Clarke, P. | Search bioRxiv

bioRxiv2018

The plasma biomarker soluble SIGLEC-1 is associated with the type I interferon transcriptional signature, ethnic background and renal disease in systemic lupus erythematosus

The molecular heterogeneity of autoimmune and inflammatory diseases has been one of the main obstacles to the development of safe and specific therapeutic options. Here we have evaluated the diagnostic and clinical value of a robust, inexpensive, immunoassay detecting the circulating soluble form of the monocyte-specific surface receptor sialic acid binding Ig-like lectin 1 (sSIGLEC-1).\n\nWe developed an immunoassay to measure sSIGLEC-1 in small volumes of plasma/serum from systemic lupus erythematosus (SLE) patients and healthy donors. Plasma concentrations of sSIGLEC-1 strongly correlated with expression of SIGLEC-1 on the surface of blood monocytes and with type I interferon (IFN)-regulated gene (IRG) expression in SLE patients. In addition, we identified marked ancestry-related differences in sSIGLEC-1 concentrations in SLE patients, with patients of non-European ancestry showing higher levels compared to patients of European ancestry. Higher sSIGLEC-1 concentrations were associated with lower serum complement component 3 and increased frequency of renal complications in European patients, but not with the SLEDAI clinical score.\n\nOur sSIGLEC-1 immunoassay provides a specific and easily-assayed marker for monocyte-macrophage activation, and interferonopathy in SLE and other diseases. Further studies can extend its clinical associations and its potential use to stratify patients and as a secondary endpoint in trials.

immunology↗

bioRxiv2017

Rapid MinION metagenomic profiling of the preterm infant gut microbiota to aid in pathogen diagnostics

The Oxford Nanopore MinION sequencing platform offers near real time analysis of DNA reads as they are generated, which makes the device attractive for in-field or clinical deployment, e.g. rapid diagnostics. We used the MinION platform for shotgun metagenomic sequencing and analysis of gut-associated microbial communities; firstly, we used a 20-species human microbiota mock community to demonstrate how Nanopore metagenomic sequence data can be reliably and rapidly classified. Secondly, we profiled faecal microbiomes from preterm infants at increased risk of necrotising enterocolitis and sepsis. In single patient time course, we captured the diversity of the immature gut microbiota and observed how its complexity changes over time in response to interventions, i.e. probiotic, antibiotics and episodes of suspected sepsis. Finally, we performed real-time runs from sample to analysis using faecal samples of critically ill infants and of healthy infants receiving probiotic supplementation. Real-time analysis was facilitated by our new NanoOK RT software package which analysed sequences as they were generated. We reliably identified potentially pathogenic taxa (i.e. Klebsiella pneumoniae and Enterobacter cloacae) and their corresponding antimicrobial resistance (AMR) gene profiles within as little as one hour of sequencing. Antibiotic treatment decisions may be rapidly modified in response to these AMR profiles, which we validated using pathogen isolation, whole genome sequencing and antibiotic susceptibility testing. Our results demonstrate that our pipeline can process clinical samples to a rich dataset able to inform tailored patient antimicrobial treatment in less than 5 hours.

genomics↗