Proteomics and mathematical modeling of longitudinal CSF differentiates fast versus slow ALS progression.
Journal
Annals of clinical and translational neurology
ISSN: 2328-9503
Titre abrégé: Ann Clin Transl Neurol
Pays: United States
ID NLM: 101623278
Informations de publication
Date de publication:
11 2023
11 2023
Historique:
received:
20
07
2023
accepted:
12
08
2023
medline:
16
11
2023
pubmed:
30
8
2023
entrez:
30
8
2023
Statut:
ppublish
Résumé
Amyotrophic lateral sclerosis (ALS) is a heterogeneous disease with a complex etiology that lacks biomarkers predicting disease progression. The objective of this study was to use longitudinal cerebrospinal fluid (CSF) samples to identify biomarkers that distinguish fast progression (FP) from slow progression (SP) and assess their temporal response. We utilized mass spectrometry (MS)-based proteomics to identify candidate biomarkers using longitudinal CSF from a discovery cohort of SP and FP ALS patients. Immunoassays were used to quantify and validate levels of the top biomarkers. A state-transition mathematical model was created using the longitudinal MS data that also predicted FP versus SP. We identified a total of 1148 proteins in the CSF of all ALS patients. Pathway analysis determined enrichment of pathways related to complement and coagulation cascades in FPs and synaptogenesis and glucose metabolism in SPs. Longitudinal analysis revealed a panel of 59 candidate markers that could segregate FP and SP ALS. Based on multivariate analysis, we identified three biomarkers (F12, RBP4, and SERPINA4) as top candidates that segregate ALS based on rate of disease progression. These proteins were validated in the discovery and a separate validation cohort. Our state-transition model determined that the overall variance of the proteome over time was predictive of the disease progression rate. We identified pathways and protein biomarkers that distinguish rate of ALS disease progression. A mathematical model of the CSF proteome determined that the change in entropy of the proteome over time was predictive of FP versus SP.
Identifiants
pubmed: 37646115
doi: 10.1002/acn3.51890
pmc: PMC10647001
doi:
Substances chimiques
Proteome
0
Biomarkers
0
RBP4 protein, human
0
Retinol-Binding Proteins, Plasma
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2025-2042Subventions
Organisme : NINDS NIH HHS
ID : R56 NS061867
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS061867
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA033572
Pays : United States
Informations de copyright
© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
Références
N Engl J Med. 2020 Sep 3;383(10):919-930
pubmed: 32877582
Brain Res. 2012 Aug 21;1469:114-28
pubmed: 22750125
Ann Clin Transl Neurol. 2020 Jul;7(7):1103-1116
pubmed: 32515902
Nucleic Acids Res. 2019 Jan 8;47(D1):D607-D613
pubmed: 30476243
J Neurosci Res. 2011 May;89(5):718-28
pubmed: 21337372
N Engl J Med. 2022 Sep 22;387(12):1099-1110
pubmed: 36129998
Acta Neuropathol Commun. 2020 Jun 26;8(1):92
pubmed: 32586411
Mol Neurodegener. 2018 Nov 7;13(1):60
pubmed: 30404656
J Neurol Neurosurg Psychiatry. 2019 Feb;90(2):157-164
pubmed: 30309882
Proc Natl Acad Sci U S A. 2014 Mar 18;111(11):E1035-42
pubmed: 24591593
Oncotarget. 2018 Jan 24;9(13):10847-10867
pubmed: 29541381
Elife. 2019 Jun 10;8:
pubmed: 31180318
Amyotroph Lateral Scler Frontotemporal Degener. 2015;16(7-8):456-63
pubmed: 26121274
Exp Ther Med. 2016 Jun;11(6):2095-2106
pubmed: 27284291
Muscle Nerve. 2021 Sep;64(3):309-320
pubmed: 34075589
Front Neurol. 2020 Aug 28;11:919
pubmed: 32982935
Front Neurosci. 2021 Mar 17;15:642324
pubmed: 33815045
Neurology. 2015 Jun 2;84(22):2247-57
pubmed: 25934855
Amyotroph Lateral Scler Frontotemporal Degener. 2013 Mar;14(2):146-9
pubmed: 23134506
Oxid Med Cell Longev. 2018 Dec 2;2018:4138560
pubmed: 30622668
Restor Neurol Neurosci. 2003;21(3-4):79-96
pubmed: 14530572
J Neurochem. 2019 Nov;151(3):336-350
pubmed: 31282572
Amyotroph Lateral Scler. 2012 Jan;13(1):110-8
pubmed: 22117131
Curr Genet Med Rep. 2017 Jun;5(2):108-114
pubmed: 29057168
Acta Neuropathol. 2013 Jan;125(1):111-20
pubmed: 22941226
Neurology. 2009 May 5;72(18):1614-6
pubmed: 19414730
Front Neurol. 2019 Jan 18;9:1167
pubmed: 30713520
Oxid Med Cell Longev. 2017;2017:5025610
pubmed: 28744338
Nat Neurosci. 2008 Apr;11(4):420-2
pubmed: 18344992
PLoS Comput Biol. 2017 Nov 3;13(11):e1005752
pubmed: 29099853
Muscle Nerve. 2022 Mar;65(3):291-302
pubmed: 34890069
BMC Bioinformatics. 2011 Mar 17;12:77
pubmed: 21414208
Physiol Rev. 2019 Jan 1;99(1):21-78
pubmed: 30280653
Amyotroph Lateral Scler Frontotemporal Degener. 2023 May;24(3-4):263-271
pubmed: 36106817
Nat Protoc. 2018 Mar;13(3):530-550
pubmed: 29446774
Nucleic Acids Res. 2019 Jan 8;47(D1):D442-D450
pubmed: 30395289
Cancer Res. 2020 Aug 1;80(15):3157-3169
pubmed: 32414754
Lancet. 2011 Mar 12;377(9769):942-55
pubmed: 21296405
Nature. 2016 Nov 10;539(7628):197-206
pubmed: 27830784
Bioinformatics. 2019 Mar 15;35(6):972-980
pubmed: 30165467
Int J Mol Sci. 2019 Aug 25;20(17):
pubmed: 31450699
J Neurol Neurosurg Psychiatry. 2020 Apr;91(4):350-358
pubmed: 31937582
N Engl J Med. 2020 Jul 9;383(2):109-119
pubmed: 32640130