A Mechanistic, Stochastic Model Helps Understand Multiple Sclerosis Course and Pathogenesis
Heritable and nonheritable factors play a role in multiple sclerosis, but their effect size appears too small, explaining relatively little about disease etiology. Assuming that the factors that trigger the onset of the disease are, to some extent, also those that generate its remissions and relapse...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2013-01-01
|
| Series: | International Journal of Genomics |
| Online Access: | http://dx.doi.org/10.1155/2013/910321 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832552573163274240 |
|---|---|
| author | Isabella Bordi Renato Umeton Vito A. G. Ricigliano Viviana Annibali Rosella Mechelli Giovanni Ristori Francesca Grassi Marco Salvetti Alfonso Sutera |
| author_facet | Isabella Bordi Renato Umeton Vito A. G. Ricigliano Viviana Annibali Rosella Mechelli Giovanni Ristori Francesca Grassi Marco Salvetti Alfonso Sutera |
| author_sort | Isabella Bordi |
| collection | DOAJ |
| description | Heritable and nonheritable factors play a role in multiple sclerosis, but their effect size appears too small, explaining relatively little about disease etiology. Assuming that the factors that trigger the onset of the disease are, to some extent, also those that generate its remissions and relapses, we attempted to model the erratic behaviour of the disease course as observed on a dataset containing the time series of relapses and remissions of 70 patients free of disease-modifying therapies. We show that relapses and remissions follow exponential decaying distributions, excluding periodic recurrences and confirming that relapses manifest randomly in time. It is found that a mechanistic model with a random forcing describes in a satisfactory manner the occurrence of relapses and remissions, and the differences in the length of time spent in each one of the two states. This model may describe how interactions between “soft” etiologic factors occasionally reach the disease threshold thanks to comparably small external random perturbations. The model offers a new context to rethink key problems such as “missing heritability” and “hidden environmental structure” in the etiology of complex traits. |
| format | Article |
| id | doaj-art-7c6876a8adc0411b8e3936b3cc4ed0a1 |
| institution | Kabale University |
| issn | 2314-436X 2314-4378 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Genomics |
| spelling | doaj-art-7c6876a8adc0411b8e3936b3cc4ed0a12025-02-03T05:58:18ZengWileyInternational Journal of Genomics2314-436X2314-43782013-01-01201310.1155/2013/910321910321A Mechanistic, Stochastic Model Helps Understand Multiple Sclerosis Course and PathogenesisIsabella Bordi0Renato Umeton1Vito A. G. Ricigliano2Viviana Annibali3Rosella Mechelli4Giovanni Ristori5Francesca Grassi6Marco Salvetti7Alfonso Sutera8Department of Physics, Sapienza University of Rome, Piazzale Aldo Moro 2, 00185 Rome, ItalyCentre for Experimental Neurological Therapies (CENTERS), Neurology and Department of Neurosciences, Mental Health and Sensory Organs, S. Andrea Hospital, Sapienza University of Rome, via di Grottarossa 1035-1039, 00189 Rome, ItalyCentre for Experimental Neurological Therapies (CENTERS), Neurology and Department of Neurosciences, Mental Health and Sensory Organs, S. Andrea Hospital, Sapienza University of Rome, via di Grottarossa 1035-1039, 00189 Rome, ItalyCentre for Experimental Neurological Therapies (CENTERS), Neurology and Department of Neurosciences, Mental Health and Sensory Organs, S. Andrea Hospital, Sapienza University of Rome, via di Grottarossa 1035-1039, 00189 Rome, ItalyCentre for Experimental Neurological Therapies (CENTERS), Neurology and Department of Neurosciences, Mental Health and Sensory Organs, S. Andrea Hospital, Sapienza University of Rome, via di Grottarossa 1035-1039, 00189 Rome, ItalyCentre for Experimental Neurological Therapies (CENTERS), Neurology and Department of Neurosciences, Mental Health and Sensory Organs, S. Andrea Hospital, Sapienza University of Rome, via di Grottarossa 1035-1039, 00189 Rome, ItalyDepartment of Physiology and Pharmacology, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, ItalyCentre for Experimental Neurological Therapies (CENTERS), Neurology and