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Timothy E H Allen

Timothy E H Allen
Ladder Therapeutics

PhD, MA, MSci

About

24
Publications
2,734
Reads
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309
Citations
Introduction
Toxicology is moving away from animal methods and towards in silico and in vitro alternatives. One such alternative is the adverse outcome pathway (AOP) framework for risk assessment, based on understanding the pathways behind toxicity. The molecular initiating event (MIE) is the key chemistry at the beginning of the pathway. MIEs are investigated using a combination of informatics and machine learning methods to answer the question; what is it about these chemicals that cause them to be toxic?
Additional affiliations
June 2016 - present
University of Cambridge
Position
  • PostDoc Position
Description
  • Mentoring graduate students at the Department of Chemistry in a pastoral role focussed on career development.
January 2016 - present
University of Cambridge
Position
  • PostDoc Position
Description
  • To computationally model molecules and receptors effectively we must construct 3D models. 3D quantitative structure activity relationships are being investigated to provide improved tools for the prediction of toxic effects of novel compounds.
October 2013 - present
University of Cambridge
Position
  • Undergraduate Supervisor
Description
  • Teaching of small groups of first year chemistry undergraduate students.
Education
October 2008 - June 2012
University of Cambridge
Field of study
  • Natural Sciences

Publications

Publications (24)
Article
Full-text available
Deep learning neural networks, constructed for the prediction of chemical binding at 79 pharmacologically important human biological targets, show extremely high performance on test data (accuracy 92.2 ± 4.2%, MCC 0.814 ± 0.093 and ROC-AUC 0.96 ± 0.04). A new molecular similarity measure, Neural Network Activation Similarity, has been developed, ba...
Article
Consumer and environmental safety decisions are based on exposure and hazard data, interpreted using risk assessment approaches. The adverse outcome pathway (AOP) conceptual framework has been presented as a logical sequence of events or processes within biological systems which can be used to understand adverse effects and refine current risk asse...
Article
The adverse outcome pathway (AOP) framework provides an alternative to traditional in vivo experiments for the risk assessment of chemicals. AOPs consist of a number of key events (KEs) linked by key event relationships (KERs) across a range of biological organization backed by scientific evidence. The first KE in the pathway is the molecular initi...
Article
Full-text available
The Ames mutagenicity assay is a long established in vitro test to measure the mutagenicity potential of a new chemical used in regulatory testing globally. One of the key computational approaches to modelling the Ames assay relies on the formation of chemical categories based on the different electrophilic compounds that are able to react directly...
Article
A molecular initiating event (MIE) is the gateway to an adverse outcome pathway (AOP), a sequence of events ending in an adverse effect. In silico predictions of MIEs are a vital tool in a modern, mechanism-focused approach to chemical risk assessment. For 90 biological targets representing important human MIEs, structural alert-based models have b...
Article
In silico (computational) methods continue to evolve as part of a robust 21st century public health strategy in risk assessment, relevant to all sectors of chemical safety including preclinical drug discovery, industrial chemicals testing, food and cosmetics. Alongside in vitro methods as components of intelligent testing and pathway driven strateg...
Article
Next-generation risk assessment (NGRA) involves the combination of in vitro and in silico models for more human-relevant, ethical, and sustainable human chemical safety assessment. NGRA requires a quantitative mechanistic understanding of the effects of chemicals across human biology (be they molecular, cellular, organ-level or higher) coupled with...
Article
Full-text available
Background: Humans are exposed to tens of thousands of chemical substances that need to be assessed for their potential toxicity. Acute systemic toxicity testing serves as the basis for regulatory hazard classification, labeling, and risk management. However, it is cost- and time-prohibitive to evaluate all new and existing chemicals using traditi...
Article
In recent times, machine learning has become increasingly prominent in predictive toxicology as it has shifted from in vivo studies toward in silico studies. Currently, in vitro methods together with other computational methods such as quantitative structure-activity relationship modeling and absorption, distribution, metabolism, and excretion calc...
Article
Having a measure of confidence in computational predictions of biological activity from in silico tools is vital when making predictions for new chemicals, for example, in chemical risk assessment. Where predictions of biological activity are used as an indicator of a potential hazard, false-negative predictions are the most concerning prediction;...
Chapter
The role of computers in science has changed dramatically because of the increase in computational power, accessible platforms for data storage and use, and the development of artificial intelligence and machine learning. This chapter addresses a number of important questions regarding the role of computers in science and presents some relevant exa...
Chapter
A key question in machine learning is how learning is accomplished. Humans learn through experience in our lives, and it would be extremely beneficial to have machines that can do the same thing. Therefore, we should try to develop them, especially as machines are far better at some tasks than humans, such as large-scale mathematical calculations a...
Article
Molecular initiating events (MIEs) are key events in adverse outcome pathways (AOPs) that link molecular chemistry to target biology. As they are based in chemistry, these interactions are excellent targets for computational chemistry approaches to in silico modelling. In this work, we aim to link ligand chemical structure to MIEs for androgen rece...
Article
Full-text available
In the last decade, adverse outcome pathways have been introduced in the fields of toxicology and risk assessment of chemicals as pragmatic tools with broad application potential. While their use in the pharmaceutical and cosmetics sectors has been well documented, their application in the food area remains largely unexplored. In this respect, an e...
Article
There is a growing recognition that application of mechanistic approaches to understand cross-species shared molecular targets and pathway conservation in the context of hazard characterization, provide significant opportunities in risk assessment (RA) for both human health and environmental safety. Specifically, it has been recognized that a more...
Article
The aim of human toxicity risk assessment is to determine a safe dose or exposure to a chemical for humans. This requires an understanding of the exposure of a person to a chemical, and how much of the chemical is required to cause an adverse effect. To do this computationally we need to understand how much of a chemical is required to perturb norm...
Article
Full-text available
There is considerable interest in adverse outcome pathways (AOPs) as a means of organizing biological and toxicological information to assist in data interpretation and method development. While several chemical sectors have shown considerable progress in applying this approach, this has not been the case in the food sector. In the present study, s...
Article
Molecular Initiating Events (MIEs) are important concepts for in silico predictions. They can be used to link chemical characteristics to biological activity through an adverse outcome pathway (AOP). In this work, we capture chemical characteristics in 2D structural alerts, which are then used as models to predict MIEs. An automated procedure has b...
Article
Molecular initiating events (MIEs) can be boiled down to chemical interactions. Chemicals that interact must have intrinsic properties that allow them to do this, be these stereochemical, electronic or otherwise. In an attempt to discover some of these chemical characteristics we have utilized chemical informatics approaches, searching the ChEMBL d...

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