Placental network differences among obstetric syndromes identified with an integrated multiomics approach.

The placenta is essential for pregnancy, and its dysfunction can harm both mother and fetus. To better understand placental physiology and its disruption in disease, we employ a multiomics approach (transcriptomics, metabolomics, and proteomics) combined with clinical data and histopathology from 321 placentas across conditions: severe fetal growth restriction (FGR), FGR with hypertension (FGR + HDP), severe preeclampsia (PE), and spontaneous preterm delivery (PTD). Cellular deconvolution reveals FGR + HDP placentas have more extravillous trophoblasts than controls (p < 0.

genotype and biological age impact inter-omic associations related to bioenergetics.

Apolipoprotein E () modifies human aging; specifically, the ε2 and ε4 alleles are among the strongest genetic predictors of longevity and Alzheimer's disease (AD) risk, respectively. However, detailed mechanisms for their influence on aging remain unclear. In the present study, we analyzed multi-omic association patterns across genotypes, sex, and biological age (BA) axes in 2,229 community dwelling individuals.

Altered huntingtin-chromatin interactions predict transcriptional and epigenetic changes in Huntington's disease.

While progressive striatal gene expression changes and epigenetic alterations are a prominent feature of Huntington's disease (HD), the mechanistic basis remains poorly understood. Using chromatin immunoprecipitation and sequencing (ChIP-seq), we show that the huntingtin protein (HTT) reproducibly occupies specific locations in the mouse genome. Striatal HTT ChIP-seq peaks were enriched in coding regions of spiny projection neuron identity genes that were found to have reduced expression in HD patients and mouse models, and had reduced occupancy in expanded polyglutamine HTT knock-in mice (HttQ111/Q111).

Genotype and Biological Age Impact Inter-Omic Associations Related to Bioenergetics.

Apolipoprotein E ( ) modifies human aging; specifically, the ε2 and ε4 alleles are among the strongest genetic predictors of longevity and Alzheimer's disease (AD) risk, respectively. However, detailed mechanisms for their influence on aging remain unclear. Herein, we analyzed inter-omic, context-dependent association patterns across genotypes, sex, and health axes in 2,229 community-dwelling individuals to test genotypes for variation in metabolites and metabolite-associations tied to a previously-validated metric of biological aging (BA) based on blood biomarkers.

Multi-Omic characterization of the effects of Ocrelizumab in patients with relapsing-remitting multiple sclerosis.

The study examined changes in the plasma proteome, metabolome, and lipidome of N = 14 patients with relapsing-remitting multiple sclerosis (RRMS) initiating treatment with ocrelizumab, assayed at baseline, 6 months, and 12 months. Analyses of >4000 circulating biomarkers identified depletion of B-cell associated proteins as the early effect observed following ocrelizumab (OCR) initiation, accompanied by the reduction in plasma abundance of cytokines and cytotoxic proteins, markers of neuronaxonal damage, and biologically active lipids including ceramides and lysophospholipids, at 6 months. B-cell depletion was accompanied by decreases in B-cell receptor and cytokine signaling but a pronounced increase in circulating plasma B-cell activating factor (BAFF).

A genome scale transcriptional regulatory model of the human placenta.

Gene regulation is essential to placental function and fetal development. We built a genome-scale transcriptional regulatory network (TRN) of the human placenta using digital genomic footprinting and transcriptomic data. We integrated 475 transcriptomes and 12 DNase hypersensitivity datasets from placental samples to globally and quantitatively map transcription factor (TF)-target gene interactions.

Timing of selective serotonin reuptake inhibitor use and risk for preterm birth and related adverse events: with a consideration of the COVID-19 pandemic period.

Objective: There is uncertainty around the safety of SSRIs for treating depression during pregnancy. Nevertheless, the use of SSRIs has been gradually increasing, especially during the COVID-19 pandemic period. We aimed to (1) characterize maternal depression rate and use of SSRIs in a recent 10-year period, (2) address confounding by indication, as well as socioeconomic and environmental factors, and (3) evaluate associations of the timing of SSRI exposure in pregnancy with risk for preterm birth (PTB), low birthweight (LBW), and small for gestational age (SGA) infants among women with depression before pregnancy.

The transition from genomics to phenomics in personalized population health.

Modern health care faces several serious challenges, including an ageing population and its inherent burden of chronic diseases, rising costs and marginal quality metrics. By assessing and optimizing the health trajectory of each individual using a data-driven personalized approach that reflects their genetics, behaviour and environment, we can start to address these challenges. This assessment includes longitudinal phenome measures, such as the blood proteome and metabolome, gut microbiome composition and function, and lifestyle and behaviour through wearables and questionnaires.

Integrated unbiased multiomics defines disease-independent placental clusters in common obstetrical syndromes.

Background: Placental dysfunction, a root cause of common syndromes affecting human pregnancy, such as preeclampsia (PE), fetal growth restriction (FGR), and spontaneous preterm delivery (sPTD), remains poorly defined. These common, yet clinically disparate obstetrical syndromes share similar placental histopathologic patterns, while individuals within each syndrome present distinct molecular changes, challenging our understanding and hindering our ability to prevent and treat these syndromes.

