A5013816044- Acute Lymphoblastic Leukemia research
- Acute Myeloid Leukemia Research
- RNA modifications and cancer
- Genomics and Phylogenetic Studies
- Cancer Genomics and Diagnostics
- Epigenetics and DNA Methylation
- Childhood Cancer Survivors' Quality of Life
- Chronic Myeloid Leukemia Treatments
- Gene expression and cancer classification
- Simulation Techniques and Applications
- Pancreatic and Hepatic Oncology Research
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Parallel Computing and Optimization Techniques
- Chronic Lymphocytic Leukemia Research
- Cancer-related molecular mechanisms research
- Eosinophilic Disorders and Syndromes
- Peptidase Inhibition and Analysis
- Molecular Biology Techniques and Applications
- Genomics and Rare Diseases
- Viral-associated cancers and disorders
The University of Melbourne
2020-2023
Peter MacCallum Cancer Centre
2020-2023
Murdoch Children's Research Institute
2017-2022
Royal Children's Hospital
2017-2019
Abstract Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, and implementation of risk-adapted therapy has been instrumental in dramatic improvements clinical outcomes. A key to therapies includes identification genomic features individual tumors, including chromosome number (for hyper- hypodiploidy) gene fusions, notably ETV6-RUNX1, TCF3-PBX1, BCR-ABL1 B-cell ALL (B-ALL). RNA-sequencing (RNA-seq) large cohorts expanded recurrent fusions recognized as drivers ALL,...
orn et al 6 (Lund, accession no.
Calling fusion genes from RNA-seq data is well established, but other transcriptional variants are difficult to detect using existing approaches. To identify all types of in transcriptomes we developed MINTIE, an integrated pipeline for data. We take a reference-free approach, combining de novo assembly transcripts with differential expression analysis up-regulated novel case sample. compare MINTIE eight approaches, detecting > 85% while no method able achieve this. posit that will be new...
Genomic profiling efforts have revealed a rich diversity of oncogenic fusion genes. While there are many methods for identifying genes from RNA-sequencing (RNA-seq) data, visualizing these transcripts and their supporting reads remains challenging. Clinker is bioinformatics tool written in Python, R, Bpipe that leverages the superTranscript method to visualize We demonstrate use obtain interpretable visualizations RNA-seq data lead calls. In addition, we explore multiple with novel...
Philadelphia-like (Ph-like) acute lymphoblastic leukemia (ALL) is a high-risk subtype of B-cell ALL characterized by gene expression profile resembling Philadelphia chromosome-positive (Ph+ ALL) in the absence BCR-ABL1. Tyrosine kinase-activating fusions, some involving ABL1, are recurrent drivers Ph-like and targetable with tyrosine kinase inhibitors (TKIs). We identified rare instance SFPQ-ABL1 child ALL. expressed cytokine-dependent cell lines was sufficient to transform cells these were...
Abstract We report two patients with leukaemia driven by the rare CNTRL‐FGFR1 fusion oncogene. This arises from a t(8;9)(p12;q33) translocation, and is driver of biphenotypic in children. used RNA sequencing to novel features expressed , including alternative splicing. From this knowledge, we designed tested Droplet Digital PCR assay that detects expression approximately one cell 100 000 using breakpoint‐specific primers probes. also utilised cell‐line models show effective tyrosine kinase...
Abstract Genomic rearrangements can modify gene function by altering transcript sequences, and have been shown to be drivers in both cancer rare diseases. Although there are now many methods detect structural variants from Whole Genome Sequencing (WGS), RNA sequencing (RNA-seq) remains under-utilised as a technology for the detection of variants. Calling fusion genes RNA-seq data is well established, but other transcriptional such fusions with novel sequence, tandem duplications, large...
T-cell acute lymphoblastic leukemia (T-ALL) is a rare and aggressive hematologic malignancy affecting both children adults. 1,2 T-ALL subtype identification an emerging area of active research; as recently 2016, the World Health Organization suggested only 1 provisional distinct classification: early precursor (ETP). 3wever, recent revisions by International Consensus Classification in 2022 further subclassified ETP based on BCL11B deregulation while introducing 8 classifications for non-ETP...
Abstract B-cell acute lymphoblastic leukemia (B-ALL) is the most common childhood cancer. Subtypes within B-ALL are distinguished by characteristic structural variants and mutations, which in some instances strongly correlate with responses to treatment. The World Health Organisation (WHO) recognises seven distinct classifications, or subtypes , as of 2016. However, recent studies have demonstrated that can be segmented into 23 based on a combination genomic features gene expression...
Visualisation of the transcriptome relative to a reference genome is fraught with sparsity. This due RNA sequencing (RNA-Seq) reads being predominantly mapped exons that account for just under 3% human genome. Recently, we have used exon-only references, superTranscripts, improve visualisation aligned RNA-Seq data through omission supposedly unexpressed regions such as introns. However, variation within these can lead novel splicing events may drive pathogenic phenotype. In cases, loss...
ABSTRACT Genomic profiling efforts have revealed a rich diversity of oncogenic fusion genes, and many are emerging as important therapeutic targets. While there ways to identify genes from RNA-seq data, visualising these transcripts their supporting reads remains challenging. Clinker is bioinformatics tool written in Python, R Bpipe, that leverages the superTranscript method visualise genes. We demonstrate use obtain interpretable visualisations data lead calls. In addition, we explore...
Abstract T-cell acute lymphoblastic leukaemia (T-ALL) is an aggressive and heterogenous haematological malignancy affecting both children adults. T-ALL subtype identification emerging area of active research, with several recent studies proposing potential subtypes based on transcriptomic genomic analyses. Here we present TALLSorts, a machine-learning bioinformatic tool which classifies samples by using bulk RNA sequencing (RNA-seq) data. Trained four international cohorts totalling 264...