A deep neural network to de-noise single-cell RNA sequencing data.

Single-cell RNA sequencing (scRNA-seq), a powerful technique for investigating the transcriptome of individual cells, enables the discovery of heterogeneous cell populations, rare cell types, and transcriptional dynamics in separate cells. Yet, scRNA-seq data analysis is limited by the problem of measurement dropouts, i.e.

A Meta-analysis of Transcriptome Data to Investigate the Effect of Soy Isoflavones on Breast Cancer Cell.

Background: Breast cancer ranks as the second highest cause of cancer-linked deaths in women, with varying rates between Western and Asian countries. The consumption of phytoestrogens can influence breast cancer occurrence.

Objective: To comprehend how soy isoflavones impact breast cancer cells, we conducted a meta-analysis, combining gene expression data from multiple studies.

Systematic analysis of microorganisms' metabolism for selective targeting.

Selective drugs with a relatively narrow spectrum can reduce the side effects of treatments compared to broad-spectrum antibiotics by specifically targeting the pathogens responsible for infection. Furthermore, combating an infectious pathogen, especially a drug-resistant microorganism, is more efficient by attacking multiple targets. Here, we combined synthetic lethality with selective drug targeting to identify multi-target and organism-specific potential drug candidates by systematically analyzing the genome-scale metabolic models of six different microorganisms.

Nanopore Long-Read Sequencing Unveils Genomic Disruptions in Alzheimer's Disease.

Studies in laboratory models and postmortem human brain tissue from patients with Alzheimer's disease have revealed disruption of basic cellular processes such as DNA repair and epigenetic control as drivers of neurodegeneration. While genomic alterations in regions of the genome that are rich in repetitive sequences, often termed "dark regions," are difficult to resolve using traditional sequencing approaches, long-read technologies offer promising new avenues to explore previously inaccessible regions of the genome. In the current study, we leverage nanopore-based long-read whole-genome sequencing of DNA extracted from postmortem human frontal cortex at early and late stages of Alzheimer's disease, as well as age-matched controls, to analyze retrotransposon insertion events, non-allelic homologous recombination (NAHR), structural variants and DNA methylation within retrotransposon loci and other repetitive/dark regions of the human genome.

FastKnock: an efficient next-generation approach to identify all knockout strategies for strain optimization.

Overproduction of desired native or nonnative biochemical(s) in (micro)organisms can be achieved through metabolic engineering. Appropriate rewiring of cell metabolism is performed by making rational changes such as insertion, up-/down-regulation and knockout of genes and consequently metabolic reactions. Finding appropriate targets (including proper sets of reactions to be knocked out) for metabolic engineering to design optimal production strains has been the goal of a number of computational algorithms.

Proteome Network Analysis Identifies Potential Biomarkers for Brain Aging.

Background: Alzheimer's disease and related dementias (ADRD) involve biological processes that begin years to decades before onset of clinical symptoms. The plasma proteome can offer insight into brain aging and risk of incident dementia among cognitively healthy adults.

Objective: To identify biomarkers and biological pathways associated with neuroimaging measures and incident dementia in two large community-based cohorts by applying a correlation-based network analysis to the plasma proteome.

Senolytic therapy in mild Alzheimer's disease: a phase 1 feasibility trial.

Cellular senescence contributes to Alzheimer's disease (AD) pathogenesis. An open-label, proof-of-concept, phase I clinical trial of orally delivered senolytic therapy, dasatinib (D) and quercetin (Q), was conducted in early-stage symptomatic patients with AD to assess central nervous system (CNS) penetrance, safety, feasibility and efficacy. Five participants (mean age = 76 + 5 years; 40% female) completed the 12-week pilot study.

"iNETgrate": integrating DNA methylation and gene expression data in a single gene network.

Integrating multi-omics data in one model can increase statistical power. However, designing such a model is challenging because different omics are measured at different levels. We developed the iNETgrate package (https://bioconductor.

FastKnock: An efficient next-generation approach to identify all knockout strategies for strain optimization.

Overproduction of desired native or nonnative biochemical(s) in (micro)organisms can be achieved through metabolic engineering. Appropriate rewiring of cell metabolism is performed making rational changes such as insertion, up-/down-regulation and knockout of genes and consequently metabolic reactions. Finding appropriate targets (including proper sets of reactions to be knocked out) for metabolic engineering to design optimal production strains has been the goal of a number of computational algorithms.

Senolytic therapy to modulate the progression of Alzheimer's Disease (SToMP-AD) - Outcomes from the first clinical trial of senolytic therapy for Alzheimer's disease.

Cellular senescence has been identified as a pathological mechanism linked to tau and amyloid beta (Aβ) accumulation in mouse models of Alzheimer's disease (AD). Clearance of senescent cells using the senolytic compounds dasatinib (D) and quercetin (Q) reduced neuropathological burden and improved clinically relevant outcomes in the mice. Herein, we conducted a vanguard open-label clinical trial of senolytic therapy for AD with the primary aim of evaluating central nervous system (CNS) penetrance, as well as exploratory data collection relevant to safety, feasibility, and efficacy.

The Spectrum of Alzheimer-Type Pathology in Cognitively Normal Individuals.

