, Jürgen Bajorath
Nov 13, 2018·Langmuir : the ACS Journal of Surfaces and Colloids·W Russ AlgarJérémie Asselin

❮ Previous
Next ❯

Methods Mentioned

BETA
feature extraction

Software Mentioned

scikit
ChEMBL
GraphConv
OEChem toolkit
learn
DeepChem
MoleculeNet
Molecular Operating Environment ( MOE )
VS
PubChem

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.