Conceptual model of the MAMELI Project.

<div><p>The concept of the exposome encompasses all the factors influencing human health throughout the life course. The exposome induces epigenetic changes, such as DNA methylation, which influence gene expression and impact overall health. Several recent studies have explored how repet...

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المؤلف الرئيسي: Valentina Bollati (106778) (author)
مؤلفون آخرون: Federica Rota (4431574) (author), Laura Dioni (3110841) (author), Chiara Favero (4002554) (author), Simona Iodice (4431580) (author), Marta Gallazzi (21688455) (author), Andrea Spinazzè (2811298) (author), Giacomo Fanti (18550699) (author), Davide Campagnolo (2811301) (author), Tiago Nardi (19668803) (author), Davide Biganzoli (21688458) (author), Eva Dariol (21688461) (author), Rachele Matsagani (21688464) (author), Mirjam Hoxha (106799) (author), Paola Monti (218762) (author), Benedetta Albetti (113773) (author), Letizia Tarantini (157035) (author), Davide Barbuto (21688467) (author), Ester Luconi (10023058) (author), Giuseppe Marano (842579) (author), Giacomo Biganzoli (20431424) (author), Roberta Biciuffi (21688470) (author), Patrizia Boracchi (563422) (author), Domenico M. Cavallo (2811295) (author), Pilar M. Guerrieri (21688473) (author), Fabio Mosca (295673) (author), Stefano Gustincich (169690) (author), Giovanni Sanesi (12075190) (author), Luca Ferrari (3749722) (author), Michele Carugno (154960) (author), Silvia Fustinoni (10147910) (author), Angela Cecilia Pesatori (10971846) (author), Luca Pandolfini (3568151) (author), Michele Miragoli (251842) (author), Andrea Cattaneo (366170) (author), Elia Biganzoli (563427) (author)
منشور في: 2025
الموضوعات:
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_version_ 1852018618485702656
author Valentina Bollati (106778)
author2 Federica Rota (4431574)
Laura Dioni (3110841)
Chiara Favero (4002554)
Simona Iodice (4431580)
Marta Gallazzi (21688455)
Andrea Spinazzè (2811298)
Giacomo Fanti (18550699)
Davide Campagnolo (2811301)
Tiago Nardi (19668803)
Davide Biganzoli (21688458)
Eva Dariol (21688461)
Rachele Matsagani (21688464)
Mirjam Hoxha (106799)
Paola Monti (218762)
Benedetta Albetti (113773)
Letizia Tarantini (157035)
Davide Barbuto (21688467)
Ester Luconi (10023058)
Giuseppe Marano (842579)
Giacomo Biganzoli (20431424)
Roberta Biciuffi (21688470)
Patrizia Boracchi (563422)
Domenico M. Cavallo (2811295)
Pilar M. Guerrieri (21688473)
Fabio Mosca (295673)
Stefano Gustincich (169690)
Giovanni Sanesi (12075190)
Luca Ferrari (3749722)
Michele Carugno (154960)
Silvia Fustinoni (10147910)
Angela Cecilia Pesatori (10971846)
Luca Pandolfini (3568151)
Michele Miragoli (251842)
Andrea Cattaneo (366170)
Elia Biganzoli (563427)
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
author
author
author
author
author_facet Valentina Bollati (106778)
Federica Rota (4431574)
Laura Dioni (3110841)
Chiara Favero (4002554)
Simona Iodice (4431580)
Marta Gallazzi (21688455)
Andrea Spinazzè (2811298)
