A5087990147- Genomics and Phylogenetic Studies
- Bioinformatics and Genomic Networks
- Gene expression and cancer classification
- Neuroinflammation and Neurodegeneration Mechanisms
- RNA and protein synthesis mechanisms
- Gut microbiota and health
- Genomics and Rare Diseases
- Diet and metabolism studies
- Alzheimer's disease research and treatments
- Single-cell and spatial transcriptomics
- Molecular Biology Techniques and Applications
- Adipose Tissue and Metabolism
- Metabolomics and Mass Spectrometry Studies
- CRISPR and Genetic Engineering
- Probiotics and Fermented Foods
- Cancer-related gene regulation
- Genetics, Aging, and Longevity in Model Organisms
- Dietary Effects on Health
- Forensic and Genetic Research
- BRCA gene mutations in cancer
- Tryptophan and brain disorders
- Salivary Gland Disorders and Functions
- Genomic variations and chromosomal abnormalities
- Interdisciplinary Research and Collaboration
- Algorithms and Data Compression
Institute for Systems Biology
2016-2025
InSysBio (Russia)
2021-2024
The Royal Free Hospital
2022
University College London
2022
Seattle University
2016-2021
North Seattle College
2018
University of Washington
1996-1997
University of Toronto
1989-1992
Alzheimer's disease (AD) is a complex neurodegenerative disorder that develops over decades. AD brain proteomics reveals vast alterations in protein levels and numerous altered biologic pathways. Here, we compare proteome network changes with the proteomes of amyloid β (Aβ)-depositing mice to identify conserved divergent networks identifying an Aβ responsome. Proteins most (M42) accumulate plaques, cerebrovascular (CAA), and/or dystrophic neuronal processes, overexpression two M42 proteins,...
The identification of microglia subtypes is important for understanding the role innate immunity in neurodegenerative diseases. Current methods unsupervised cell type assume a small noise-to-signal ratio transcriptome measurements to produce well-separated clusters. However, can be obscured by gene expression noise, which diminishes distances space between distinct types, blurs boundaries, and reduces reproducibility. Here we use Fokker-Planck (FP) diffusion maps model cellular...
We have developed an improved method of straightening DNA molecules for use in optical restriction mapping. The was straightened on 3-aminopropyl-triethoxysilane-coated glass slides using surface tension generated by a moving meniscus. In our the meniscus motion controlled mechanically, which provides advantages speed and uniformity molecules. Variation affinity silanized surfaces compensated precoating slide with single-stranded non-target blocking DNA. A small amount MgCl 2 added to...
Abstract Longitudinal multi-omics measurements are highly valuable in studying heterogeneity health and disease phenotypes. For thousands of people, we have collected longitudinal data. To analyze, interpret visualize this extremely high-dimensional data, use the Pareto Task Inference (ParTI) method. We find that clinical labs data fall within a tetrahedron. then all other types to characterize four archetypes. tetrahedron comprises three wellness states, defining triangular plane, one...
Aging manifests as progressive deteriorations in homeostasis, requiring systems-level perspectives to investigate the gradual molecular dysregulation of underlying biological processes. Here, we report systemic changes regulation processes under multiple lifespan-extending interventions. Differential Rank Conservation (DIRAC) analyses mouse liver proteomics and transcriptomics data show that mechanistically distinct interventions (acarbose, 17α-estradiol, rapamycin, calorie restriction)...
Deep sequencing of transcriptomes has become an indispensable tool for biology, enabling expression levels thousands genes to be compared across multiple samples. Since transcript counts scale with depth, from different samples must normalized a common prior comparison. We analyzed fifteen existing and novel algorithms normalizing counts, evaluated the effectiveness resulting normalizations. For this purpose we defined two mutually independent metrics: (1) number "uniform" (genes whose have...
We report a highly significant correlation in brain proteome changes between Alzheimers disease (AD) and CRND8 APP695NL/F transgenic mice. However, integrating protein observed the mice with co-expression networks derived from human AD, reveals both conserved divergent module changes. For most (M42, matrisome) we find many proteins accumulate plaques, cerebrovascular amyloid (CAA), dystrophic processes, or combination thereof. Overexpression of two M42 proteins, midkine (Mdk) pleiotrophin...
Regulation of gene expression involves the orchestrated interaction a large number proteins with transcriptional regulatory elements in context chromatin. Our understanding regulation is limited by lack protein measurement technology that can systematically detect and quantify ensemble associated specific genes. Here, we introduce set selected reaction monitoring (SRM) assays for systematic 464 known or suspected roles at RNA polymerase II transcribed promoters Saccharomyces cerevisiae....
Data normalization is a crucial step in the gene expression analysis as it ensures validity of its downstream analyses. Although many metrics have been designed to evaluate existing methods, different or datasets by same metric yield inconsistent results, particularly for single-cell RNA sequencing (scRNA-seq) data. The worst situations could be that one method evaluated best poorest another metric, using dataset dataset. Here raises an open question: principles need established guide...