Background: The strongest risk factor for the development of Alzheimer's disease (AD) is age. The progression of Braak stage and Thal phase with age has been demonstrated. However, prior studies did not include cognitive status.

Rapid-SL identifies synthetic lethal sets with an arbitrary cardinality.

The multidrug resistance of numerous pathogenic microorganisms is a serious challenge that raises global healthcare concerns. Multi-target medications and combinatorial therapeutics are much more effective than single-target drugs due to their synergistic impact on the systematic activities of microorganisms. Designing efficient combinatorial therapeutics can benefit from identification of synthetic lethals (SLs).

Profiling senescent cells in human brains reveals neurons with CDKN2D/p19 and tau neuropathology.

Senescent cells contribute to pathology and dysfunction in animal models. Their sparse distribution and heterogenous phenotype have presented challenges for detecting them in human tissues. We developed a senescence eigengene approach to identify these rare cells within large, diverse populations of postmortem human brain cells.

New insights into the genetic etiology of Alzheimer's disease and related dementias.

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis.

Blood biomarkers for cognitive decline and clinical progression in a Mexican American cohort.

: The clinical translation of biofluid markers for dementia requires validation in diverse cohorts. The study goal was to evaluate if blood biomarkers reflecting diverse pathophysiological processes predict disease progression in Mexican American adults. : Mexican American adults (n = 745), 50 years of age and older, completed annual assessments over a mean of 4 years.

Differential protein expression in the hippocampi of resilient individuals identified by digital spatial profiling.

Clinical symptoms correlate with underlying neurodegenerative changes in the vast majority of people. However, an intriguing group of individuals demonstrate neuropathologic changes consistent with Alzheimer disease (AD) yet remain cognitively normal (termed "resilient"). Previous studies have reported less overall neuronal loss, less gliosis, and fewer comorbidities in these individuals.

The landscape of human tissue and cell type specific expression and co-regulation of senescence genes.

Background: Cellular senescence is a complex stress response that impacts cellular function and organismal health. Multiple developmental and environmental factors, such as intrinsic cellular cues, radiation, oxidative stress, oncogenes, and protein accumulation, activate genes and pathways that can lead to senescence. Enormous efforts have been made to identify and characterize senescence genes (SnGs) in stress and disease systems.

Molecular characterization of depression trait and state.

Major depressive disorder (MDD) is a brain disorder often characterized by recurrent episode and remission phases. The molecular correlates of MDD have been investigated in case-control comparisons, but the biological alterations associated with illness trait (regardless of clinical phase) or current state (symptomatic and remitted phases) remain largely unknown, limiting targeted drug discovery. To characterize MDD trait- and state-dependent changes, in single or recurrent depressive episode or remission, we generated transcriptomic profiles of subgenual anterior cingulate cortex of postmortem subjects in first MDD episode (n = 20), in remission after a single episode (n = 15), in recurrent episode (n = 20), in remission after recurring episodes (n = 15) and control subject (n = 20).

HspB1 Overexpression Improves Life Span and Stress Resistance in an Invertebrate Model.

To explore the role of the small heat shock protein beta 1 (HspB1, also known as Hsp25 in rodents and Hsp27 in humans) in longevity, we created a Caenorhabiditis elegans model with a high level of ubiquitous expression of the naked mole-rat HspB1 protein. The worms showed increased life span under multiple conditions and also increased resistance to heat stress. RNAi experiments suggest that HspB1-induced life extension is dependent on the transcription factors skn-1 (Nrf2) and hsf-1 (Hsf1).

DNA methylation analysis improves the prognostication of acute myeloid leukemia.

Integration of orthogonal data could provide new opportunities to pinpoint the underlying molecular mechanisms of hematologic disorders. Using a novel gene network approach, we integrated DNA methylation data from The Cancer Genome Atlas ( = 194 cases) with the corresponding gene expression profile. Our integrated gene network analysis classified AML patients into low-, intermediate-, and high-risk groups.

Blood biomarkers for dementia in Hispanic and non-Hispanic White adults.

Introduction: The study evaluated if blood markers reflecting diverse biological pathways differentiate clinical diagnostic groups among Hispanic and non-Hispanic White adults.

Methods: Within Hispanic (n = 1193) and non-Hispanic White (n = 650) participants, serum total tau (t-tau), neurofilament light (NfL), ubiquitin carboxyl-terminal hydrolase LI, glial fibrillary acidic protein (GFAP), soluble cluster of differentiation-14, and chitinase-3-like protein 1 (YKL-40) were quantified. Mixed-effects partial proportional odds ordinal logistic regression and linear mixed-effects models were used to evaluate the association of biomarkers with diagnostic group and cognition, adjusting for age, sex, ethnicity, apolipoprotein E ε4, education, and site.

The genetics of circulating BDNF: towards understanding the role of BDNF in brain structure and function in middle and old ages.

Brain-derived neurotrophic factor (BDNF) plays an important role in brain development and function. Substantial amounts of BDNF are present in peripheral blood, and may serve as biomarkers for Alzheimer's disease incidence as well as targets for intervention to reduce Alzheimer's disease risk. With the exception of the genetic polymorphism in the gene, Val66Met, which has been extensively studied with regard to neurodegenerative diseases, the genetic variation that influences circulating BDNF levels is unknown.