A5055598960- Genetic Associations and Epidemiology
- Gut microbiota and health
- Genetic Mapping and Diversity in Plants and Animals
- Bioinformatics and Genomic Networks
- Genomics and Phylogenetic Studies
- Genetics, Aging, and Longevity in Model Organisms
- Microbial Community Ecology and Physiology
- Obstructive Sleep Apnea Research
- Health, Environment, Cognitive Aging
- Insect symbiosis and bacterial influences
- Nutrition, Genetics, and Disease
- Heat shock proteins research
- Ocular Oncology and Treatments
- Developmental Biology and Gene Regulation
- Sleep and related disorders
- Neurobiology and Insect Physiology Research
- Sleep and Wakefulness Research
- Retinal Development and Disorders
- Genetic and phenotypic traits in livestock
- Reproductive Biology and Fertility
- Insect and Pesticide Research
- Water Treatment and Disinfection
- Viral Infectious Diseases and Gene Expression in Insects
- Wastewater Treatment and Nitrogen Removal
- Folate and B Vitamins Research
Brigham and Women's Hospital
2021-2024
Harvard University
2021-2024
Weizmann Institute of Science
2014-2024
Circadian (United States)
2021-2023
Sheba Medical Center
2023
Toyota Technological Institute at Chicago
2013
Tel Aviv University
2008-2013
Most of our knowledge about the remarkable microbial diversity on Earth comes from sequencing 16S rRNA gene. The use next-generation methods has increased sample number and depth, but read length most widely used platforms today is quite short, requiring researcher to choose a subset gene sequence (typically 16–33% total length). Thus, many bacteria may share same amplified region, resolution profiling inherently limited. Platforms that offer ultra-long lengths, whole genome shotgun...
Abstract Unlike vertically transmitted endosymbionts, which have broad effects on their host’s germ line, the extracellular gut microbiota is horizontally and not known to influence line. Here we provide evidence supporting of these bacteria line Drosophila melanogaster . Removal represses oogenesis, expedites maternal-to-zygotic-transition in offspring unmasks hidden phenotypic variation mutants. We further show that main impact oogenesis linked lack Acetobacter species, identify Aldehyde...
Polygenic risk scores (PRS) are commonly used to quantify the inherited susceptibility for a trait, yet they fail account non-linear and interaction effects between single nucleotide polymorphisms (SNPs). We address this via machine learning approach, validated in nine complex phenotypes multi-ancestry population. use an ensemble method of SNP selection followed by gradient boosted trees (XGBoost) allow non-linearities effects. compare our results standard, linear PRS model developed using...
Throughout the developing central nervous system, pre-patterning of ventricular zone into discrete neural progenitor domains is one predominant strategies used to produce neuronal diversity in a spatially coordinated manner. In retina, neurogenesis proceeds an intricate chronological and spatial sequence, yet it remains unclear whether retinal cells (RPCs) display intrinsic heterogeneity at any given time point. Here, we performed detailed study RPC fate upon temporally confined inactivation...
Commensal gut bacteria in many species including flies are integral part of their host, and known to influence its development homeostasis within generation. Here we report an unexpected impact host-microbe interactions, which mediates multi-generational, non-Mendelian inheritance a stress-induced phenotype. We have previously shown that exposure fly larvae G418 antibiotic induces transgenerationally heritable phenotypes, delay larval development, gene induction the morphological changes....
During the lifetime of an organism, every individual encounters many combinations diverse changes in somatic genome, epigenome and microbiome. This gives rise to novel internal failures which are unique each individual. How any can tolerate this high load new, individual-specific scenarios failure is not clear. While stress-induced plasticity hidden variation have been proposed as potential mechanisms tolerance, main conceptual problem remains unaddressed, namely: how largely non-beneficial...
Gut microbiota have been shown to promote oogenesis and fecundity, but the mechanistic basis of remote influence on remained unknown. Here, we report a systemic mechanism mediated by bacterial-derived supply mitochondrial coenzymes. Removal decreased activity ATP levels in whole-body ovary, resulting repressed oogenesis. Similar repression was caused RNA-based knockdown function ovarian follicle cells. Reduced germ-free (GF) females reversed bacterial recolonization or supplementation...
Obstructive Sleep Apnoea (OSA) often co-occurs with cardiometabolic and pulmonary diseases. This study is to apply genetic analysis methods explain the associations between OSA related phenotypes.In Hispanic Community Healthy Study/Study of Latinos, we estimated correlations ρg respiratory event index (REI) 54 anthropometric, glycemic, cardiometabolic, phenotypes. We used summary statistics from published genome-wide association studies construct Polygenic Risk Scores (PRSs) representing...
The emergence of massively parallel sequencing technology has revolutionized microbial profiling, allowing the unprecedented comparison diversity across time and space in a wide range host-associated environmental ecosystems. Although high-throughput nature such methods enables detection low-frequency bacteria, these advances come at cost read length, limiting phylogenetic resolution possible by current methods. Here, we present generic approach for integrating short reads from large genomic...
