A5003813203- RNA modifications and cancer
- Genomics and Phylogenetic Studies
- Antibiotic Resistance in Bacteria
- RNA Research and Splicing
- Single-cell and spatial transcriptomics
- Genetic Associations and Epidemiology
- Bacteriophages and microbial interactions
- Gut microbiota and health
- Epigenetics and DNA Methylation
- Helicobacter pylori-related gastroenterology studies
- Cancer Genomics and Diagnostics
- Congenital heart defects research
- Genomics and Chromatin Dynamics
- Adipose Tissue and Metabolism
- Pneumonia and Respiratory Infections
- interferon and immune responses
- Hemophilia Treatment and Research
- COVID-19 Clinical Research Studies
- Cancer-related molecular mechanisms research
- HIV Research and Treatment
- Cancer-related gene regulation
- Virus-based gene therapy research
- Enterobacteriaceae and Cronobacter Research
- RNA regulation and disease
- Blood Coagulation and Thrombosis Mechanisms
Wellcome Sanger Institute
2020-2025
New York Genome Center
2025
Australian Regenerative Medicine Institute
2018-2021
Monash University
2018-2021
The University of Melbourne
2018-2019
Klebsiella pneumoniae has emerged as an important cause of two distinct public health threats: multi-drug resistant (MDR) healthcare-associated infections and drug susceptible community-acquired invasive infections. These pathotypes are generally associated with subsets K. lineages or 'clones' that distinguished by the presence acquired resistance genes several key virulence loci. Genomic evolutionary analyses most notorious MDR community-associated ('hypervirulent') clones indicate...
Most genetic risk variants for neurological diseases are located in non-coding regulatory regions, where they may often act as expression quantitative trait loci (eQTLs), modulating gene and influencing disease susceptibility. However, eQTL studies bulk brain tissue or specific cell types lack the resolution to capture brain's cellular diversity. Single-nucleus RNA sequencing (snRNA-seq) offers high-resolution mapping of eQTLs across diverse types. Here, we performed a meta-analysis,...
Gene misexpression is the aberrant transcription of a gene in context where it usually inactive. Despite its known pathological consequences specific rare diseases, we have limited understanding wider prevalence and mechanisms humans. To address this, analyzed 4,568 whole-blood bulk RNA sequencing samples from INTERVAL study blood donors. We found that while individual events occur rarely, aggregate they were almost all third inactive protein-coding genes. Using 2,821 paired whole-genome...
Summary The biological mechanisms through which most non-protein-coding genetic variants affect disease risk are unknown. To investigate the gene-regulatory cascades that ensue from these variants, we mapped blood gene expression and splicing quantitative trait loci (QTLs) bulk RNA-sequencing in 4,732 participants, integrated data with protein, metabolite lipid QTLs same individuals. We identified cis -QTLs for of 17,233 genes 29,514 events (in 6,853 genes). Using colocalization analysis,...
Abstract Co-evolution between humans and the microbial communities colonizing them has resulted in an intimate assembly of thousands species mutualistically living on their body impacting multiple aspects host physiology health. Several studies examining whether human genetic variation can affect gut microbiota suggest a complex combination environmental factors. Here, we leverage single large-scale population-based cohort 5,959 genotyped individuals with matched shotgun metagenomes, dietary...
A strong focus of the post-genomic era is mining non-coding regulatory genome in order to unravel function elements that coordinate gene expression (Nat 489:57–74, 2012; Nat 507:462–70, 2014; 507:455–61, 518:317–30, 2015). Whole-genome approaches based on next-generation sequencing (NGS) have provided insight into genomic location throughout different cell types, organs and organisms. These technologies are now widespread commonly used laboratories from various fields research. This...
Linear plasmids are extrachromosomal DNA elements that have been found in a small number of bacterial species. To date, the only linear described family Enterobacteriaceae belong to Salmonella , first enterica Typhi. Here, we describe collection 12 isolates Klebsiella pneumoniae species complex which identified plasmids. Screening assembly graphs assembled from public read sets plasmid structures further 13 K . genomes. We used these 25 sequences query all genome assemblies National Center...
Given the large number of genes significantly associated with risk for neuropsychiatric disorders, a critical unanswered question is extent to which diverse mutations --sometimes impacting same gene-- will require tailored therapeutic strategies. Here we consider this in context rare disorder-associated copy variants (2p16.3) resulting heterozygous deletions
Abstract Two decades of Genome Wide Association Studies (GWAS) have yielded hundreds thousands robust genetic associations to human complex traits and diseases. Nevertheless, the dissection functional consequences variants lags behind, especially for non-coding (RNVs). Here we characterised a set rare, with large effects on haematological by integrating (i) massively parallel reporter assay (ii) CRISPR/Cas9 screen (iii) in vivo gene expression transcript relative abundance analysis whole...
Abstract Gene misexpression is the aberrant transcription of a gene in context where it usually inactive. Despite its known pathological consequences specific rare diseases, we have limited understanding wider prevalence and mechanisms humans. To address this, analyzed 4,568 whole blood bulk RNA sequencing samples from INTERVAL study donors. We found that while individual events occur rarely, aggregate they were almost all over half inactive genes. Using 2,821 paired genome samples,...
Severe COVID-19 is characterised by immunopathology and epithelial injury. Proteomic studies have identified circulating proteins that are biomarkers of severe COVID-19, but cannot distinguish correlation from causation. To address this, we performed Mendelian randomisation (MR) to identify mediate COVID-19. Using protein quantitative trait loci (pQTL) data the SCALLOP consortium, involving meta-analysis up 26,494 individuals, genome-wide association Host Genetics Initiative, MR for 157...
Abstract Understanding spatial gene expression and regulation is key to uncovering developmental physiological processes, during homeostasis disease. Numerous techniques exist gain information, but very few utilise intuitive true-to-life three-dimensional representations analyze visualize results. Here we combined transcriptomics with 3D modelling represent interrogate, transcriptome-wide, location in the mouse adult heart. Our study has unveiled specific subsets of genes that display...
Abstract Klebsiella pneumoniae ( Kp ) has emerged as an important cause of two distinct public health threats: multidrug resistant (MDR) healthcare-associated infections 1 and community-acquired invasive infections, particularly pyogenic liver abscess 2 . The majority MDR hospital outbreaks are caused by a subset clones with high prevalence acquired antimicrobial resistance (AMR) genes, while the ‘hypervirulent’ that rarely harbour AMR genes but have key virulence loci 3–5 Worryingly, last...
Klebsiella pneumoniae (Kp) is an infamous cause of multi-drug resistant (MDR) healthcare-associated infections and several MDR clones are globally distributed. A small number drug-susceptible have also become distributed, causing severe community-acquired infections. These ‘hypervirulent’ distinguished by expression highly serum-resistant K1/K2 capsules, plus high prevalence acquired virulence determinants. While hypervirulence drug resistance usually mutually exclusive, there now increasing...
Abstract Linear plasmids are extrachromosomal DNA that have been found in a small number of bacterial species. To date, the only linear described Enterobacteriaceae family belong to Salmonella, first Salmonella Typhi. Here, we describe collection 12 isolates Klebsiella pneumoniae species complex which identified plasmids. We used this search public sequence databases and discovered an additional 74 plasmid sequences variety Gene content analysis divided these into five distinct phylogroups,...