Methods: Using our extensive biobank, we identified women with severe PE (n = 75), FGR (n = 40), FGR with a hypertensive disorder (FGR + HDP; n = 33), sPTD (n = 72), and two uncomplicated control groups, term (n = 113), and preterm without PE, FGR, or sPTD (n = 16).

Effect of COVID-19 vaccination and booster on maternal-fetal outcomes: a retrospective cohort study.

Background: COVID-19 in pregnant people increases the risk for poor maternal-fetal outcomes. However, COVID-19 vaccination hesitancy remains due to concerns over the vaccine's potential effects on maternal-fetal outcomes. Here we examine the impact of COVID-19 vaccination and boosters on maternal SARS-CoV-2 infections and birth outcomes.

Healthy aging and the human gut microbiome: why we cannot just turn back the clock.

The aging research field has largely focused on reversing aging-related changes in the body. However, emerging evidence about the gut microbiome indicates that it may not be optimal to just turn back the clock. Here, we advocate for a more tailored and function-focused approach promoting health across the lifespan.

Multiomic signatures of body mass index identify heterogeneous health phenotypes and responses to a lifestyle intervention.

Multiomic profiling can reveal population heterogeneity for both health and disease states. Obesity drives a myriad of metabolic perturbations and is a risk factor for multiple chronic diseases. Here we report an atlas of cross-sectional and longitudinal changes in 1,111 blood analytes associated with variation in body mass index (BMI), as well as multiomic associations with host polygenic risk scores and gut microbiome composition, from a cohort of 1,277 individuals enrolled in a wellness program (Arivale).

The impact of maternal SARS-CoV-2 infection and COVID-19 vaccination on maternal-fetal outcomes.

The rapidly evolving COVID-19 pandemic has resulted in an upsurge of scientific productivity to help address the global health crisis. One area of active research is the impact of COVID-19 on pregnancy. Here, we provide an epidemiological overview about what is known about the effects of maternal SARS-CoV-2 infection and COVID-19 vaccination on maternal-fetal outcomes, and identify gaps in knowledge.

Multi-Omic analyses characterize the ceramide/sphingomyelin pathway as a therapeutic target in Alzheimer's disease.

Dysregulation of sphingomyelin and ceramide metabolism have been implicated in Alzheimer's disease. Genome-wide and transcriptome-wide association studies have identified various genes and genetic variants in lipid metabolism that are associated with Alzheimer's disease. However, the molecular mechanisms of sphingomyelin and ceramide disruption remain to be determined.

The effect of COVID-19 vaccination and booster on maternal-fetal outcomes: a retrospective multicenter cohort study.

Background: COVID-19 infection in pregnant people has previously been shown to increase the risk for poor maternal-fetal outcomes. Despite this, there has been a lag in COVID-19 vaccination in pregnant people due to concerns over the potential effects of the vaccine on maternal-fetal outcomes. Here we examine the impact of COVID-19 vaccination and booster on maternal COVID-19 breakthrough infections and birth outcomes.

A Wipe-Based Stool Collection and Preservation Kit for Microbiome Community Profiling.

While a range of methods for stool collection exist, many require complicated, self-directed protocols and stool transfer. In this study, we introduce and validate a novel, wipe-based approach to fecal sample collection and stabilization for metagenomics analysis. A total of 72 samples were collected across four different preservation types: freezing at -20°C, room temperature storage, a commercial DNA preservation kit, and a dissolvable wipe used with DESS (dimethyl sulfoxide, ethylenediaminetetraacetic acid, sodium chloride) solution.

Heterogeneity in statin responses explained by variation in the human gut microbiome.

Background: Statins remain one of the most prescribed medications worldwide. While effective in decreasing atherosclerotic cardiovascular disease risk, statin use is associated with adverse effects for a subset of patients, including disrupted metabolic control and increased risk of type 2 diabetes.

Methods: We investigated the potential role of the gut microbiome in modifying patient responses to statin therapy across two independent cohorts (discovery n = 1,848, validation n = 991).

Risk factors for severe COVID-19 differ by age for hospitalized adults.

Risk stratification for hospitalized adults with COVID-19 is essential to inform decisions about individual patients and allocation of resources. So far, risk models for severe COVID outcomes have included age but have not been optimized to best serve the needs of either older or younger adults. Models also need to be updated to reflect improvements in COVID-19 treatments.

Personal Dense Dynamic Data Clouds Connect Systems Biomedicine to Scientific Wellness.

The dramatic convergence of molecular biology, genomics, proteomics, metabolomics, bioinformatics, and artificial intelligence has provided a substrate for deep understanding of the biological basis of health and disease. Systems biology is a holistic, dynamic, integrative, cross-disciplinary approach to biological complexity that embraces experimentation, technology, computation, and clinical translation. Systems Medicine integrates genome analyses and longitudinal deep phenotyping with biological pathways and networks to understand mechanisms of disease, identify relevant blood biomarkers, define druggable molecular targets, and enhance the maintenance or restoration of wellness.