Paired plasma lipidomics and proteomics analysis in the conversion from mild cognitive impairment to Alzheimer's disease
Background: Alzheimer's disease (AD) is a neurodegenerative condition for which there is currently no available medication that can stop its progression. Previous studies suggest that mild cognitive impairment (MCI) is a phase that precedes the disease. Therefore, a better understanding of the...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | artículo |
| Fecha de publicación: | 2024 |
| País: | España |
| Recursos: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:323202 |
| Acesso em linha: | https://ddd.uab.cat/record/323202 https://dx.doi.org/urn:doi:10.1016/j.compbiomed.2024.108588 |
| Access Level: | acceso abierto |
| Palavra-chave: | Alzheimer's disease Integrative omics Machine learning Metabolomics Mild cognitive impairment Proteomics |
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Paired plasma lipidomics and proteomics analysis in the conversion from mild cognitive impairment to Alzheimer's diseaseGómez-Pascual, A.|||0000-0003-2348-9083Xu, J.|||0000-0002-6341-5938Wretlind, A.|||0000-0001-6083-5227Shi, L.Buckley, Noel J.|||0000-0003-1152-0653Tijms, Betty M.|||0000-0002-2612-1797Vos, Stephanie J.B.|||0000-0002-2045-9818Engelborghs, Sebastiaan|||0000-0003-0304-9785Sleegers, Kristel|||0000-0002-0283-2332Wallin, Anders|||0000-0001-9506-0513Lleó, Alberto|||0000-0002-2568-5478Popp, Julius|||0000-0002-0068-0312Martinez-Lage, P.Streffer, J.Barkhof, Frederik|||0000-0003-3543-3706Zetterberg, Henrik|||0000-0003-3930-4354Visser, Pieter Jelle|||0000-0001-8008-9727Lovestone, Simon|||0000-0003-0473-4565Bertram, Lars|||0000-0002-0108-124XNevado-Holgado, Alejo|||0000-0001-9276-2720Proitsi, Petroula|||0000-0002-2553-6974Botía, Juan A.|||0000-0002-6992-598XLegido-Quigley, Cristina|||0000-0002-4018-214XNaccache, TalelHooshmand, KouroshGabrielli, MartinaLombardo, Marta Tiffanyten Kate, Mara|||0000-0002-8290-8543Frisoni, Giovanni B.|||0000-0002-6419-1753Gualerzi, AlicePicciolini, SilviaVerderio, ClaudiaAlzheimer's diseaseIntegrative omicsMachine learningMetabolomicsMild cognitive impairmentProteomicsBackground: Alzheimer's disease (AD) is a neurodegenerative condition for which there is currently no available medication that can stop its progression. Previous studies suggest that mild cognitive impairment (MCI) is a phase that precedes the disease. Therefore, a better understanding of the molecular mechanisms behind MCI conversion to AD is needed. Method: Here, we propose a machine learning-based approach to detect the key metabolites and proteins involved in MCI progression to AD using data from the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery Study. Proteins and metabolites were evaluated separately in multiclass models (controls, MCI and AD) and together in MCI conversion models (MCI stable vs converter). Only features selected as relevant by 3/4 algorithms proposed were kept for downstream analysis. Results: Multiclass models of metabolites highlighted nine features further validated in an independent cohort (0.726 mean balanced accuracy). Among these features, one metabolite, oleamide, was selected by all the algorithms. Further in-vitro experiments in rodents showed that disease-associated microglia excreted oleamide in vesicles. Multiclass models of proteins stood out with nine features, validated in an independent cohort (0.720 mean balanced accuracy). However, none of the proteins was selected by all the algorithms. Besides, to distinguish between MCI stable and converters, 14 key features were selected (0.872 AUC), including tTau, alpha-synuclein (SNCA), junctophilin-3 (JPH3), properdin (CFP) and peptidase inhibitor 15 (PI15) among others. Conclusions: This omics integration approach highlighted a set of molecules associated with MCI conversion important in neuronal and glia inflammation pathways.Universitat Autònoma de Barcelona. Departament de Medicina 22024-01-0120242024-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/323202https://dx.doi.org/urn:doi:10.1016/j.compbiomed.2024.108588reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:3232022026-06-06T12:50:31Z |