Department of Neurosciences, Mental Health and Sensory Organs, S. Andrea Hospital, Sapienza University of Rome, via di Grottarossa 1035-1039, 00189 Rome, ItalyDepartment of Physics, Sapienza University of Rome, Piazzale Aldo Moro 2, 00185 Rome, ItalyHeritable and nonheritable factors play a role in multiple sclerosis, but their effect size appears too small, explaining relatively little about disease etiology. Assuming that the factors that trigger the onset of the disease are, to some extent, also those that generate its remissions and relapses, we attempted to model the erratic behaviour of the disease course as observed on a dataset containing the time series of relapses and remissions of 70 patients free of disease-modifying therapies. We show that relapses and remissions follow exponential decaying distributions, excluding periodic recurrences and confirming that relapses manifest randomly in time. It is found that a mechanistic model with a random forcing describes in a satisfactory manner the occurrence of relapses and remissions, and the differences in the length of time spent in each one of the two states. This model may describe how interactions between “soft” etiologic factors occasionally reach the disease threshold thanks to comparably small external random perturbations. The model offers a new context to rethink key problems such as “missing heritability” and “hidden environmental structure” in the etiology of complex traits.http://dx.doi.org/10.1155/2013/910321 |
| spellingShingle | Isabella Bordi Renato Umeton Vito A. G. Ricigliano Viviana Annibali Rosella Mechelli Giovanni Ristori Francesca Grassi Marco Salvetti Alfonso Sutera A Mechanistic, Stochastic Model Helps Understand Multiple Sclerosis Course and Pathogenesis International Journal of Genomics |
| title | A Mechanistic, Stochastic Model Helps Understand Multiple Sclerosis Course and Pathogenesis |
| title_full | A Mechanistic, Stochastic Model Helps Understand Multiple Sclerosis Course and Pathogenesis |
| title_fullStr | A Mechanistic, Stochastic Model Helps Understand Multiple Sclerosis Course and Pathogenesis |
| title_full_unstemmed | A Mechanistic, Stochastic Model Helps Understand Multiple Sclerosis Course and Pathogenesis |
| title_short | A Mechanistic, Stochastic Model Helps Understand Multiple Sclerosis Course and Pathogenesis |
| title_sort | mechanistic stochastic model helps understand multiple sclerosis course and pathogenesis |
| url | http://dx.doi.org/10.1155/2013/910321 |
| work_keys_str_mv | AT isabellabordi amechanisticstochasticmodelhelpsunderstandmultiplesclerosiscourseandpathogenesis AT renatoumeton amechanisticstochasticmodelhelpsunderstandmultiplesclerosiscourseandpathogenesis AT vitoagricigliano amechanisticstochasticmodelhelpsunderstandmultiplesclerosiscourseandpathogenesis AT vivianaannibali amechanisticstochasticmodelhelpsunderstandmultiplesclerosiscourseandpathogenesis AT rosellamechelli amechanisticstochasticmodelhelpsunderstandmultiplesclerosiscourseandpathogenesis AT giovanniristori amechanisticstochasticmodelhelpsunderstandmultiplesclerosiscourseandpathogenesis AT francescagrassi amechanisticstochasticmodelhelpsunderstandmultiplesclerosiscourseandpathogenesis AT marcosalvetti amechanisticstochasticmodelhelpsunderstandmultiplesclerosiscourseandpathogenesis AT alfonsosutera amechanisticstochasticmodelhelpsunderstandmultiplesclerosiscourseandpathogenesis AT isabellabordi mechanisticstochasticmodelhelpsunderstandmultiplesclerosiscourseandpathogenesis AT renatoumeton mechanisticstochasticmodelhelpsunderstandmultiplesclerosiscourseandpathogenesis AT vitoagricigliano mechanisticstochasticmodelhelpsunderstandmultiplesclerosiscourseandpathogenesis AT vivianaannibali mechanisticstochasticmodelhelpsunderstandmultiplesclerosiscourseandpathogenesis AT rosellamechelli mechanisticstochasticmodelhelpsunderstandmultiplesclerosiscourseandpathogenesis AT giovanniristori mechanisticstochasticmodelhelpsunderstandmultiplesclerosiscourseandpathogenesis AT francescagrassi mechanisticstochasticmodelhelpsunderstandmultiplesclerosiscourseandpathogenesis AT marcosalvetti mechanisticstochasticmodelhelpsunderstandmultiplesclerosiscourseandpathogenesis AT alfonsosutera mechanisticstochasticmodelhelpsunderstandmultiplesclerosiscourseandpathogenesis |