A MACHINE LEARNING APPROACH TO UNDERSTAND HOW INVERTEBRATES MAINTAIN HOMEOSTASIS UPON EXPOSURE TO PHARMACEUTICALS.
Lead Research Organisation:
Imperial College London
Department Name: School of Public Health
Abstract
The aim of this project will be to understand fundamental metabolomic and lipidomic homeostatic mechanisms in a freshwater invertebrate using machine learning to interrogate relationships.
Objectives:
1. To develop untargeted and targeted analytical (LC-MS/MS and GC-MS) methods for the determination of various classes of lipids (sphingolipids, phospholipids, triglycerides, fatty acids, etc.) from samples already collected and stored from BBSRC IPA project iNVERTOX (Ref: BB/P005187/1). A method for untargeted analysis will also be developed using full scan GC-MS and LC high resolution mass spectrometry (using hydrophilic interaction and reversed-phase liquid chromatography).
2. To establish a baseline lipid profile of the selected species (Gammarus pulex) and to use in silico classification tools such as principal component analysis and/or partial least squares analysis to identify confounding factors that influence the variability (e.g., sex, age, moult cycle and acclimatisation period).
3. Use convolutional neural networks for classification of LC- and GC-MS ion maps determined from Obj. 1 (lipidome) and iNVERTOX (metabolome) to enable classification and fundamental interpretation of cross-omic techniques.
4. Exposure of G. pulex to 5-10 selected pharmaceuticals at several concentrations to determine dose-response curves (internal concentrations) that disrupt homeostatic processes. Metabolomics and lipidomics will also be performed on these samples.
5. To develop and apply machine learning tools to the metabolomics and lipidomics data gathered in Obj. 4 to identify metabolic features across both datasets that are linked and correlated with dose-response curves and potential pathways. The metabolism of the probe pharmaceutical compounds will also be performed (via reversed-phase LC-HRMS)
Objectives:
1. To develop untargeted and targeted analytical (LC-MS/MS and GC-MS) methods for the determination of various classes of lipids (sphingolipids, phospholipids, triglycerides, fatty acids, etc.) from samples already collected and stored from BBSRC IPA project iNVERTOX (Ref: BB/P005187/1). A method for untargeted analysis will also be developed using full scan GC-MS and LC high resolution mass spectrometry (using hydrophilic interaction and reversed-phase liquid chromatography).
2. To establish a baseline lipid profile of the selected species (Gammarus pulex) and to use in silico classification tools such as principal component analysis and/or partial least squares analysis to identify confounding factors that influence the variability (e.g., sex, age, moult cycle and acclimatisation period).
3. Use convolutional neural networks for classification of LC- and GC-MS ion maps determined from Obj. 1 (lipidome) and iNVERTOX (metabolome) to enable classification and fundamental interpretation of cross-omic techniques.
4. Exposure of G. pulex to 5-10 selected pharmaceuticals at several concentrations to determine dose-response curves (internal concentrations) that disrupt homeostatic processes. Metabolomics and lipidomics will also be performed on these samples.
5. To develop and apply machine learning tools to the metabolomics and lipidomics data gathered in Obj. 4 to identify metabolic features across both datasets that are linked and correlated with dose-response curves and potential pathways. The metabolism of the probe pharmaceutical compounds will also be performed (via reversed-phase LC-HRMS)
People |
ORCID iD |
Leon Barron (Primary Supervisor) | |
Lucy Birkitt (Student) |
Studentship Projects
Project Reference | Relationship | Related To | Start | End | Student Name |
---|---|---|---|---|---|
BB/T508202/1 | 30/09/2019 | 30/07/2020 | |||
2268580 | Studentship | BB/T508202/1 | 30/09/2019 | 29/09/2023 | Lucy Birkitt |
Description | AstraZeneca |
Organisation | AstraZeneca |
Country | United Kingdom |
Sector | Private |
PI Contribution | I carry out research that is in the interest of AstraZeneca. They aim to promote ecopharmacovigilance and responsible industry practices for the disposal of pharmaceutical products. My project aims to determine the effect that pharmaceutical pollution has on the ecosystem at various levels, and therefore provide evidence for the argument of responsible practices by pharmaceutical producers. |
Collaborator Contribution | I receive funding by AstraZeneca, who top up not only my project money but also my stipend. I also have a supervisor from AstraZeneca who provides me with valuable advice and guidance on the research that I am carrying out. |
Impact | None yet. |
Start Year | 2019 |
Description | Journal Club - April 2022 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | I presented at our research group's journal club, speaking about my research into the effect of temperature on the pharmaceutical uptake of aquatic invertebrates. This sparked further questions on the topic. |
Year(s) Of Engagement Activity | 2022 |
Description | Journal Club - February 2023 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | I presented to my research group's journal club, presenting the results of a study investigating the effects of citalopram on the aquatic invertebrate G. pulex. It sparked further discussions and follow-up questions, as well as suggestions for further research. |
Year(s) Of Engagement Activity | 2023 |
Description | MRC Training Day Presentation |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | I presented my results on a study investigating temporal changes in water contamination over a 6 month period. It sparked further questions, including suggestions for future research. |
Year(s) Of Engagement Activity | 2022 |
Description | Poster presentation at SETAC 2020 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Industry/Business |
Results and Impact | A poster titled "Development and validation of a high-throughput method for biomonitoring exposure of invertebrates to contaminants in aquatic systems" was present at the SETAC Europe 30th Annual Meeting. Questions were asked by the audience, leading to further discussions. |
Year(s) Of Engagement Activity | 2020 |
URL | https://cdn.ymaws.com/www.setac.org/resource/resmgr/abstract_books/SETAC_SciCon_Abstract_book_v.pdf |
Description | Poster presentation at SETAC 2021 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Industry/Business |
Results and Impact | A poster titled "Quantitative determination of 80 contaminants of emerging concern in the freshwater amphipod, Gammarus pulex" was presented at the virtual SETAC Europe 31st Annual Meeting. It lead to questions being asked by the audience, which provoked interesting discussions and the potential for future collaborations. |
Year(s) Of Engagement Activity | 2021 |
URL | https://cdn.ymaws.com/www.setac.org/resource/resmgr/abstract_books/europe2021_abstract_book_.pdf |