Differential T cell clonal dynamics underlie outcomes to frontline chemoimmunotherapy in advanced gastric cancer.

The addition of aPD1 to 5-FU/platinum in advanced gastric cancer (GC) yields variable responses. To understand cooperativity between chemotherapy and immunotherapy, we previously reported a phase II trial sequentially adding pembrolizumab to 5-FU/platinum. In this study, we use single-cell RNA- and TCR-sequencing to analyze 66,813 T cells from primary tumor biopsies pre-treatment, post-chemotherapy, and post-immunotherapy in 33 patients.

Increasing temporal sensitivity of omics association studies with epigenome-wide distributed lag models.

Current methods for identifying temporal windows of effect for time-varying exposures in omics settings can control false discovery rates at the biomarker level but cannot efficiently screen for timing-specific effects in high dimensions. Current approaches leverage separate models for site screening and identification of susceptible time windows, and these can miss associations that vary over time. We introduce the epigenome-wide distributed lag model (EWDLM), a novel approach that combines traditional false discovery rate methods with the distributed lag model (DLM) to screen for timing-specific effects in high dimensional settings.

Epigenetic dysregulation in Alzheimer's disease peripheral immunity.

The peripheral immune system in Alzheimer's disease (AD) has not been thoroughly studied with modern sequencing methods. To investigate epigenetic and transcriptional alterations to the AD peripheral immune system, we used single-cell sequencing strategies, including assay for transposase-accessible chromatin and RNA sequencing. We reveal a striking amount of open chromatin in peripheral immune cells in AD.

Early Immune Remodeling Steers Clinical Response to First-Line Chemoimmunotherapy in Advanced Gastric Cancer.

Unlabelled: Adding anti-programmed cell death protein 1 (anti-PD-1) to 5-fluorouracil (5-FU)/platinum improves survival in some advanced gastroesophageal adenocarcinomas (GEA). To understand the effects of chemotherapy and immunotherapy, we conducted a phase II first-line trial (n = 47) sequentially adding pembrolizumab to 5-FU/platinum in advanced GEA. Using serial biopsy of the primary tumor at baseline, after one cycle of 5-FU/platinum, and after the addition of pembrolizumab, we transcriptionally profiled 358,067 single cells to identify evolving multicellular tumor microenvironment (TME) networks.

Spatial analysis of human lung cancer reveals organized immune hubs enriched for stem-like CD8 T cells and associated with immunotherapy response.

The organization of immune cells in human tumors is not well understood. Immunogenic tumors harbor spatially-localized multicellular 'immunity hubs' defined by expression of the T cell-attracting chemokines and abundant T cells. Here, we examined immunity hubs in human pre-immunotherapy lung cancer specimens, and found that they were associated with beneficial responses to PD-1-blockade.

Epigenome-wide association of neonatal methylation and trimester-specific prenatal PM exposure.

Unlabelled: Exposure to particulate matter with an aerodynamic diameter smaller than 2.5 microns (PM) can affect birth outcomes through physiological pathways such as inflammation. One potential way PM affects physiology could be through altering DNA methylation (DNAm).

User-Centered Evaluation of a Visual Annotation Tool for Rapid Assessment of Pediatric Weight Entry Errors.

Weight entry errors can cause significant patient harm in pediatrics due to pervasive weight-based dosing practices. While computerized algorithms can assist in error detection, they have not achieved high sensitivity and specificity to be further developed as a clinical decision support tool. To train an advanced algorithm, expert-annotated weight errors are essential but difficult to collect.

Objective and Automated Detection of Diffuse White Matter Abnormality in Preterm Infants Using Deep Convolutional Neural Networks.

Diffuse white matter abnormality (DWMA), or diffuse excessive high signal intensity is observed in 50-80% of very preterm infants at term-equivalent age. It is subjectively defined as higher than normal signal intensity in periventricular and subcortical white matter in comparison to normal unmyelinated white matter on T-weighted MRI images. Despite the well-documented presence of DWMA, it remains debatable whether DWMA represents pathological tissue injury or a transient developmental phenomenon.

Enhancing Diagnosis of Autism With Optimized Machine Learning Models and Personal Characteristic Data.

Autism spectrum disorder (ASD) is a developmental disorder, affecting about 1% of the global population. Currently, the only clinical method for diagnosing ASD are standardized ASD tests which require prolonged diagnostic time and increased medical costs. Our objective was to explore the predictive power of personal characteristic data (PCD) from a large well-characterized dataset to improve upon prior diagnostic models of ASD.