A Dynamic Bayesian Network model for the simulation of Amyotrophic Lateral Sclerosis progression.

A Dynamic Bayesian Network model for the simulation of Amyotrophic Lateral Sclerosis progression.

Publication date: Apr 18, 2019

Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease progressively affecting upper and lower motor neurons in the brain and spinal cord. Mean life expectancy is three to five years, with paralysis of muscles, respiratory failure and loss of vital functions being the common causes of death. Clinical manifestations of ALS are heterogeneous due to the mix of anatomic regions involvement and the variability in disease course; consequently, diagnosis and prognosis at the level of individual patient is really challenging. Prediction of ALS progression and stratification of patients into meaningful subgroups have been long-standing interests to clinical practice, research and drug development.

We developed a Dynamic Bayesian Network (DBN) model on more than 4500 ALS patients included in the Pooled Resource Open-Access ALS Clinical Trials Database (PRO-ACT), in order to detect probabilistic relationships among clinical variables and identify risk factors related to survival and loss of vital functions. Furthermore, the DBN was used to simulate the temporal evolution of an ALS cohort predicting survival and the time to impairment of vital functions (communication, swallowing, gait and respiration). A first attempt to stratify patients by risk factors and simulate the progression of ALS subgroups was also implemented.

The DBN model provided the prediction of ALS most probable trajectories over time in terms of important clinical outcomes, including survival and loss of autonomy in functional domains. Furthermore, it allowed the identification of biomarkers related to patients’ clinical status as well as vital functions, and unrevealed their probabilistic relationships. For instance, DBN found that bicarbonate and calcium levels influence survival time; moreover, the model evidenced dependencies over time among phosphorus level, movement impairment and creatinine. Finally, our model provided a tool to stratify patients into subgroups of different prognosis studying the effect of specific variables, or combinations of them, on either survival time or time to loss of autonomy in specific functional domains.

The analysis of the risk factors and the simulation allowed by our DBN model might enable better support for ALS prognosis as well as a deeper insight into disease manifestations, in a context of a personalized medicine approach.

Open Access PDF

Zandon`a, A., Vasta, R., Chi`o, A., and Di Camillo, B. A Dynamic Bayesian Network model for the simulation of Amyotrophic Lateral Sclerosis progression. 04442. 2019 BMC Bioinformatics (20):Suppl 4.

Concepts Keywords
ACT Simulation
ALS Drug development
Amyotrophic Lateral Sclerosis DBN
Bicarbonate RTT
Biomarkers Dynamic Bayesian network
BMC Rare diseases
Brain Amyotrophic lateral sclerosis
Calcium Nervous system
Cohort Neurodegenerative disorders
Creatinine Neurological disorders
Drug Development Respiratory failure
Evolution Lateral sclerosis ALS
Gait
Motor Neurons
Neurodegenerative
Open Access
Paralysis
Phosphorus
Probabilistic
Prognosis
Respiration
Respiratory Failure
Simulation
Spinal Cord
Stratification

Semantics

Type Source Name
gene UNIPROT SOAT1
gene UNIPROT F11R
disease MESH Sleep disorders
gene UNIPROT CASP8
gene UNIPROT MAX
gene UNIPROT NOC2L
disease MESH neuron degeneration
drug DRUGBANK Iron
gene UNIPROT TNIP1
gene UNIPROT BRD2
gene UNIPROT COL9A3
gene UNIPROT COMP
gene UNIPROT COL9A1
gene UNIPROT COL9A2
gene UNIPROT SCN8A
gene UNIPROT EXOG
disease DOID BDC
gene UNIPROT ERAL1
gene UNIPROT ESR1
disease MESH Sclerosis
disease MESH community
gene UNIPROT SSRP1
gene UNIPROT COX5A
gene UNIPROT COX8A
gene UNIPROT CPOX
gene UNIPROT DNMT1
gene UNIPROT CD69
gene UNIPROT CD5L
drug DRUGBANK L-Valine
gene UNIPROT WLS
gene UNIPROT INPP5D
gene UNIPROT ELP1
disease MESH respiratory acidosis
gene UNIPROT ELL
disease MESH men
gene UNIPROT DEPP1
gene UNIPROT GOPC
gene UNIPROT FBLIM1
drug DRUGBANK Saquinavir
gene UNIPROT TNFRSF11A
gene UNIPROT TNMD
gene UNIPROT CYLD
drug DRUGBANK Tretamine
gene UNIPROT SARS2
gene UNIPROT ADI1
gene UNIPROT SULT1E1
gene UNIPROT MAP3K8
drug DRUGBANK Coenzyme M
gene UNIPROT PLEKHG5
gene UNIPROT HOMER2
gene UNIPROT CPD
gene UNIPROT PFDN1
gene UNIPROT PDF
gene UNIPROT GDF15
gene UNIPROT CYGB
drug DRUGBANK Potassium cation
gene UNIPROT GGT1
drug DRUGBANK Creatine
gene UNIPROT DYRK3
gene UNIPROT IK
drug DRUGBANK Nitrogen
drug DRUGBANK Urea
drug DRUGBANK Alkaline Phosphatase
gene UNIPROT SLC17A5
drug DRUGBANK L-Alanine
gene UNIPROT NT5E
gene UNIPROT GRAP2
gene UNIPROT ABCC8
gene UNIPROT PSMB6
gene UNIPROT YY1
gene UNIPROT DLL1
gene UNIPROT ARTN
gene UNIPROT AGRP
gene UNIPROT INA
gene UNIPROT DAG1
gene UNIPROT ELK3
gene UNIPROT EPHB1
gene UNIPROT SLC6A2
drug DRUGBANK Aspartame
gene UNIPROT SET
disease MESH multiple
gene UNIPROT TNFSF13
gene UNIPROT ANP32B
gene UNIPROT KCNIP3
drug DRUGBANK Riluzole
gene UNIPROT LARGE1
disease MESH complications
gene UNIPROT RASL12
gene UNIPROT SNAP25
gene UNIPROT HERPUD1
gene UNIPROT MENT
drug DRUGBANK Trestolone
gene UNIPROT PTPN5
gene UNIPROT ARNTL
gene UNIPROT PSD4
disease MESH tic
gene UNIPROT PRPF6
disease MESH dysphagia
gene UNIPROT KIDINS220
disease MESH difficulty walking
disease MESH defects
pathway BSID Metabolism
gene UNIPROT MAGEE1
disease DOID lateral sclerosis
disease MESH lateral sclerosis
disease MESH death
drug DRUGBANK Tropicamide
drug DRUGBANK Creatinine
drug DRUGBANK Phosphorus
drug DRUGBANK Calcium
disease MESH gait
disease MESH risk factors
gene UNIPROT FHL5
gene UNIPROT POTEM
gene UNIPROT ACTG1
gene UNIPROT SERPINA3
gene UNIPROT ACTBL2
gene UNIPROT ACTG2
gene UNIPROT ACOT7
disease MESH development
disease MESH diagnosis
gene UNIPROT MIXL1
disease MESH causes of death
disease DOID respiratory failure
disease MESH respiratory failure
disease MESH paralysis
disease DOID neurodegenerative disease
disease MESH neurodegenerative disease
gene UNIPROT SOD1
gene UNIPROT IGFALS
disease DOID Amyotrophic Lateral Sclerosis
disease MESH Amyotrophic Lateral Sclerosis

Original Article

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