| dc.title.none.fl_str_mv |
Paired plasma lipidomics and proteomics analysis in the conversion from mild cognitive impairment to Alzheimer's disease |
| title |
Paired plasma lipidomics and proteomics analysis in the conversion from mild cognitive impairment to Alzheimer's disease |
| spellingShingle |
Paired plasma lipidomics and proteomics analysis in the conversion from mild cognitive impairment to Alzheimer's disease Gómez-Pascual, A.|||0000-0003-2348-9083 Alzheimer's disease Integrative omics Machine learning Metabolomics Mild cognitive impairment Proteomics |
| title_short |
Paired plasma lipidomics and proteomics analysis in the conversion from mild cognitive impairment to Alzheimer's disease |
| title_full |
Paired plasma lipidomics and proteomics analysis in the conversion from mild cognitive impairment to Alzheimer's disease |
| title_fullStr |
Paired plasma lipidomics and proteomics analysis in the conversion from mild cognitive impairment to Alzheimer's disease |
| title_full_unstemmed |
Paired plasma lipidomics and proteomics analysis in the conversion from mild cognitive impairment to Alzheimer's disease |
| title_sort |
Paired plasma lipidomics and proteomics analysis in the conversion from mild cognitive impairment to Alzheimer's disease |
| dc.creator.none.fl_str_mv |
Gómez-Pascual, A.|||0000-0003-2348-9083 Xu, J.|||0000-0002-6341-5938 Wretlind, A.|||0000-0001-6083-5227 Shi, L. Buckley, Noel J.|||0000-0003-1152-0653 Tijms, Betty M.|||0000-0002-2612-1797 Vos, Stephanie J.B.|||0000-0002-2045-9818 Engelborghs, Sebastiaan|||0000-0003-0304-9785 Sleegers, Kristel|||0000-0002-0283-2332 Wallin, Anders|||0000-0001-9506-0513 Lleó, Alberto|||0000-0002-2568-5478 Popp, Julius|||0000-0002-0068-0312 Martinez-Lage, P. Streffer, J. Barkhof, Frederik|||0000-0003-3543-3706 Zetterberg, Henrik|||0000-0003-3930-4354 Visser, Pieter Jelle|||0000-0001-8008-9727 Lovestone, Simon|||0000-0003-0473-4565 Bertram, Lars|||0000-0002-0108-124X Nevado-Holgado, Alejo|||0000-0001-9276-2720 Proitsi, Petroula|||0000-0002-2553-6974 Botía, Juan A.|||0000-0002-6992-598X Legido-Quigley, Cristina|||0000-0002-4018-214X Naccache, Talel Hooshmand, Kourosh Gabrielli, Martina Lombardo, Marta Tiffany ten Kate, Mara|||0000-0002-8290-8543 Frisoni, Giovanni B.|||0000-0002-6419-1753 Gualerzi, Alice Picciolini, Silvia Verderio, Claudia |
| author |
Gómez-Pascual, A.|||0000-0003-2348-9083 |
| author_facet |
Gómez-Pascual, A.|||0000-0003-2348-9083 Xu, J.|||0000-0002-6341-5938 Wretlind, A.|||0000-0001-6083-5227 Shi, L. Buckley, Noel J.|||0000-0003-1152-0653 Tijms, Betty M.|||0000-0002-2612-1797 Vos, Stephanie J.B.|||0000-0002-2045-9818 Engelborghs, Sebastiaan|||0000-0003-0304-9785 Sleegers, Kristel|||0000-0002-0283-2332 Wallin, Anders|||0000-0001-9506-0513 Lleó, Alberto|||0000-0002-2568-5478 Popp, Julius|||0000-0002-0068-0312 Martinez-Lage, P. Streffer, J. Barkhof, Frederik|||0000-0003-3543-3706 Zetterberg, Henrik|||0000-0003-3930-4354 Visser, Pieter Jelle|||0000-0001-8008-9727 Lovestone, Simon|||0000-0003-0473-4565 Bertram, Lars|||0000-0002-0108-124X Nevado-Holgado, Alejo|||0000-0001-9276-2720 Proitsi, Petroula|||0000-0002-2553-6974 Botía, Juan A.|||0000-0002-6992-598X Legido-Quigley, Cristina|||0000-0002-4018-214X Naccache, Talel Hooshmand, Kourosh Gabrielli, Martina Lombardo, Marta Tiffany ten Kate, Mara|||0000-0002-8290-8543 Frisoni, Giovanni B.|||0000-0002-6419-1753 Gualerzi, Alice Picciolini, Silvia Verderio, Claudia |
| author_role |
author |
| author2 |
