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Identifying SETBP1 haploinsufficiency molecular pathways to improve patient diagnosis using induced pluripotent stem cells and neural disease modelling

SETBP1 Haploinsufficiency Disorder (SETBD) is characterised by mild to moderate intellectual disability, speech and language impairment, mild motor developmental delay, behavioural issues, hypotonia, mild facial dysmorphisms, and vision impairment. Despite a clear link between SETBP1 mutations and neurodevelopmental disorders the precise role of SETBP1 in neural development remains elusive.

Immune checkpoint therapy responders display early clonal expansion of tumor infiltrating lymphocytes

Immune checkpoint therapy (ICT) causes durable tumour responses in a subgroup of patients, but it is not well known how T cell receptor beta (TCRβ) repertoire dynamics contribute to the therapeutic response. 

Metagenomic Characterisation of the Gut Microbiome and Effect of Complementary Feeding on Bifidobacterium spp. in Australian Infants

Complementary feeding induces dramatic ecological shifts in the infant gut microbiota toward more diverse compositions and functional metabolic capacities, with potential implications for immune and metabolic health. The aim of this study was to examine whether the age at which solid foods are introduced differentially affects the microbiota in predominantly breastfed infants compared with predominantly formula-fed infants. 

CRISPR-Cas9-generated PTCHD1 2489T>G stem cells recapitulate patient phenotype when undergoing neural induction

An estimated 3.5%-5.9% of the global population live with rare diseases, and approximately 80% of these diseases have a genetic cause. Rare genetic diseases are difficult to diagnose, with some affected individuals experiencing diagnostic delays of 5-30 years. Next-generation sequencing has improved clinical diagnostic rates to 33%-48%. In a majority of cases, novel variants potentially causing the disease are discovered. 

Indigenous Australian genomes show deep structure and rich novel variation

The Indigenous peoples of Australia have a rich linguistic and cultural history. How this relates to genetic diversity remains largely unknown because of their limited engagement with genomic studies. Here we analyse the genomes of 159 individuals from four remote Indigenous communities, including people who speak a language (Tiwi) not from the most widespread family (Pama-Nyungan). This large collection of Indigenous Australian genomes was made possible by careful community engagement and consultation.

Trends in prenatal diagnosis of congenital anomalies in Western Australia between 1980 and 2020: A population-based study

Advances in screening and diagnostics have changed the way in which we identify and diagnose congenital anomalies.

SAMStat 2: quality control for next generation sequencing data

SAMStat is an efficient program to extract quality control metrics from fastq and SAM/BAM files. A distinguishing feature is that it displays sequence composition, base quality composition and mapping error profiles split by mapping quality. This allows users to rapidly identify reasons for poor mapping including the presence of untrimmed adapters or poor sequencing quality at individual read positions.

CD4+ T cells drive an inflammatory, TNF-α/IFN-rich tumor microenvironment responsive to chemotherapy

While chemotherapy remains the first-line treatment for many cancers, it is still unclear what distinguishes responders from non-responders. Here, we characterize the chemotherapy-responsive tumor microenvironment in mice, using RNA sequencing on tumors before and after cyclophosphamide, and compare the gene expression profiles of responders with progressors.

Association between craniofacial anomalies, intellectual disability and autism spectrum disorder: Western Australian population-based study

Accurate knowledge of the relationship between craniofacial anomalies (CFA), intellectual disability (ID) and autism spectrum disorder (ASD) is essential to improve services and outcomes. The aim is to describe the association between CFA, ID and ASD using linked population data.