Identification of molecular signatures and pathways to identify novel therapeutic targets in Alzheimer's disease: Insights from a systems biomedicine perspective

Rahman, Rezanur; Islam, Tania; Zaman, Toyfiquz; Shahjaman, Md.; Karim, Md. Rezaul; Huq, Fazlul; Quinn, Julian M.W.; Holsinger, R. M. Damian; Göv, Esra; Moni, Mohammad Ali

doi:10.1016/j.ygeno.2019.07.018

Cited by 111 publications

(71 citation statements)

References 64 publications

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“…The most highly ranked pathway was the ribosomal pathway. Similar to this finding, the ribosomal pathway was also enriched in a network analysis that was performed using other datasets (GSE4226 and GSE4229) [64]. The ribosomal pathway was also significantly enriched in the differentially expressed genes from the neuronal dataset GSE4757 [65].…”

Section: Discussionsupporting

confidence: 59%

Meta-Analysis of Gene Expression Changes in the Blood of Patients with Mild Cognitive Impairment and Alzheimer’s Disease Dementia

Bottero

Potashkin

2019

IJMS

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Background: Dementia is a major public health concern affecting approximately 47 million people worldwide. Mild cognitive impairment (MCI) is one form of dementia that affects an individual’s memory with or without affecting their daily life. Alzheimer’s disease dementia (ADD) is a more severe form of dementia that usually affects elderly individuals. It remains unclear whether MCI is a distinct disorder from or an early stage of ADD. Methods: Gene expression data from blood were analyzed to identify potential biomarkers that may be useful for distinguishing between these two forms of dementia. Results: A meta-analysis revealed 91 genes dysregulated in individuals with MCI and 387 genes dysregulated in ADD. Pathway analysis identified seven pathways shared between MCI and ADD and nine ADD-specific pathways. Fifteen transcription factors were associated with MCI and ADD, whereas seven transcription factors were specific for ADD. Mir-335-5p was specific for ADD, suggesting that it may be useful as a biomarker. Diseases that are associated with MCI and ADD included developmental delays, cognition impairment, and movement disorders. Conclusion: These results provide a better molecular understanding of peripheral changes that occur in MCI and ADD patients and may be useful in the identification of diagnostic and prognostic biomarkers.

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Section: Discussionsupporting

confidence: 59%

Meta-Analysis of Gene Expression Changes in the Blood of Patients with Mild Cognitive Impairment and Alzheimer’s Disease Dementia

Bottero

Potashkin

2019

IJMS

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“…Changes in gene expression are widely studied to characterize various human diseases and successfully used to predict molecular and cellular processes in complex diseases [ 2 , 3 ]. Recently, some studies have been focused ASD pathogenesis to decode gene expression signatures specific for ASD.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Analysis of RNA-Seq Gene Expression Profiling of Brain Transcriptomes Reveals Novel Genes, Regulators, and Pathways in Autism Spectrum Disorder

et al. 2020

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Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with deficits in social communication ability and repetitive behavior. The pathophysiological events involved in the brain of this complex disease are still unclear. Methods: In this study, we aimed to profile the gene expression signatures of brain cortex of ASD patients, by using two publicly available RNA-seq studies, in order to discover new ASD-related genes. Results: We detected 1567 differentially expressed genes (DEGs) by meta-analysis, where 1194 were upregulated and 373 were downregulated genes. Several ASD-related genes previously reported were also identified. Our meta-analysis identified 235 new DEGs that were not detected using the individual RNA-seq studies used. Some of those genes, including seven DEGs (PAK1, DNAH17, DOCK8, DAPP1, PCDHAC2, and ERBIN, SLC7A7), have been confirmed in previous reports to be associated with ASD. Gene Ontology (GO) and pathways analysis showed several molecular pathways enriched by the DEGs, namely, osteoclast differentiation, TNF signaling pathway, complement and coagulation cascade. Topological analysis of protein–protein interaction of the ASD brain cortex revealed proteomics hub gene signatures: MYC, TP53, HDAC1, CDK2, BAG3, CDKN1A, GABARAPL1, EZH2, VIM, and TRAF1. We also identified the transcriptional factors (TFs) regulating DEGs, namely, FOXC1, GATA2, YY1, FOXL1, USF2, NFIC, NFKB1, E2F1, TFAP2A, HINFP. Conclusion: Novel core genes and molecular signatures involved with ASD were identified by our meta-analysis.

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“…Of the miRNAs retrieved, only "MIRLET7B" (referred to in the text as Let-7b) was associated with oxidative stress. Elevated levels of Let-7b have been detected in AD patients [113], and it was further identified as a blood-based molecular biomarker signature in AD [114]. However, we found no literature connecting Let-7b and OGG1 despite this indirect association depicted by the network generated by DES-ROD.…”

Section: Oxidative Medicine and Cellular Longevitymentioning

confidence: 64%

DES-ROD: Exploring Literature to Develop New Links between RNA Oxidation and Human Diseases

Essack

Salhi

Neste

et al. 2020

Oxidative Medicine and Cellular Longevity

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Normal cellular physiology and biochemical processes require undamaged RNA molecules. However, RNAs are frequently subjected to oxidative damage. Overproduction of reactive oxygen species (ROS) leads to RNA oxidation and disturbs redox (oxidation-reduction reaction) homeostasis. When oxidation damage affects RNA carrying protein-coding information, this may result in the synthesis of aberrant proteins as well as a lower efficiency of translation. Both of these, as well as imbalanced redox homeostasis, may lead to numerous human diseases. The number of studies on the effects of RNA oxidative damage in mammals is increasing by year due to the understanding that this oxidation fundamentally leads to numerous human diseases. To enable researchers in this field to explore information relevant to RNA oxidation and effects on human diseases, we developed DES-ROD, an online knowledgebase that contains processed information from 298,603 relevant documents that consist of PubMed abstracts and PubMed Central full-text articles. The system utilizes concepts/terms from 38 curated thematic dictionaries mapped to the analyzed documents. Researchers can explore enriched concepts, as well as enriched pairs of putatively associated concepts. In this way, one can explore mutual relationships between any combinations of two concepts from used dictionaries. Dictionaries cover a wide range of biomedical topics, such as human genes and proteins, pathways, Gene Ontology categories, mutations, noncoding RNAs, enzymes, toxins, metabolites, and diseases. This makes insights into different facets of the effects of RNA oxidation and the control of this process possible. The usefulness of the DES-ROD system is demonstrated by case studies on some known information, as well as potentially novel information involving RNA oxidation and diseases. DES-ROD is the first knowledgebase based on text and data mining that focused on the exploration of RNA oxidation and human diseases.

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Identification of molecular signatures and pathways to identify novel therapeutic targets in Alzheimer's disease: Insights from a systems biomedicine perspective

Cited by 111 publications

References 64 publications

Meta-Analysis of Gene Expression Changes in the Blood of Patients with Mild Cognitive Impairment and Alzheimer’s Disease Dementia

Meta-Analysis of Gene Expression Changes in the Blood of Patients with Mild Cognitive Impairment and Alzheimer’s Disease Dementia

Comprehensive Analysis of RNA-Seq Gene Expression Profiling of Brain Transcriptomes Reveals Novel Genes, Regulators, and Pathways in Autism Spectrum Disorder

DES-ROD: Exploring Literature to Develop New Links between RNA Oxidation and Human Diseases

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