Xu, J.|||0000-0002-6341-5938 Wretlind, A.|||0000-0001-6083-5227 Shi, L. Buckley, Noel J.|||0000-0003-1152-0653 Tijms, Betty M.|||0000-0002-2612-1797 Vos, Stephanie J.B.|||0000-0002-2045-9818 Engelborghs, Sebastiaan|||0000-0003-0304-9785 Sleegers, Kristel|||0000-0002-0283-2332 Wallin, Anders|||0000-0001-9506-0513 Lleó, Alberto|||0000-0002-2568-5478 Popp, Julius|||0000-0002-0068-0312 Martinez-Lage, P. Streffer, J. Barkhof, Frederik|||0000-0003-3543-3706 Zetterberg, Henrik|||0000-0003-3930-4354 Visser, Pieter Jelle|||0000-0001-8008-9727 Lovestone, Simon|||0000-0003-0473-4565 Bertram, Lars|||0000-0002-0108-124X Nevado-Holgado, Alejo|||0000-0001-9276-2720 Proitsi, Petroula|||0000-0002-2553-6974 Botía, Juan A.|||0000-0002-6992-598X Legido-Quigley, Cristina|||0000-0002-4018-214X Naccache, Talel Hooshmand, Kourosh Gabrielli, Martina Lombardo, Marta Tiffany ten Kate, Mara|||0000-0002-8290-8543 Frisoni, Giovanni B.|||0000-0002-6419-1753 Gualerzi, Alice Picciolini, Silvia Verderio, Claudia |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Universitat Autònoma de Barcelona. Departament de Medicina |
| dc.subject.none.fl_str_mv |
Alzheimer's disease Integrative omics Machine learning Metabolomics Mild cognitive impairment Proteomics |
| topic |
Alzheimer's disease Integrative omics Machine learning Metabolomics Mild cognitive impairment Proteomics |
| description |
Background: Alzheimer's disease (AD) is a neurodegenerative condition for which there is currently no available medication that can stop its progression. Previous studies suggest that mild cognitive impairment (MCI) is a phase that precedes the disease. Therefore, a better understanding of the molecular mechanisms behind MCI conversion to AD is needed. Method: Here, we propose a machine learning-based approach to detect the key metabolites and proteins involved in MCI progression to AD using data from the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery Study. Proteins and metabolites were evaluated separately in multiclass models (controls, MCI and AD) and together in MCI conversion models (MCI stable vs converter). Only features selected as relevant by 3/4 algorithms proposed were kept for downstream analysis. Results: Multiclass models of metabolites highlighted nine features further validated in an independent cohort (0.726 mean balanced accuracy). Among these features, one metabolite, oleamide, was selected by all the algorithms. Further in-vitro experiments in rodents showed that disease-associated microglia excreted oleamide in vesicles. Multiclass models of proteins stood out with nine features, validated in an independent cohort (0.720 mean balanced accuracy). However, none of the proteins was selected by all the algorithms. Besides, to distinguish between MCI stable and converters, 14 key features were selected (0.872 AUC), including tTau, alpha-synuclein (SNCA), junctophilin-3 (JPH3), properdin (CFP) and peptidase inhibitor 15 (PI15) among others. Conclusions: This omics integration approach highlighted a set of molecules associated with MCI conversion important in neuronal and glia inflammation pathways. |
| publishDate |
2024 |
| dc.date.none.fl_str_mv |
2 2024-01-01 2024 2024-01-01 |
| dc.type.none.fl_str_mv |
Article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://ddd.uab.cat/record/323202 https://dx.doi.org/urn:doi:10.1016/j.compbiomed.2024.108588 |
| url |
https://ddd.uab.cat/record/323202 https://dx.doi.org/urn:doi:10.1016/j.compbiomed.2024.108588 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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openAccess |
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application/pdf |
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reponame:Dipòsit Digital de Documents de la UAB instname:Universitat Autònoma de Barcelona |
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Universitat Autònoma de Barcelona |
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Dipòsit Digital de Documents de la UAB |
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Dipòsit Digital de Documents de la UAB |
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