The coupling between cell-cycle exit and onset of differentiation is a common feature throughout the developing nervous system, but mechanisms that link these processes are mostly unknown. Although transcription factor Pax6 has been implicated in both proliferation multiple regions within central system (CNS), its contribution to transition successive states remains elusive. To gain insight into role during from proliferating progenitors differentiating precursors, we investigated...
Abstract We construct non-linear machine learning (ML) prediction models for systolic and diastolic blood pressure (SBP, DBP) using demographic clinical variables polygenic risk scores (PRSs). developed a two-model ensemble, consisting of baseline model, where is based on only, genetic we also include PRSs. evaluate the use linear versus model at both levels assess improvement in performance when incorporating multiple report ensemble model’s as percentage variance explained (PVE) held-out...
Abstract Background Most of our knowledge about the remarkable microbial diversity on Earth comes from sequencing 16S rRNA gene. The use next-generation methods has increased sample number and depth, but read length most widely used platforms today is quite short, requiring researcher to choose a subset gene sequence (typically 16-33% total length). Thus, many bacteria may share same amplified region resolution profiling inherently limited. Platforms that offer ultra long lengths, whole...
It is becoming increasingly clear that most, if not all, animals and plants are associated with a diverse array of resident gut microbiota. This symbiosis regulated by host‐microbiome interactions which influence the development, homeostasis, adaptation evolution host. Recent evidence indicated these can also affect host germline have potential supporting transgenerational effects, including inheritance acquired characteristics. Taken together, bacteria on soma could potentially give rise to...
BackgroundThe human microbiome is linked to multiple metabolic disorders such as obesity and diabetes. Obstructive sleep apnoea (OSA) a common disorder with several risk factors. We investigated the associations between gut composition function, measures of OSA severity in participants from prospective community-based cohort study: Hispanic Community Health Study/Study Latinos (HCHS/SOL).MethodsBacterial-Wide Association Analysis (BWAS) measured via metagenomics was performed adjusting for...
Tertiary wastewater treatment could provide a reliable source of water for reuse. Amongst these types treatment, deep-bed filtration secondary effluents can effectively remove particles and organic matter; however, NH4+ NO2− are not easily removed. This study examined the feasibility stimulating microbial activity using hydrogen peroxide (H2O2) as bio-specific clean oxygen that leaves no residuals in is advantageous upon aeration due to solubility limitations oxygen. The performance pilot...
Genetic correlation refers to the between genetic determinants of a pair traits. When using individual-level data, it is typically estimated based on bivariate model specification where two variables identifiable and can be from covariance that incorporates relationship individuals, e.g., pre-specified kinship matrix. Inference relying asymptotic normality parameter estimates may inaccurate when sample size low, close boundary space, heritability at least one traits low. We address this...
Despite significant progress in understanding epigenetic reprogramming of cells, the mechanistic basis "organ reprogramming" by (epi-)gene-environment interactions remained largely obscure. Here, we use ether-induced haltere-to-wing transformations Drosophila as a model for "reprogramming" at whole organism level. Our findings support chain events explaining why and how brief embryonic exposure to ether leads manifested larval stage on. We show that interferes with protein integrity egg,...
Abstract Polygenic risk scores (PRS) are commonly used to quantify the inherited susceptibility for a given trait. However, standard PRS fail account non-linear and interaction effects between single nucleotide polymorphisms (SNPs). Machine learning algorithms can be such non-linearities interactions. We trained validated polygenic prediction models five complex phenotypes in multi-ancestry population: total cholesterol, triglycerides, systolic blood pressure, sleep duration, height. an...
Abstract We developed novel closed-form estimators of genetic and environmental correlation coefficients. applied them to estimate over 4,000 correlations between multiple phenotypes in a diverse sample from the Trans-Omics Precision Medicine (TOPMed) program. found substantial differences heritabilities, genetic, phenotype-pairs Black, Hispanic/Latino White populations as well sexes. Finally, we quantified phenotypic domains, each characterized by phenotypes. Altogether provide novel,...
Abstract Microbiome studies have become integral to a wide range of biological research from ecology oncology, mainly relying on short-read sequencing variable regions along the 16S rRNA gene. However, comprehensiveness has been persistently challenged due lack primer universality and biases, causing differences between study’s results underlying bacterial community. Moreover, small part gene often provides low phylogenetic resolution, hampering downstream taxonomy-based analysis ability...
Abstract Genetic correlation refers to the between genetic determinants of a pair traits. When using individual-level data, it is typically estimated based on bivariate model specification where two variables identifiable and can be from covariance that incorporates relationship individuals, e.g., pre-specified kinship matrix. Inference relying asymptotic normality parameter estimates may inaccurate when sample size low, close boundary space, heritability at least one traits low. We address...