Giacomo Fanti (18550699)
Davide Campagnolo (2811301)
Tiago Nardi (19668803)
Davide Biganzoli (21688458)
Eva Dariol (21688461)
Rachele Matsagani (21688464)
Mirjam Hoxha (106799)
Paola Monti (218762)
Benedetta Albetti (113773)
Letizia Tarantini (157035)
Davide Barbuto (21688467)
Ester Luconi (10023058)
Giuseppe Marano (842579)
Giacomo Biganzoli (20431424)
Roberta Biciuffi (21688470)
Patrizia Boracchi (563422)
Domenico M. Cavallo (2811295)
Pilar M. Guerrieri (21688473)
Fabio Mosca (295673)
Stefano Gustincich (169690)
Giovanni Sanesi (12075190)
Luca Ferrari (3749722)
Michele Carugno (154960)
Silvia Fustinoni (10147910)
Angela Cecilia Pesatori (10971846)
Luca Pandolfini (3568151)
Michele Miragoli (251842)
Andrea Cattaneo (366170)
Elia Biganzoli (563427)
author_role author
dc.creator.none.fl_str_mv Valentina Bollati (106778)
Federica Rota (4431574)
Laura Dioni (3110841)
Chiara Favero (4002554)
Simona Iodice (4431580)
Marta Gallazzi (21688455)
Andrea Spinazzè (2811298)
Giacomo Fanti (18550699)
Davide Campagnolo (2811301)
Tiago Nardi (19668803)
Davide Biganzoli (21688458)
Eva Dariol (21688461)
Rachele Matsagani (21688464)
Mirjam Hoxha (106799)
Paola Monti (218762)
Benedetta Albetti (113773)
Letizia Tarantini (157035)
Davide Barbuto (21688467)
Ester Luconi (10023058)
Giuseppe Marano (842579)
Giacomo Biganzoli (20431424)
Roberta Biciuffi (21688470)
Patrizia Boracchi (563422)
Domenico M. Cavallo (2811295)
Pilar M. Guerrieri (21688473)
Fabio Mosca (295673)
Stefano Gustincich (169690)
Giovanni Sanesi (12075190)
Luca Ferrari (3749722)
Michele Carugno (154960)
Silvia Fustinoni (10147910)
Angela Cecilia Pesatori (10971846)
Luca Pandolfini (3568151)
Michele Miragoli (251842)
Andrea Cattaneo (366170)
Elia Biganzoli (563427)
dc.date.none.fl_str_mv 2025-07-09T17:40:17Z
dc.identifier.none.fl_str_mv 10.1371/journal.pone.0326467.g001
dc.relation.none.fl_str_mv https://figshare.com/articles/figure/Conceptual_model_of_the_MAMELI_Project_/29522916
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Medicine
Genetics
Cancer
Science Policy
Environmental Sciences not elsewhere classified
Biological Sciences not elsewhere classified
two time points
three main phases
several recent studies
plastic entities capable
influence gene expression
developing personalized interventions
mameli project proposes
mameli project offers
environmental triggers could
original 200 participants
200 healthy participants
res (&# 8220
impact overall health
mameli cohort study
mameli project
200 participants
environmental impact
500 participants
&# 8220
study protocol
intervention study
mameli algorithm
environmental stimuli
environmental health
environmental changes
xlink ">
values predicted
separate cohort
responding physiologically
repetitive elements
powerful tool
novel perspective
life course
individual health
include 2
identifying individuals
health resilience
generation sequencing
enroll 6
embedded within
disease prevention
always detrimental
700 subjects
6 months
dc.title.none.fl_str_mv Conceptual model of the MAMELI Project.
