Richard Varhol
A5066311215- RNA modifications and cancer
- Neuroblastoma Research and Treatments
- Cancer Genomics and Diagnostics
- RNA Research and Splicing
- Primary Care and Health Outcomes
- Genomics and Chromatin Dynamics
- Gene expression and cancer classification
- Chromatin Remodeling and Cancer
- Molecular Biology Techniques and Applications
- Cancer, Hypoxia, and Metabolism
- RNA and protein synthesis mechanisms
- Ovarian cancer diagnosis and treatment
- Ethics in Clinical Research
- Genomic variations and chromosomal abnormalities
- Bioinformatics and Genomic Networks
- Health disparities and outcomes
- Cancer-related gene regulation
- Healthcare Systems and Technology
- Clinical practice guidelines implementation
- Epigenetics and DNA Methylation
- Endometrial and Cervical Cancer Treatments
- Machine Learning in Bioinformatics
- Cancer-related molecular mechanisms research
- Global Health Workforce Issues
- Genomics and Phylogenetic Studies
Curtin University
2014-2025
BC Cancer Agency
2003-2023
CRC for Spatial information
2018
Government of Western Australia Department of Health
2015-2017
University of British Columbia
2010-2013
Canada's Michael Smith Genome Sciences Centre
2005-2013
Children's Cancer Institute Australia
2010
Sydney Children's Hospital
2010
Institute of Molecular Biology and Biophysics
2010
University of Toronto
2010
We analysed primary breast cancers by genomic DNA copy number arrays, methylation, exome sequencing, messenger RNA microRNA sequencing and reverse-phase protein arrays. Our ability to integrate information across platforms provided key insights into previously defined gene expression subtypes demonstrated the existence of four main cancer classes when combining data from five platforms, each which shows significant molecular heterogeneity. Somatic mutations in only three genes (TP53, PIK3CA...
We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array- sequencing-based technologies. Uterine serous tumours ∼25% high-grade endometrioid had extensive copy number alterations, few DNA methylation changes, low oestrogen receptor/progesterone receptor levels, frequent TP53 mutations. Most alterations or mutations, but mutations in PTEN, CTNNB1, PIK3CA, ARID1A KRAS novel the SWI/SNF chromatin remodelling complex gene ARID5B....
Many mutations that contribute to the pathogenesis of acute myeloid leukemia (AML) are undefined. The relationships between patterns and epigenetic phenotypes not yet clear. We analyzed genomes 200 clinically annotated adult cases de novo AML, using either whole-genome sequencing (50 cases) or whole-exome (150 cases), along with RNA microRNA DNA-methylation analysis. AML have fewer than most other cancers, an average only 13 found in genes. Of these, 5 genes recurrently mutated AML. A total...
Next-generation sequencing approaches have been used to investigate the genomes and transcriptomes of an oestrogen-receptor-α-positive metastatic lobular breast cancer from a patient — rather than cell line or xenograft over 9-year period between diagnosis primary tumour appearance metastasis. Comparison somatic non-synonymous coding mutations in metastasis same combined analysis genome transcriptome data provided insights into mutational evolution that can occur with disease progression....
Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique...
Granulosa-cell tumors (GCTs) are the most common type of malignant ovarian sex cord-stromal tumor (SCST). The pathogenesis these is unknown. Moreover, their histopathological diagnosis can be challenging, and there no curative treatment beyond surgery.We analyzed four adult-type GCTs using whole-transcriptome paired-end RNA sequencing. We identified putative GCT-specific mutations that were present in at least three samples but absent from transcriptomes 11 epithelial tumors, published human...
An outbreak of tuberculosis occurred over a 3-year period in medium-size community British Columbia, Canada. The results mycobacterial interspersed repetitive unit–variable-number tandem-repeat (MIRU-VNTR) genotyping suggested the was clonal. Traditional contact tracing did not identify source. We used whole-genome sequencing and social-network analysis an effort to describe dynamics at higher resolution.
Sequence-based methods for transcriptome characterization have typically relied on generation of either serial analysis gene expression tags or expressed sequence tags. Although such approaches the potential to enumerate transcripts by counting derived from them, they do not robustly survey majority along their entire length. Here we show that massively parallel sequencing randomly primed cDNAs, using a next-generation sequencing-by-synthesis technology, offers generate relative measures...