Aggregation and accumulation of amyloid-β (Aβ) is a defining feature Alzheimer’s disease pathology. To study microglial responses to Aβ, we applied exogenous Aβ peptide, in either oligomeric or fibrillar conformation, primary mouse cultures evaluated system-level transcriptional changes then compared these with transcriptomic the brains CRND8 APP mice. We find that have rapid massive change response Aβ. Transcriptomic microglia, although partially overlapping, are distinct not recapitulated...
Biomedical research requires protein detection technology that is not only sensitive and quantitative, but can reproducibly measure any set of proteins in a biological system high throughput manner. Here we report the development application targeted proteomics platform termed index-ion triggered MS2 ion quantification (iMSTIQ) allows reproducible accurate peptide complex mixtures. The key feature iMSTIQ an approach called analysis (ITA) permits acquisition full spectra peptides independent...
The identification of DNA copy numbers from short-read sequencing data remains a challenge for both technical and algorithmic reasons. raw these analyses are measured in tens to hundreds gigabytes per genome; transmitting, storing, analyzing such large files is cumbersome, particularly methods that analyze several samples simultaneously. We developed very efficient representation depth coverage (150-1000× compression) enables analyses. Current variants whole-genome (WGS) frequently miss...
Human submandibular/sublingual saliva contains one non-glycosylated basic proline-rich protein whereas parotid multiple such components. The submandibular has a primary structure identical with the C-terminal segment [TZ] of human acidic proteins that contain 150 amino acid residues (Mr 16,000). Northern-blot analyses and glands revealed mRNAs containing HaeIII repeat sequence typical for are expressed in both these salivary BstN1 but not gland. Products translation vitro from were also...
We present an ultrafast method for comparing personal genomes. transform the standard genome representation (lists of variants relative to a reference) into "genome fingerprints" via locality sensitive hashing. The resulting fingerprints can be meaningfully compared even when input data were obtained using different sequencing technologies, processed pipelines, represented in formats and reference versions. Furthermore, are robust up 30% missing data. Because their reduced size, computation...
Currently, the best clinical predictor for inflammatory bowel disease (IBD) is family history. Over 163 sequence variants have been associated with IBD in genome-wide association studies, but they weak effects and explain only a fraction of observed heritability. It expected that additional contribute to genomic architecture IBD, possibly including rare effect sizes larger than identified common variants. Here we applied study design sequenced 38 individuals from five families, under...
Abstract Mapping network analysis in cells and tissues can provide insights into metabolic adaptations to changes external environment, pathological conditions, nutrient deprivation. Here, we reconstructed a genome-scale of the rat liver that will allow for exploration systems-level physiology. The resulting silico model (iRatLiver) contains 1,882 reactions, 1,448 metabolites, 994 genes. We then used this characterize response liver’s energy metabolism controlled perturbation diet....
Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin-II receptor blockers (ARB), the most commonly prescribed antihypertensive medications, counter renin-angiotensin-aldosterone system (RAAS) activation via induction of angiotensin-converting 2 (ACE2) expression. Considering that ACE2 is functional for SARS-CoV-2 entry into host cells, association ACEi ARB with COVID-19 outcomes needs thorough evaluation.We conducted retrospective analyses using both unmatched propensity score...
Abstract Translational biomedical research is generating exponentially more data: thousands of whole-genome sequences (WGS) are now available; brain data doubling every two years. Analyses Big Data, including imaging, genomic, phenotypic, and clinical data, present qualitatively new challenges as well opportunities. Among the a proliferation in ways analyses can fail, due largely to increasing length complexity processing pipelines. Anomalies input runtime resource exhaustion or node failure...
Genetic testing has expanded out of the research laboratory into medical practice and direct-to-consumer market. Rapid analysis resulting genotype data now a significant impact. We present method for summarizing personal genotypes as 'genotype fingerprints' that meets these needs. Genotype fingerprints can be derived from any single nucleotide polymorphism-based assay, remain comparable chip designs evolve to higher marker densities. demonstrate support distinguishing types relationships...
Abstract The gut microbiome has important effects on human health, yet its importance in aging remains unclear. Using two independent cohorts comprising 4582 individuals across the adult lifespan we demonstrate that, starting mid-to-late adulthood, microbiomes become increasingly unique with age. This uniqueness pattern is strongly associated microbial amino acid derivatives circulating within bloodstream, many of which have been previously identified as longevity biomarkers. At latest...
Abstract Data normalization is a crucial step in the gene expression analysis as it ensures validity of its downstream analyses. Although many metrics have been designed to evaluate current methods, different yield inconsistent results. In this study, we new metric named Area Under normalized CV threshold Curve (AUCVC) and applied with another mSCC 14 commonly used achieving consistency our evaluation results using both bulk RNA-seq scRNA-seq data from same library construction protocol....