dc.type.none.fl_str_mv Image
Figure
info:eu-repo/semantics/publishedVersion
image
description <div><p>The concept of the exposome encompasses all the factors influencing human health throughout the life course. The exposome induces epigenetic changes, such as DNA methylation, which influence gene expression and impact overall health. Several recent studies have explored how repetitive elements (REs) in the genome can be activated in response to environmental stimuli. However, most of these investigations have assumed that altered RE methylation is always detrimental to individual health. The MAMELI project proposes an alternative hypothesis: that some REs are plastic entities capable of responding physiologically to environmental stimuli without compromising genome stability. This hypothesis suggests that the ability of DNA to adapt to environmental triggers could be monitored and used as an indicator of health resilience. To test this hypothesis, the MAMELI project will enroll 6,200 participants from the city of Legnano (Italy) and will be conducted in three main phases: i) A total of 200 healthy participants will undergo DNA methylation analysis through third-generation sequencing at two time points: T0 (baseline) and T1 (6 months after T0). This phase aims to identify a set of REs (“differential REs”) whose methylation changes in response to the exposome without affecting genome stability; ii) This phase will include 2,700 subjects (the original 200 participants from the discovery phase plus 2,500 additional subjects). The goal will be to develop a predictive algorithm (the MAMELI algorithm) that links the exposome to RE methylation status, creating a “RE methylation signature” reflecting the environmental impact on DNA methylation; iii) In this phase, the MAMELI algorithm will be applied to a separate cohort of 3,500 participants to compare the measured RE methylation signature with values predicted by the algorithm. Additionally, an intervention study will be embedded within the cohort to assess the reversibility of RE methylation following lifestyle changes. The MAMELI project offers a novel perspective in the field of epigenetics and environmental health, demonstrating how the epigenome can act as a sensor for environmental changes and how this interaction can be harnessed for disease prevention. If validated, the MAMELI algorithm could become a powerful tool for identifying individuals at risk and developing personalized interventions to improve global health outcomes.</p></div>
eu_rights_str_mv openAccess
id Manara_dcdaa618f4425ee7391c4f7b40ccfc5d
identifier_str_mv 10.1371/journal.pone.0326467.g001
network_acronym_str Manara
network_name_str ManaraRepo
oai_identifier_str oai:figshare.com:article/29522916
publishDate 2025
repository.mail.fl_str_mv
repository.name.fl_str_mv
repository_id_str
rights_invalid_str_mv CC BY 4.0
spelling Conceptual model of the MAMELI Project.Valentina Bollati (106778)Federica Rota (4431574)Laura Dioni (3110841)Chiara Favero (4002554)Simona Iodice (4431580)Marta Gallazzi (21688455)Andrea Spinazzè (2811298)Giacomo Fanti (18550699)Davide Campagnolo (2811301)Tiago Nardi (19668803)Davide Biganzoli (21688458)Eva Dariol (21688461)Rachele Matsagani (21688464)Mirjam Hoxha (106799)Paola Monti (218762)Benedetta Albetti (113773)Letizia Tarantini (157035)Davide Barbuto (21688467)Ester Luconi (10023058)Giuseppe Marano (842579)Giacomo Biganzoli (20431424)Roberta Biciuffi (21688470)Patrizia Boracchi (563422)Domenico M. Cavallo (2811295)Pilar M. Guerrieri (21688473)Fabio Mosca (295673)Stefano Gustincich (169690)Giovanni Sanesi (12075190)Luca Ferrari (3749722)Michele Carugno (154960)Silvia Fustinoni (10147910)Angela Cecilia Pesatori (10971846)Luca Pandolfini (3568151)Michele Miragoli (251842)Andrea Cattaneo (366170)Elia Biganzoli (563427)MedicineGeneticsCancerScience PolicyEnvironmental Sciences not elsewhere classifiedBiological Sciences not elsewhere classifiedtwo time pointsthree main phasesseveral recent studiesplastic entities capableinfluence gene expressiondeveloping personalized interventionsmameli project proposesmameli project offersenvironmental triggers couldoriginal 200 participants200 healthy participantsres (&# 8220impact overall healthmameli cohort studymameli project200 participantsenvironmental impact500 participants&# 8220study protocolintervention studymameli algorithmenvironmental stimulienvironmental healthenvironmental changesxlink ">values predictedseparate cohortresponding physiologicallyrepetitive elementspowerful toolnovel perspectivelife courseindividual healthinclude 2identifying individualshealth resiliencegeneration sequencingenroll 6embedded withindisease preventionalways detrimental700 subjects6 months<div><p>The concept of the exposome encompasses all the factors influencing human health throughout the life course. The exposome induces epigenetic changes, such as