Project description:How humans differ from one another at the molecular level and the impact of ethnicity, age and environmental factors such as diet and geography are poorly understood. To address this gap, we analyzed 322 nominally healthy individuals from diverse ethnic backgrounds located in distinct geographical regions, using (1) deep multi-omic profiling - including genome sequencing, transcriptomics, glycomics, targeted and untargeted metabolomics, lipidomics, proteomics, 16S microbiota sequencing, metaproteomics, metallomics, and metabolic hormone and pathogen profiling, (2) clinical data collection, and (3) comprehensive lifestyle surveys. Our integrative analysis revealed several key findings: associations between molecular profiles (transcripts, proteins, metabolites, lipids, glycans, and microbiota) and age, ethnicity, and geographical residence (including diet) among healthy individuals; ethnicity-specific genetic polymorphisms in key genes governing whole-body homeostasis, particularly in lipid/carbohydrate metabolism and neuroinflammation pathways; and variation in the abundance of key proteins such as the TERF2 interacting protein (TERF2IP) which is critical for cellular aging, genome stability, and protection against chromosomal degradation. These findings hold significant translational value, particularly in understanding ethnicity as a risk factor for autoimmune diseases. Many ethnicity-associated molecules identified in our study interact with existing therapeutic drugs, highlighting the potential need for ethnicity-specific drug dosing adjustments. Furthermore, our results suggest that geographical factors influence ethnic patterns, which may, in turn, affect longevity. individuals with European ancestry exhibited a lower phenotypic age, while those of Asian ancestry showed a higher phenotypic age when living outside their ancestral regions. By providing both a comprehensive baseline dataset of multi-omic variation in healthy individuals and critical insights into the molecular basis of human diversity, our study enhances our understanding of how environmental and genetic factors influence phenotypic and molecular traits and potentially augments individualized health approaches.
Project description:According to the Mainz Coping Inventory (MCI) (Krohne & Egloff, 1999) people use four main strategies for coping (i.e. Non-defensive, Repressing, High-Anxious and Sensitizing). To bridge the gap between psychology and genetics, the Affymetrix GeneChip miRNA 3.0 Array (Affymetrix, Santa Clara, USA) was used to analyze blood plasma of healthy male individuals with differing MCI coping styles to gain miRNA profiles associated with the MCI assessment and to predict biomarkers for the MCI coping modes.
Project description:Genome-wide profiling of DNA methylation in blood leukocytes from Chinese patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD). The Illumina Infinium MethylationEPIC BeadChip array (850K chip) was used to detect DNA methylation profiles throughout approximately 850,000 CpG sites in peripheral blood white cells of MCI- and AD-affected Chinese patients, as well as cognitively healthy controls. All samples included 20 Chinese patients with MCI, 20 Chinese patients with AD, and 20 cognitively healthy controls.
Project description:MicroRNAs (miRNAs) could play an important role as potential Alzheimer Disease (AD) biomarkers. Plasma samples were collected from participants: Mild cognitive impairment (MCI) due to AD patients (n= 20), preclinical AD patients (n= 8) and healthy controls (n= 20). Then, small RNA sequencing analysis, followed by miRNA differential expression analysis comparing different methods (DESeq2, edgeR, NOISeq) were carried out.
Project description:Total RNA sequencing of cultured ONS cells derived from patients with Alzheimer's disease (AD), individuals with mild cognitive impairment (MCI) and cognitively healthy controls.
Project description:Total RNA sequencing of cultured OM cells derived from patients with Alzheimer's disease (AD), individuals with mild cognitive impairment (MCI) and cognitively healthy controls.
Project description:Alzheimer's disease (AD) is the most common type of dementia. Extracellular amyloid β (Aβ) plaques and intracellular Tau-containing neurofibrillary tangles are major AD lesions that identify Alzheimer’s pathology and to neuronal loss. However, given that these structures are also seen in cognitively normal persons (healthy controls, HC) and in persons who have mild cognitive impairment (MCI), extensive efforts have been undertaken to identify other diagnostic or prognostic indicators. Here, we characterized the RNA contents of extracellular vesicles (EVs) in the plasma of age-matched individuals who are healthy or have MCI or AD. Using RNA sequencing analysis, we found that mitochondrial (mt)RNAs, including MT-ND1 through MT-ND6 and other protein-coding and noncoding mtRNAs, were strikingly elevated in MCI- and AD-associated plasma EVs compared with healthy control EVs. In cultured cells derived from astrocytes, microglia, and neurons, exposure to the toxic conditions in the AD environment (Aβ fibers and H2O2), EVs contained mitochondrial structures (as detected by electron microscopy) as well as mitochondrial RNAs. We propose that in the MCI and AD brain environment, toxicity causing mitochondrial damage results in the packaging of mitochondrial components for export in EVs, and further propose that mitochondrial RNAs in plasma EVs are robust diagnostic and prognostic markers in AD.
Project description:This dataset contains bulk RNA sequencing data from primary tumor biopsy samples of patients with prostate adenocarcinoma. TPM-normalized expression values are provided along with sample metadata. The data were generated to support transcriptomic profiling of human prostate tumors and are related to a companion single-cell RNA-seq dataset from the same cohort.
Project description:Mild cognitive impairment (MCI) is an early stage of memory loss that affects cognitive abilities, such as language or virtual/spatial comprehension. This cognitive decline is mostly ob-served with the aging of individuals. Recently, MCI has been considered as a prodromal phase of Alzheimer’s disease (AD), with a 10-15% conversion rate. However, the existing diagnostic methods fail to provide precise and well-timed diagnoses, and the pathophysiology of MCI is not fully understood. Alterations of serum N-glycan expression could represent essential con-tributors to the overall pathophysiology of neurodegenerative diseases and be used as a poten-tial marker to assess MCI diagnosis using non-invasive procedures. Herein, we undertook an LC-MS/MS glycomics approach to determine and characterize potential N-glycan markers in de-pleted blood serum samples from MCI patients. For the first time, we profiled the isomeric gly-come of the low abundant serum glycoproteins extracted from serum samples of control and MCI patients using an LC-MS/MS analytical strategy. Additionally, the MRM validation of the identified data showed five isomeric N-glycans with the ability to discriminate between healthy and MCI patients: the sialylated N-glycans HexNAc5,Hex6,Neu5Ac3 and HexNAc6,Hex7,Neu5Ac4 with single AUCs of 0.92 and 0.87 respectively, and combined AUC of 0.96; and the sialylat-ed-fucosylated N-glycans HexNAc4,Hex5,Fuc,Neu5Ac, HexNAc5,Hex6,Fuc,Neu5Ac2 and HexNAc6,Hex7,Fuc,Neu5Ac3 with single AUCs of 0.94, 0.67, and 0.88 respectively, and combined AUC of 0.98. According to ingenuity pathway analysis (IPA) and in line with recent publications the identified N-glycans may play an important role in neuroinflammation. Process that plays a fundamental role in the progression of neurodegenerative diseases.
Project description:Total RNA sequencing of cultured OM cells derived from patients with Alzheimer's disease (AD), individuals with mild cognitive impairment (MCI) and cognitively healthy controls.