Adapting systems biology to address the complexity of human disease in the single-cell era.

Systems biology aims to achieve holistic insights into the molecular workings of cellular systems through iterative loops of measurement, analysis and perturbation. This framework has had remarkable success in unicellular model organisms, and recent experimental and computational advances - from single-cell and spatial profiling to CRISPR genome editing and machine learning - have raised the exciting possibility of leveraging such strategies to prevent, diagnose and treat human diseases. However, adapting systems-inspired approaches to dissect human disease complexity is challenging, given that discrepancies between the biological features of human tissues and the experimental models typically used to probe function (which we term 'translational distance') can confound insight.

Compromised Intestinal Barrier Resilience to Disruption in People with HIV.

People with HIV (PWH) experience chronic intestinal barrier dysfunction which contributes to chronic inflammation and its comorbidities. The mechanisms underlying this phenomenon remain unclear. We hypothesize that living with HIV compromises the intestinal barrier's resilience to injurious agents, increasing susceptibility to leakage upon exposure to disruptors.

Association of cytomegalovirus serostatus with ELOVL2 methylation: Implications for lipid metabolism, inflammation, DNA damage, and repair capacity in the MARK-AGE study population.

Cytomegalovirus (CMV) infection has been linked to accelerated biological aging, potentially increasing the risk of cardiovascular disease. DNA methylation of the gene Elongation Of Very Long Chain Fatty Acids-Like 2 (ELOVL2) is a molecular biomarker for aging, and its gene product is involved in polyunsaturated fatty acid synthesis, which impacts immune and inflammatory responses. This study, conducted in the MARK-AGE population, aimed to investigate the relationship between CMV infection and ELOVL2 methylation in adults aged 35-75, as well as the influence of CMV IgG levels on lipid metabolism, inflammation, DNA damage, and DNA repair.

Programs, origins and immunomodulatory functions of myeloid cells in glioma.

Gliomas are incurable malignancies notable for having an immunosuppressive microenvironment with abundant myeloid cells, the immunomodulatory phenotypes of which remain poorly defined. Here we systematically investigate these phenotypes by integrating single-cell RNA sequencing, chromatin accessibility, spatial transcriptomics and glioma organoid explant systems. We discovered four immunomodulatory expression programs: microglial inflammatory and scavenger immunosuppressive programs, which are both unique to primary brain tumours, and systemic inflammatory and complement immunosuppressive programs, which are also expressed by non-brain tumours.