Molecular subgroups of ALS patients with distinct survival outcomes identified through plasma proteomics
Aksoylu, I. S.; Azizi, L.; Öijerstedt, L.; Lilja, S.; Alvez, M. B.; Yazdani, S.; Skoglund, L.; Foucher, J.; Juto, A.; Seitz, C.; Press, R.; Samuelsson, K.; Kläppe, U.; Fang, F.; Uhlen, M.; Edfors, F.; Nilsson, P.; Ingre, C.; Manberg, A.
Show abstract
Amyotrophic Lateral Sclerosis (ALS) is a phenotypically diverse neurodegenerative disorder characterized by the degeneration of motor neurons, ultimately resulting in loss of motor function. Currently, patients are classified based on clinical factors which does not fully capture the heterogeneity. Using the Olink Explore HT, we pro-filed ~5400 plasma proteins in ALS patients (n = 235) from the ALSrisc Study at Karolinska Institutet, Sweden, and applied consensus clustering, which revealed three patient subgroups significantly differing in survival outcome. Weighted gene correlation network analysis (WGCNA) and gene ontology (GO) analysis identified protein modules related to biological functions including cellular stress response and Rho-GTPase activity for the shorter surviving patient group. Cell-type enrichment analysis indicating a broad cellular origin of the circulating proteome, with contributions from nervous system cells, vascular cells, immune cells, and muscle cells. Our work highlights the potential of plasma proteomics for clinically meaningful patient stratification in ALS.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Network Analysis of the Cerebrospinal Fluid Proteome Reveals Shared and Unique Differences Between Sporadic and Familial Forms of Amyotrophic Lateral Sclerosis 94%
- Decoding distinctive features of plasma extracellular vesicles in amyotrophic lateral sclerosis 93%
- A Microglial Activity State Biomarker Panel Differentiates Ftd-Granulin And Ad From Control Cases 93%
Similar papers in this journal
- Genoppi: an open-source software for robust and standardized integration of proteomic and genetic data 92%
- Translocator protein is a marker of activated microglia in rodent models but not human neurodegenerative diseases 92%
- Cell type-specific biotin labeling in vivo resolves regional neuronal proteomic differences in mouse brain 91%
Similar papers in this journal
- miRNA biomarkers for diagnosis of ALS and FTD, developed by a nonlinear machine learning approach 92%
- Image-based deep learning reveals the responses of human motor neurons to stress and ALS 91%
- SFPQ intron retention, reduced expression and aggregate formation in central nervous system tissue are pathological features of amyotrophic lateral sclerosis 90%
Similar papers in this journal
- Synaptic proteomics reveal distinct molecular signatures of cognitive change and C9ORF72 repeat expansion in the human ALS cortex 94%
- Comparative profiling of the synaptic proteome from Alzheimer’s disease patients with focus on the APOE genotype 92%
- White adipose tissue undergoes pathological dysfunction in the TDP-43A315T mouse model of amyotrophic lateral sclerosis (ALS) 92%
Similar papers in this journal
- Single-cell transcriptomic landscape of the neuroimmune compartment in amyotrophic lateral sclerosis brain and spinal cord 92%
- Nuclear depletion of RNA binding protein ELAVL3 (HuC) in sporadic and familial amyotrophic lateral sclerosis 92%
- TMEM106B modifies TDP-43 pathology in human ALS brain and cell-based models of TDP-43 proteinopathy 91%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.