Metabolic dysfunction-associated steatotic liver disease (MASLD) exhibits marked heterogeneity and sex differences, yet the molecular mechanisms underlying disease progression remain incompletely understood. Here, we present the largest integrative multi-omics study to date combining matched liver tissue and blood profiling in 211 biopsy-confirmed, morbidly obese individuals with MASLD undergoing bariatric surgery. We integrate hepatic transcriptomics, metabolomics, […]
Uncovering spatial-temporal patterns in mortality counts from pulmonary embolism in US counties between 2005 to 2022.
Pulmonary embolism (PE) is a sudden blockage of lung arteries, usually caused by a blood clot that travels from the deep veins of the legs. As the world becomes more sedentary and lifestyle diseases emerge, deaths from PE are expected to rise in the next 20 years. For instance, the United States records annual deaths […]
Calibration of in-frame indel variant effect predictors for clinical variant classification
Insertions and deletions (indels) represent a substantial source of genetic variation in humans and are associated with a diverse array of functional consequences. Despite their prevalence and clinical importance, indels, particularly short in-frame indels, remain critically understudied compared to single nucleotide variants and are challenging to interpret clinically. While many computational predictors for missense variants […]
Loneliness as a Pathway Linking Hearing Decline to Cognitive Aging: Longitudinal and Genetic Evidence
Age-related hearing loss is linked to loneliness and poorer cognitive health, but it remains unclear whether loneliness helps explain associations between hearing difficulties and cognitive performance or dementia, and whether these patterns reflect causal pathways or shared underlying liability. In this preregistered study, we triangulated analyses across multiple data sources spanning approximately 18 years of […]
A Randomized Pilot Trial of Medically Tailored Meals and Lifestyle Support for Gestational Diabetes: Feasibility, Acceptability, and Implementation Challenges
Background: Lifestyle interventions incorporating medically-tailored meal delivery may support rapid behavior change among pregnant individuals with gestational diabetes (GDM). Purpose: To examine the feasibility and acceptability of a multicomponent lifestyle intervention for pregnant individuals with GDM. Primary outcomes included recruitment, retention, intervention receipt, and acceptability. Methods: We conducted a pilot randomized feasibility trial among pregnant […]
Unscheduled bleeding and endometrial cancer in women on postmenopausal hormone replacement therapy and their matched controls: protocol for a descriptive cohort study using the Orchid-e database
Hormone replacement therapy (HRT) with oestrogen and progestogen is a common medical treatment for alleviating symptoms of menopause. Since 2015, its use has been increasing in the UK. Unscheduled bleeding can be a symptom of endometrial cancer, and guidelines state that women experiencing this should have an urgent referral for suspected endometrial cancer. However, unscheduled […]
Evaluating Individual Level Performance of Polygenic Risk Scores Using Early Onset High Genetic Risk Coronary Artery Disease as a Benchmark
Polygenic risk scores (PRSs) are typically validated using population-level metrics, masking variability in individual-level risk prediction and hindering clinical translation. To address this, we introduced a novel framework using a "benchmark" cohort (N=1184) of "unexpected coronary artery disease (CAD)": early-onset patients (<55 years) with a clinical profile of low 10-year risk, no diabetes or severe […]
Oncogenic Ras-Src-cortactin signaling rewires actin-generated forces to drive basement membrane rupture and initiate breast cancer invasion
Oncogenic HRas activation plays a fundamental role in tumorigenesis, yet the cellular mechanisms by which HRas downstream signaling drives basement membrane (BM) disruption during early breast cancer invasion remain unclear. Using HRas-inducible breast spheroids, we demonstrate that HRas rewires cellular mechanotransduction of tumor-associated extracellular matrix stiffening to promote invasion. This process occurs independently of canonical […]
LagCI Enables Inference of Temporal Causal Relationships from Dense Multi-Omic Time Series
Inferring causal relationships from time-series data is critical for uncovering the dynamics of biological regulation. However, in multi-omics studies, this task is often hampered by sparse temporal sampling and the limitations of existing methods. To address this, we developed Lagged-Correlation Based Causal Inference (lagCI), a computational framework designed to identify time-lagged associations by combining comprehensive […]
Calibration of in-frame indel variant effect predictors for clinical variant classification
Insertions and deletions (indels) represent a substantial source of genetic variation in humans and are associated with a diverse array of functional consequences. Despite their prevalence and clinical importance, indels, particularly short in-frame indels, remain critically understudied compared to single nucleotide variants and are challenging to interpret clinically. While many computational predictors for missense variants […]
Unsupervised Machine Learning for Adaptive Immune Receptors with immuneML
Machine learning (ML) enables adaptive immune receptor repertoires (AIRRs) analyses for biomarker identification and therapeutic development. With the majority of AIRR data partially or imperfectly labeled, unsupervised ML is essential for motif discovery, biologically meaningful clustering, and generation of novel receptor sequences. However, no unified framework for unsupervised ML exists in the AIRR field, hindering […]
Broadband gamma-band EEG changes during magnetophosphene perception induced by 20 Hz magnetic field stimulation
Objective. Magnetophosphenes are visual percepts induced by extremely low-frequency magnetic fields (ELF-MF; <300 Hz), yet their EEG correlates remain poorly characterized and are not reliably captured by classical low-frequency markers. We tested whether magnetophosphene perception is associated with broadband high-frequency EEG changes rather than focal oscillatory effects. Approach. EEG was recorded in N=13 healthy volunteers […]