Panel sequencing of jSLE patients
Juvenile onset systemic lupus erythematosus (jSLE) affects 15 20% of lupus patients, but there is significant clinical heterogeneity between age and racial groups, as well as between individual patients. This study aimed to identify damaging gene mutations in SLE and SLE like disease presentations to distinguish between “genetic” SLE and other SLE patients. Using a hybrid capture approach, short read sequencing was performed on samples taken from 348 patients, targeting 23 genes associated with Mendelian forms of SLE/SLE like disease, as well as 40 additional genomic regions, comprising 59 genes and over 130 SLE associated risk sites. Damaging gene variants were identified in ~3.5% of patients and were associated with younger onset of disease and distinct clinical features. This work demonstrates that routine sequencing of SLE could allow for patient stratification, risk assessment and target directed treatment.
Full article: Charras , A., et al . 2022. Panel sequencing links rare, likely damaging gene variants with distinct clinical phenotypes and outcomes in juvenile onset SLE. Rheumatology.
Medical. Hybrid capture. Short read.
Assessing chromatin accessibility in hypoxic conditions using ATAC sequencing
Hypoxia can act as a signalling cue in physiological processes, such as development, but also in pathological conditions such as cancer. This study aimed to identify changes in chromatin accessibility when human cells are subjected to oxygen deprivation and reoxygenation with the Assay for Transposase Accessible Chromatin using sequencing (ATAC Seq). RNA sequencing was also used to measure changes in transcript levels associated with hypoxic conditions. The role of Hypoxia Inducible Factors (HIFs) was als o
examined via the use of a specific stabilise of HIF α and siRNA mediated depletion of HIF 1 β . This integrative analysis demonstrated that hypoxia induces specific changes to chromatin accessibility, which is reflected in changes to gene expression. Most of these changes were found to be HIF dependent and rapidly reversible upon reoxygenation.
Full article: Batie, M., et al . 2022. Regulation of chromatin accessibility by hypoxia and HIF . Biochemical Journal.
Cell biology. ATAC-seq. RNAseq. Short-read.
A decision tree for the treatment of pig slurry
The application of pig slurry to agricultural land introduces pathogens and antibiotic resistance genes (ARGs) to the environment. As there is an increasing drive towards creation of sustainable circular economies, this study aimed to identify slurry treatmen ts that could be carried out locally and that would minimise risk to human health and the environment, while also maximising nutrient conte nt. The effects of storage, composting and anaerobic digestion were compared by analysing the microbiome of the slurry via shotgun metagenomic sequencing. Each treatment method was found to have advantages and disadvantages depending on the parameter measured. Storage and composting were optimal for removal of human pathogens, while anaerobic digestion was better for removal of anti microbial resistance (AMR) genes and mobile genetic elements. The resulting data were used to develop a decision tree to determine the optimal treatment of slurry in different contexts.
Full article: Do, T. T., et al . 2022. Data based slurry treatment decision tree to minimise antibiotic resistance and pathogen transfer while maximising nutrient recycling. Environmental pollution.
Environment. Metagenomics. KEGG analysis. Short-read.
Responding to the COVID-19 pandemic
CGR staff were involved in several different consortia and research programmes providing sequencing and analysis capabilities in response to the COVID 19 pandemic. Included amongst these efforts were:
- Infection tracking for the Office for National Statistics
- Collaborating with 16 hospital diagnostic laboratories to sequence over 25,000 samples taken from primary healthcare settings across the North West of England
- Participation in the AGILE coronavirus clinical trial drug testing initiative to assess the impact of viral variants on drug efficacy
- Surveillance work for the COVID-19 Genomics UK (COG UK) consortium, including the Hospital Onset COVID 19 Infections study, CGR co director Professor Alistair Darby was also the deputy director of COG UK
- Providing sequencing capability for the Real-time Assessment of Community Transmission (REACT) study
- Assessing immune response, vaccine efficacy and reinfection as a partner in the SARS-CoV-2 Immunity and Reinfection Evaluation (SIREN) study
- Working with the UK Health Security Agency.
All data generated as part of these programmes were submitted to trusted research environments and made publicly available for real-time monitoring.
Websites:
Selected articles:
- Jackson, B.,et al . 2021. Generation and transmission of interlineage recombinants in the SARS CoV 2 pandemic. Cell.
COVID19.
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