A machine learning approach to define antimalarial drug action from heterogeneous cell-based screens

Drug resistance threatens the effective prevention and treatment of an ever-increasing range of human infections. This highlights an urgent need for new and improved drugs with novel mechanisms of action to avoid cross-resistance. Current cell-based drug screens are, however, restricted to binary live/dead readouts with no provision for mechanism of action prediction. Machine learning methods are increasingly being used to improve information extraction from imaging data. These methods, however, work poorly with heterogeneous cellular phenotypes and generally require time-consuming human-led training. We have developed a semi-supervised machine learning approach, combining human- and machine-labeled training data from mixed human malaria parasite cultures. Designed for high-throughput and high-resolution screening, our semi-supervised approach is robust to natural parasite morphological heterogeneity and correctly orders parasite developmental stages. Our approach also reproducibly detects and clusters drug-induced morphological outliers by mechanism of action, demonstrating the potential power of machine learning for accelerating cell-based drug discovery.

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A machine learning approach to define antimalarial drug action from heterogeneous cell-based screens

10.1101/2019.12.19.882480 ◽

2019 ◽

Cited By ~ 1

Author(s):

George W. Ashdown ◽

Michelle Dimon ◽

Minjie Fan ◽

Fernando Sánchez-Román Terán ◽

Katrin Witmer ◽

...

Keyword(s):

Machine Learning ◽

Mechanism Of Action ◽

Malaria Parasite ◽

Training Data ◽

Supervised Machine Learning ◽

Cross Resistance ◽

Learning Approach ◽

Imaging Data ◽

Effective Prevention ◽

Machine Learning Approach

AbstractDrug resistance threatens the effective prevention and treatment of an ever-increasing range of human infections. This highlights an urgent need for new and improved drugs with novel mechanisms of action to avoid cross-resistance. Current cell-based drug screens are, however, restricted to binary live/dead readouts with no provision for mechanism of action prediction. Machine learning methods are increasingly being used to improve information extraction from imaging data. Such methods, however, work poorly with heterogeneous cellular phenotypes and generally require time-consuming human-led training. We have developed a semi-supervised machine learning approach, combining human- and machine-labelled training data from mixed human malaria parasite cultures. Designed for high-throughput and high-resolution screening, our semi-supervised approach is robust to natural parasite morphological heterogeneity and correctly orders parasite developmental stages. Our approach also reproducibly detects and clusters drug-induced morphological outliers by mechanism of action, demonstrating the potential power of machine learning for accelerating cell-based drug discovery.One Sentence SummaryA machine learning approach to classifying normal and aberrant cell morphology from plate-based imaging of mixed malaria parasite cultures, facilitating clustering of drugs by mechanism of action.

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HAMLET

Terminology ◽

10.1075/term.20017.rig ◽

2021 ◽

Author(s):

Ayla Rigouts Terryn ◽

Véronique Hoste ◽

Els Lefever

Keyword(s):

Machine Learning ◽

Language Processing ◽

Hybrid Approach ◽

Substantial Effect ◽

Training Data ◽

Supervised Machine Learning ◽

Learning Approach ◽

Term Extraction ◽

Machine Learning Approach ◽

Different Types

Abstract Automatic term extraction (ATE) is an important task within natural language processing, both separately, and as a preprocessing step for other tasks. In recent years, research has moved far beyond the traditional hybrid approach where candidate terms are extracted based on part-of-speech patterns and filtered and sorted with statistical termhood and unithood measures. While there has been an explosion of different types of features and algorithms, including machine learning methodologies, some of the fundamental problems remain unsolved, such as the ambiguous nature of the concept “term”. This has been a hurdle in the creation of data for ATE, meaning that datasets for both training and testing are scarce, and system evaluations are often limited and rarely cover multiple languages and domains. The ACTER Annotated Corpora for Term Extraction Research contain manual term annotations in four domains and three languages and have been used to investigate a supervised machine learning approach for ATE, using a binary random forest classifier with multiple types of features. The resulting system (HAMLET Hybrid Adaptable Machine Learning approach to Extract Terminology) provides detailed insights into its strengths and weaknesses. It highlights a certain unpredictability as an important drawback of machine learning methodologies, but also shows how the system appears to have learnt a robust definition of terms, producing results that are state-of-the-art, and contain few errors that are not (part of) terms in any way. Both the amount and the relevance of the training data have a substantial effect on results, and by varying the training data, it appears to be possible to adapt the system to various desired outputs, e.g., different types of terms. While certain issues remain difficult – such as the extraction of rare terms and multiword terms – this study shows how supervised machine learning is a promising methodology for ATE.

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Mol2vec: Unsupervised Machine Learning Approach with Chemical Intuition

10.26434/chemrxiv.5513581.v1 ◽

2017 ◽

Author(s):

Sabrina Jaeger ◽

Simone Fulle ◽

Samo Turk

Keyword(s):

Machine Learning ◽

Language Processing ◽

Supervised Machine Learning ◽

Learning Approach ◽

Learning Approaches ◽

Unsupervised Machine Learning ◽

Feature Representations ◽

Machine Learning Approach ◽

The Individual ◽

Vector Representations

Inspired by natural language processing techniques we here introduce Mol2vec which is an unsupervised machine learning approach to learn vector representations of molecular substructures. Similarly, to the Word2vec models where vectors of closely related words are in close proximity in the vector space, Mol2vec learns vector representations of molecular substructures that are pointing in similar directions for chemically related substructures. Compounds can finally be encoded as vectors by summing up vectors of the individual substructures and, for instance, feed into supervised machine learning approaches to predict compound properties. The underlying substructure vector embeddings are obtained by training an unsupervised machine learning approach on a so-called corpus of compounds that consists of all available chemical matter. The resulting Mol2vec model is pre-trained once, yields dense vector representations and overcomes drawbacks of common compound feature representations such as sparseness and bit collisions. The prediction capabilities are demonstrated on several compound property and bioactivity data sets and compared with results obtained for Morgan fingerprints as reference compound representation. Mol2vec can be easily combined with ProtVec, which employs the same Word2vec concept on protein sequences, resulting in a proteochemometric approach that is alignment independent and can be thus also easily used for proteins with low sequence similarities.

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