Single-cell genomics-based immune and disease monitoring in blood malignancies.

Achieving long-term disease control using therapeutic immunomodulation is a long-standing concept with a strong tradition in blood malignancies. Besides allogeneic hematopoietic stem cell transplantation that continues to provide potentially curative treatment for otherwise challenging diagnoses, recent years have seen impressive progress in immunotherapies for leukemias and lymphomas with immune checkpoint blockade, bispecific monoclonal antibodies, and CAR T cell therapies. Despite their success, non-response, relapse, and immune toxicities remain frequent, thus prioritizing the elucidation of the underlying mechanisms and identifying predictive biomarkers. The increasing availability of single-cell genomic tools now provides a system's immunology view to resolve the molecular and cellular mechanisms of immunotherapies at unprecedented resolution. Here, we review recent studies that leverage these technological advancements for tracking immune responses, the emergence of immune resistance, and toxicities. As single-cell immune monitoring tools evolve and become more accessible, we expect their wide adoption for routine clinical applications to catalyze more precise therapeutic steering of personal immune responses.

Cardiovascular disease biomarkers derived from circulating cell-free DNA methylation.

Acute coronary syndrome (ACS) remains a major cause of worldwide mortality. The syndrome occurs when blood flow to the heart muscle is decreased or blocked, causing muscle tissues to die or malfunction. There are three main types of ACS: Non-ST-elevation myocardial infarction, ST-elevation myocardial infarction, and unstable angina. The treatment depends on the type of ACS, and this is decided by a combination of clinical findings, such as electrocardiogram and plasma biomarkers. Circulating cell-free DNA (ccfDNA) is proposed as an additional marker for ACS since the damaged tissues can release DNA to the bloodstream. We used ccfDNA methylation profiles for differentiating between the ACS types and provided computational tools to repeat similar analysis for other diseases. We leveraged cell type specificity of DNA methylation to deconvolute the ccfDNA cell types of origin and to find methylation-based biomarkers that stratify patients. We identified hundreds of methylation markers associated with ACS types and validated them in an independent cohort. Many such markers were associated with genes involved in cardiovascular conditions and inflammation. ccfDNA methylation showed promise as a non-invasive diagnostic for acute coronary events. These methods are not limited to acute events, and may be used for chronic cardiovascular diseases as well.