Project description:We investigated differentially expressed sncRNAs in human sperm as candidate markers for evaluating sperm quality during IVF. We demonstrated that differentially expressed tsRNAs, rsRNAs and miRNAs are linked to sperm quality according to embryo quality, even though these sperm samples were all considered normal by the traditional semen-parameter assessment. Therefore, the sncRNAs, especially tsRNAs and rsRNAs, may be potential clinical biomarkers for the assessment of sperm quality in IVF.
Project description:Despite the widespread adoption of ChIP-seq there is still no consensus on quality assessment metrics. No single published metric can reliably discriminate the success or failure of an experiment, thus hampering objectivity and reproducibility of quality control. We introduce a new framework for ChIP-seq data quality assessment that overcomes the limitation of previous solutions. Our tool called "ChIC" incorporates a novel set of quality control metrics integrated into one single score summarizing the sample quality and a reference compendium with thousands of published ChIP-seq samples, for easier evaluation of new data. This test dataset contain an example of succesfull and non-succesfull ChIP-seq sample for mouse H3K27me3.
Project description:Chimeric antigen receptor-modified T cell (CAR-T) immunotherapy has revolutionized the treatment of blood cancers. Parsing the genetic underpinnings of T cell precursor quality and subsequent CAR-T efficacy is challenging. RNA-seq informs infused CAR-T state, but the nature of dynamic transcription during activation hinders identification of transiently or minimally expressed genes, such as transcription factors, and over-emphasizes effector and metabolism genes. We investigated whether analyses of transcriptionally repressive and permissive histone methylation marks reveal associations with CAR-T potential beyond what is seen by transcriptomic analysis. We assessed human CD8+ T cell naïve, central and effector memory subsets that form the substrate of CAR-T cell products, and CAR-T cells derived from these subsets. We extended these observations into the clinic, by examining CAR-T products from a clinical trial of lymphoma patients (NCT01865617). We report that histone marks provide a rich dataset for identification of genes not apparent by conventional transcriptomics. Histone marks improved identification of T cell subsets, CAR-T manufactured from these subsets, and CAR-T manufactured from central memory cells from healthy donors and patients. Using this discriminative approach, we controlled for clinical factors and identified a factor, KLF7, associated with CAR-T cell expansion in patients. Epigenomic methods are an orthogonal, robust and wide-reaching approach for the assessment of T cell immunotherapeutic quality.
Project description:Patients living with Human Immunodeficiency Virus (PLWH) develop accelerated liver fibrosis, but the exact mechanism remains unknown. Unlike gram-negative bacterial products, the impact of gram-positive microbial products in Human Immunodeficiency Virus 1 (HIV-1) associated liver inflammation and fibrosis remains poorly understood. In this study, we investigated the effect of lipoteichoic acid (LTA), a major gram-positive bacterial component, on HSCs in the context of HIV-1 infection. Our data revealed that HIV-1 infection sensitizes HSCs to LTA stimulation, leading to an amplified IL-8 response mediated through histone acetylation that may accelerate liver fibrosis progression in PLWH. As microbial translocation persists despite effective antiretroviral therapy, these findings underscore the need for targeted strategies to mitigate liver fibrosis in HIV-1 infected patients.
