Publications 

The Ramaciotti Centre supports research across the life sciences and was acknowledged as the provider of genomic data for or as an author on >260 peer reviewed papers in the period from July 2018 - June 2020.

Below are some selected publications from this list:

Publication

Genetic variation in PEAR1, cardiovascular outcomes and effects of aspirin in a healthy elderly population. Clinical Pharmacology and Therapeutics (Jun 2020) 
DOI: 10.1002/cpt.1959

SERVICE USED: Axiom Genotpying

BACKGROUND

The platelet endothelial aggregation receptor‐1 (PEAR1 ) rs12041331 variant has been identified as a genetic determinant of platelet aggregation in response to antiplatelet therapies, including aspirin. However, association with atherothrombotic cardiovascular events is less clear, with limited evidence from large trials. Here, we tested association of rs12041331 with cardiovascular events and aspirin use in a randomized trial population of healthy older individuals. We undertook post‐hoc analysis of N=13,547 participants of the ASPirin in Reducing Events in the Elderly (ASPREE) trial, median age 74 years. Participants had no previous diagnosis of atherothrombotic cardiovascular disease at enrolment, and were randomized to either 100 mg daily low‐dose aspirin or placebo for median 4.7 years follow‐up. We used Cox proportional hazard regression to model the relationship between rs12041331 and the ASPREE primary cardiovascular disease endpoint (CVD), and composites of major adverse cardiovascular events (MACE) and ischaemic stroke (STROKE); and bleeding events; major hemorrhage (MHEM) and intracranial bleeding (ICB). We performed whole‐population analysis using additive and dominant inheritance models, then stratified by treatment group. Interaction effects between genotypes and treatment group were examined. We observed no statistically significant association (P<0.05) in the population, or by treatment group, between rs12041331 and cardiovascular or bleeding events in either model. We also found no significant interaction effects between rs12041331‐A and treatment group, for CVD (P=0.65), MACE (P=0.32), STROKE (P=0.56), MHEM (P=0.59) or ICB (P=0.56). The genetic variant PEAR1 rs12041331 is not associated with cardiovascular events in response to low‐dose aspirin in a healthy elderly population.

 

Publication

Heat-evolved microalgal symbionts increase coral bleaching tolerance. Science Advances (May 2020) vol 6:20
DOI: 10.1126/sciadv.aba2498

SERVICE USED: Illumina NGS - whole genome sequencing

BACKGROUND

Coral reefs worldwide are suffering mass mortalities from marine heat waves. With the aim of enhancing coral bleaching tolerance, we evolved 10 clonal strains of a common coral microalgal endosymbiont at elevated temperatures (31°C) for 4 years in the laboratory. All 10 heat-evolved strains had expanded their thermal tolerance in vitro following laboratory evolution. After reintroduction into coral host larvae, 3 of the 10 heat-evolved endosymbionts also increased the holobionts’ bleaching tolerance. Although lower levels of secreted reactive oxygen species (ROS) accompanied thermal tolerance of the heat-evolved algae, reduced ROS secretion alone did not predict thermal tolerance in symbiosis. The more tolerant symbiosis exhibited additional higher constitutive expression of algal carbon fixation genes and coral heat tolerance genes. These findings demonstrate that coral stock with enhanced climate resilience can be developed through ex hospite laboratory evolution of their microalgal endosymbionts.

 

Publication

JMJD6 is a tumorigenic factor and therapeutic target in neuroblastoma. Nat Commun (Jul 2019) vol 10:3319
DOI: 
10.1038/s41467-019-11132-w

SERVICES USED: Illumina NGS ChIP Seq & Gene Expression Microarray

BACKGROUND Chromosome 17q21-ter is commonly gained in neuroblastoma, but it is unclear which gene in the region is important for tumorigenesis. The JMJD6 gene at 17q21-ter activates gene transcription. Here we show that JMJD6 forms protein complexes with N-Myc and BRD4, and is important for E2F2, N-Myc and c-Myc transcription. Knocking down JMJD6 reduces neuroblastoma cell proliferation and survival in vitro and tumor progression in mice, and high levels of JMJD6 expression in human neuroblastoma tissues independently predict poor patient prognosis. In addition, JMJD6 gene is associated with transcriptional super-enhancers. Combination therapy with the CDK7/super-enhancer inhibitor THZ1 and the histone deacetylase inhibitor panobinostat synergistically reduces JMJD6, E2F2, N-Myc, c-Myc expression, induces apoptosis in vitro and leads to neuroblastoma tumor regression in mice, which are significantly reversed by forced JMJD6 over-expression. Our findings therefore identify JMJD6 as a neuroblastoma tumorigenesis factor, and the combination therapy as a treatment strategy.

 

Publication

Specific Bacteria and Metabolites Associated with Response to Fecal Microbiota Transplantation in Patients with Ulcerative Colitis. Gastroenterology (Apr 2019) vol 156:1440-1454
DOI: 
10.1053/j.gastro.2018.12.001

SERVICE USED: 16S amplicon sequencing and shotgun metagenomic sequencing 

BACKGROUND Faecal microbiota transplantation (FMT) can induce remission in patients with ulcerative colitis (UC). In a randomized controlled trial of FMT in patients with active UC, the authors identified bacterial taxonomic and functional factors associated with response to therapy. These findings may be used in design of microbe-targeting therapies for ulcerative colitis

 

Publication

Adaption and conservation insights from the koala genome. Nature Genetics (Aug 2018) vol 50:1102-111
DOI: 
10.1038/s41588-018-0153-5

SERVICES USED: PacBio long-read service & Illumina NGS 

BACKGROUND

The koala, the only extant species of the marsupial family Phascolarctidae, is classified as ‘vulnerable’ due to habitat loss and widespread disease. We sequenced the koala genome, producing a complete and contiguous marsupial reference genome, including centromeres. We reveal that the koala’s ability to detoxify eucalypt foliage may be due to expansions within a cytochrome P450 gene family, and its ability to smell, taste and moderate ingestion of plant secondary metabolites may be due to expansions in the vomeronasal and taste receptors. We characterized novel lactation proteins that protect young in the pouch and annotated immune genes important for response to chlamydial disease. Historical demography showed a substantial population crash coincident with the decline of Australian megafauna, while contemporary populations had biogeographic boundaries and increased inbreeding in populations affected by historic translocations. We identified genetically diverse populations that require habitat corridors and instituting of translocation programs to aid the koala’s survival in the wild.

 

Publication

Draft genome assembly of the invasive cane toad, Rhinella marina. GigaScience (Aug 2018) vol 7:1-13
DOI: 10.1093/gigascience/giy095

SERVICES USED: PacBio long-read service & Illumina NGS 

BACKGROUND The cane toad (Rhinella marina formerly Bufo marinus) is a species native to Central and South America that has spread across many regions of the globe including Australia. Cane toads are known for their rapid adaptation and deleterious impacts on native fauna in invaded regions. However, despite an iconic status, there are major gaps in our understanding of cane toad genetics. The authors report a draft genome assembly for R. marina, the first of its kind for the Bufonidae family. The availability of the genome will help to close these gaps and accelerate cane toad research.