Whole transcriptome shotgun sequencing data from non-normalized samples offer unique opportunities to study the metabolic states of organisms. One can deduce gene expression levels using sequence coverage as a surrogate, identify coding changes or discover novel isoforms transcripts. Especially for discovery events, de novo assembly transcriptomes is desirable.Transcriptome tumor tissue patient with follicular lymphoma was sequenced 36 base pair (bp) single- and paired-end reads on Illumina...
Oligodendroglioma is characterized by unique clinical, pathological, and genetic features. Recurrent losses of chromosomes 1p 19q are strongly associated with this brain cancer but knowledge the identity function genes affected these alterations limited. We performed exome sequencing on a discovery set 16 oligodendrogliomas 1p/19q co-deletion to identify new molecular features at base-pair resolution. As anticipated, there was high rate IDH mutations: all cases had mutations in either IDH1...
Abstract Summary: Next-generation sequencing can provide insight into protein–DNA association events on a genome-wide scale, and is being applied in an increasing number of applications genomics meta-genomics research. However, few software are available for interpreting these experiments. We present here efficient application use with chromatin-immunoprecipitation (ChIP-Seq) experimental data that includes novel functionality identifying areas gene enrichment transcription factor binding...
Adenocarcinomas of the tongue are rare and represent minority (20 to 25%) salivary gland tumors affecting tongue. We investigated utility massively parallel sequencing characterize an adenocarcinoma tongue, before after treatment. In pre-treatment tumor we identified 7,629 genes within regions copy number gain. There were 1,078 that exhibited increased expression relative blood unrelated four contained somatic protein-coding mutations. Our analysis suggested cells driven by RET oncogene....
Foxa2 (HNF3 beta) is a one of three, closely related transcription factors that are critical to the development and function mouse liver. We have used chromatin immunoprecipitation massively parallel Illumina 1G sequencing (ChIP-Seq) create genome-wide profile in vivo Foxa2-binding sites adult More than 65% approximately 11.5 k genomic associated with binding, mapped extended gene regions annotated genes, while more 30% intragenic were located within first introns. 20.5% all further 50 kb...
We analyzed 8.55 million LongSAGE tags generated from 72 libraries. Each library was prepared a different mouse tissue. Analysis of the data revealed extensive overlap with existing gene sets and evidence for existence ≈24,000 previously undescribed genomic loci. The visual cortex, pancreas, mammary gland, preimplantation embryo, placenta contain largest number differentially expressed transcripts, 25% which are
The Pleiades Promoter Project integrates genomewide bioinformatics with large-scale knockin mouse production and histological examination of expression patterns to develop MiniPromoters related tools designed study treat the brain by directed gene expression. Genes interest are subjected bioinformatic analysis delineate candidate regulatory regions, which then incorporated into a panel compact human drive regions cell types interest. Using single-copy, homologous-recombination “knockins” in...
Parathyroid carcinoma is a rare endocrine malignancy with an estimated incidence of less than 1 per million population. Excessive secretion parathyroid hormone, extremely high serum calcium level, and the deleterious effects hypercalcaemia are clinical manifestations disease. Up to 60% patients develop multiple disease recurrences although long-term survival possible palliative surgery, permanent remission rarely achieved. Molecular drivers sporadic have remained largely unknown. Previous...
Abstract Background Rural provider-to-provider telehealth is growing globally. It used to both facilitate equitable access specialist healthcare services for those living in rural and remote areas provide support place-based providers. There limited research on the implementation of these services, especially an emergency or inpatient hospital setting. The Western Australia Country Health Service (WACHS) Command Centre one such example. First implemented 2012, a geographical area covering...
Thapsigargin is a high affinity inhibitor of sarco- and endoplasmic reticulum (SERCA) type ATPases. We have used kinetics to determine the dissociation constant thapsigargin-sarcoplasmic Ca2+-ATPase interaction in absence presence non-ionic detergent. The observed "off" rate was measured as 0.0052 s-1 at 26°C by inhibition ATPase activity following transfer from an inactivated thapsigargin-ATPase complex native ATPase. Inactive produced cross-linking active site with glutaraldehyde....
Abstract Purpose: Neuroblastoma (NB) is an aggressive tumor of the developing peripheral nervous system that remains difficult to cure in advanced stages. The poor prognosis for high-risk NB patients associated with common disease recurrences fail respond available therapies. tumor-initiating cells (TICs), isolated from metastases and primary tumors, may escape treatment contribute relapse. New therapies target TICs therefore prevent or treat recurrences. Experimental Design: We undertook a...