DNA methylation, which influence gene expression and impact overall health. Several recent studies have explored how repetitive elements (REs) in the genome can be activated in response to environmental stimuli. However, most of these investigations have assumed that altered RE methylation is always detrimental to individual health. The MAMELI project proposes an alternative hypothesis: that some REs are plastic entities capable of responding physiologically to environmental stimuli without compromising genome stability. This hypothesis suggests that the ability of DNA to adapt to environmental triggers could be monitored and used as an indicator of health resilience. To test this hypothesis, the MAMELI project will enroll 6,200 participants from the city of Legnano (Italy) and will be conducted in three main phases: i) A total of 200 healthy participants will undergo DNA methylation analysis through third-generation sequencing at two time points: T0 (baseline) and T1 (6 months after T0). This phase aims to identify a set of REs (“differential REs”) whose methylation changes in response to the exposome without affecting genome stability; ii) This phase will include 2,700 subjects (the original 200 participants from the discovery phase plus 2,500 additional subjects). The goal will be to develop a predictive algorithm (the MAMELI algorithm) that links the exposome to RE methylation status, creating a “RE methylation signature” reflecting the environmental impact on DNA methylation; iii) In this phase, the MAMELI algorithm will be applied to a separate cohort of 3,500 participants to compare the measured RE methylation signature with values predicted by the algorithm. Additionally, an intervention study will be embedded within the cohort to assess the reversibility of RE methylation following lifestyle changes. The MAMELI project offers a novel perspective in the field of epigenetics and environmental health, demonstrating how the epigenome can act as a sensor for environmental changes and how this interaction can be harnessed for disease prevention. If validated, the MAMELI algorithm could become a powerful tool for identifying individuals at risk and developing personalized interventions to improve global health outcomes.</p></div>2025-07-09T17:40:17ZImageFigureinfo:eu-repo/semantics/publishedVersionimage10.1371/journal.pone.0326467.g001https://figshare.com/articles/figure/Conceptual_model_of_the_MAMELI_Project_/29522916CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/295229162025-07-09T17:40:17Z
spellingShingle Conceptual model of the MAMELI Project.
Valentina Bollati (106778)
Medicine
Genetics
Cancer
Science Policy
Environmental Sciences not elsewhere classified
Biological Sciences not elsewhere classified
two time points
three main phases
several recent studies
plastic entities capable
influence gene expression
developing personalized interventions
mameli project proposes
mameli project offers
environmental triggers could
original 200 participants
200 healthy participants
res (&# 8220
impact overall health
mameli cohort study
mameli project
200 participants
environmental impact
500 participants
&# 8220
study protocol
intervention study
mameli algorithm
environmental stimuli
environmental health
environmental changes
xlink ">
values predicted
separate cohort
responding physiologically
repetitive elements
powerful tool
novel perspective
life course
individual health
include 2
identifying individuals
health resilience
generation sequencing
enroll 6
embedded within
disease prevention
always detrimental
700 subjects
6 months
status_str publishedVersion
title Conceptual model of the MAMELI Project.
title_full Conceptual model of the MAMELI Project.
title_fullStr Conceptual model of the MAMELI Project.
title_full_unstemmed Conceptual model of the MAMELI Project.
title_short Conceptual model of the MAMELI Project.
title_sort Conceptual model of the MAMELI Project.
topic Medicine
Genetics
Cancer
Science Policy
Environmental Sciences not elsewhere classified
Biological Sciences not elsewhere classified
two time points
three main phases
several recent studies
plastic entities capable
influence gene expression
developing personalized interventions
mameli project proposes
mameli project offers
environmental triggers could
original 200 participants
200 healthy participants
res (&# 8220
impact overall health
mameli cohort study
mameli project
200 participants
environmental impact
500 participants
&# 8220
study protocol
intervention study
mameli algorithm
environmental stimuli
environmental health
environmental changes
xlink ">
values predicted
separate cohort
responding physiologically
repetitive elements
powerful tool
novel perspective
life course
individual health
include 2
identifying individuals
health resilience
generation sequencing
enroll 6
embedded within
disease prevention
always detrimental
700 subjects
6 months