High-resolution reconstruction of cell-type specific transcriptional regulatory processes from bulk sequencing samples.

Biological systems exhibit remarkable heterogeneity, characterized by intricate interplay among diverse cell types. Resolving the regulatory processes of specific cell types is crucial for delineating developmental mechanisms and disease etiologies. While single-cell sequencing methods such as scRNA-seq and scATAC-seq have revolutionized our understanding of individual cellular functions, adapting bulk genome-wide assays to achieve single-cell resolution of other genomic features remains a significant technical challenge.

Vitamin D exerts endogenous control over T2 cell fate and immune plasticity.

Circulating Vitamin D (Vit-D) has emerged as a potent immune modulator in asthma, yet its direct impact on T2 cell regulation, the central effectors of allergic inflammation, remains unclear. Preliminary transcriptomic analysis of neonatal cord blood revealed that gestational Vit-D deficiency corresponds to elevated adaptive and innate immune responses, driven by T2 immunity and antimicrobial responses related to asthma inflammation. To elucidate cell-specific molecular mechanisms of Vit-D, we differentiated murine T2 cells under conditions mimicking Vit-D sufficiency and deficiency.

Distinct physiological, transcriptomic, and imaging characteristics of asthma-COPD overlap compared to asthma and COPD in smokers.

Background: The clinical and pathological features of asthma and chronic obstructive pulmonary disease (COPD) can converge in smokers and elderly individuals as asthma-COPD overlap (ACO). This overlap challenges the diagnosis and treatment of the distinct aetiologies underlying these conditions.

Methods: We analysed 2453 smokers (≥10 pack-years), aged 45-80 years, from the Genetic Epidemiology of COPD (COPDGene) Study, stratified as Control, Asthma, COPD, and ACO based on Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria.

The value of prospective metabolomic susceptibility endotypes: broad applicability for infectious diseases.

Background: As new infectious diseases (ID) emerge and others continue to mutate, there remains an imminent threat, especially for vulnerable individuals. Yet no generalizable framework exists to identify the at-risk group prior to infection. Metabolomics has the advantage of capturing the existing physiologic state, unobserved via current clinical measures.