MotivationCross-species analysis of large-scale protein–protein interaction (PPI) networks has played a significant role in understanding the principles deriving evolution of cellular organizations and functions. Recently, network alignment algorithms have been proposed to predict conserved interactions and functions of proteins. These approaches are based on the notion that orthologous proteins across species are sequentially similar and that topology of PPIs between orthologs is often conserved. However, high accuracy and scalability of network alignment are still a challenge.ResultsWe propose a novel pairwise global network alignment algorithm, called PrimAlign, which is modeled as a Markov chain and iteratively transited until convergence. The proposed algorithm also incorporates the principles of PageRank. This approach is evaluated on tasks with human, yeast and fruit fly PPI networks. The experimental results demonstrate that PrimAlign outperforms several prevalent methods with statistically significant differences in multiple evaluation measures. PrimAlign, which is multi-platform, achieves superior performance in runtime with its linear asymptotic time complexity. Further evaluation is done with synthetic networks and results suggest that popular topological measures do not reflect real precision of alignments.Availability and implementationThe source code is available at http://web.ecs.baylor.edu/faculty/cho/PrimAlign.Supplementary information Supplementary data are available at Bioinformatics online.
Background: Metabolites are biological compounds reflecting the functional activity of organs and tissues. Understanding metabolic changes in Alzheimer’s disease (AD) can provide insight into potential risk factors in this multifactorial disease and suggest new intervention strategies or improve non-invasive diagnosis. Objective: In this study, we searched for changes in AD metabolism in plasma and frontal brain cortex tissue samples and evaluated the performance of plasma measurements as biomarkers. Methods: This is a case-control study with two tissue cohorts: 158 plasma samples (94 AD, 64 controls; Texas Alzheimer’s Research and Care Consortium – TARCC) and 71 postmortem cortex samples (35 AD, 36 controls; Banner Sun Health Research Institute brain bank). We performed targeted mass spectrometry analysis of 630 compounds (106 small molecules: UHPLC-MS/MS, 524 lipids: FIA-MS/MS) and 232 calculated metabolic indicators with a metabolomic kit (Biocrates MxP® Quant 500). Results: We discovered disturbances (FDR≤0.05) in multiple metabolic pathways in AD in both cohorts including microbiome-related metabolites with pro-toxic changes, methylhistidine metabolism, polyamines, corticosteroids, omega-3 fatty acids, acylcarnitines, ceramides, and diglycerides. In AD, plasma reveals elevated triglycerides, and cortex shows altered amino acid metabolism. A cross-validated diagnostic prediction model from plasma achieves AUC = 82% (CI95 = 75–88%); for females specifically, AUC = 88% (CI95 = 80–95%). A reduced model using 20 features achieves AUC = 79% (CI95 = 71–85%); for females AUC = 84% (CI95 = 74–92%). Conclusion: Our findings support the involvement of gut environment in AD and encourage targeting multiple metabolic areas in the design of intervention strategies, including microbiome composition, hormonal balance, nutrients, and muscle homeostasis.
Disruptions in one-carbon metabolism and elevated homocysteine have been previously implicated in the development of dementia associated with Alzheimer’s disease (AD) and Parkinson’s disease (PD). Moreover, a PD diagnosis itself carries substantial risk for the development of dementia. This is the first study that explores alterations in one-carbon metabolism in AD and PD directly in the human brain frontal cortex, the primary center of cognition. Applying targeted liquid chromatography–tandem mass spectrometry (LC-MS/MS), we analyzed post-mortem samples obtained from 136 subjects (35 AD, 65 PD, 36 controls). We found changes in one-carbon metabolites that indicate inefficient activation of cystathionine β-synthase (CBS) in AD and PD subjects with dementia, the latter seemingly accompanied by a restricted re-methylation flow. Levodopa–carbidopa is known to reduce available vitamin B6, which would explain the hindered CBS activity. We present evidence of temporary non-protein-bound homocysteine accumulation upon levodopa intake in the brain of PD subjects with dementia but not in non-demented PD subjects. Importantly, this homocysteine elevation is not related to levodopa dosage, disease progression, or histopathological markers but exclusively to the dementia status. We hypothesize that this levodopa-induced effect is a direct cause of dementia in PD in susceptible subjects with reduced re-methylation capacity. Furthermore, we show that betaine best correlates with cognitive score even among PD subjects alone and discuss nutritional recommendations to improve one-carbon metabolism function.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.