Sean M. Grimmond
A5040120471- Cancer Genomics and Diagnostics
- Pancreatic and Hepatic Oncology Research
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- RNA and protein synthesis mechanisms
- Renal and related cancers
- RNA Research and Splicing
- Cancer, Hypoxia, and Metabolism
- CRISPR and Genetic Engineering
- Neuroendocrine Tumor Research Advances
- Angiogenesis and VEGF in Cancer
- Pluripotent Stem Cells Research
- Genomics and Phylogenetic Studies
- Cancer-related molecular mechanisms research
- Genomics and Chromatin Dynamics
- Renal cell carcinoma treatment
- Ovarian cancer diagnosis and treatment
- Genetic factors in colorectal cancer
- MicroRNA in disease regulation
- Cancer Cells and Metastasis
- Cancer Research and Treatments
- Genomics and Rare Diseases
- Lung Cancer Treatments and Mutations
- Molecular Biology Techniques and Applications
- Ubiquitin and proteasome pathways
The University of Melbourne
2016-2025
Victorian Comprehensive Cancer Centre
2017-2024
The University of Queensland
2010-2022
Westmead Institute for Medical Research
2018
Roche (Switzerland)
2018
AstraZeneca (Brazil)
2018
Queens University
2018
University of Glasgow
2013-2017
QIMR Berghofer Medical Research Institute
1994-2015
Royal Women's Hospital
2015
Only a small proportion of the mouse genome is transcribed into mature messenger RNA transcripts. There an international collaborative effort to identify all full-length mRNA transcripts from mouse, and ensure that each represented in physical collection clones. Here we report manual annotation 60,770 complementary DNA sequences. These are clustered 33,409 'transcriptional units', contributing 90.1% newly established transcriptome database. Of these transcriptional units, 4,258 new...
The transcriptional networks that regulate embryonic stem (ES) cell pluripotency and lineage specification are the subject of considerable attention. To date such studies have focused almost exclusively on protein-coding transcripts. However, recent transcriptome analyses show mammalian genome contains thousands long noncoding RNAs (ncRNAs), many which appear to be expressed in a developmentally regulated manner. functions these remain untested. identify ncRNAs involved ES biology, we used...
We evaluated 25 protocol variants of 14 independent computational methods for exon identification, transcript reconstruction and expression-level quantification from RNA-seq data. Our results show that most algorithms are able to identify discrete components with high success rates but assembly complete isoform structures poses a major challenge even when all constituent elements identified. Expression-level estimates also varied widely across methods, based on similar models. Consequently,...
Recent large-scale analyses of mainly full-length cDNA libraries generated from a variety mouse tissues indicated that almost half all representative cloned sequences did not contain an apparent protein-coding sequence, and were putatively derived non-protein-coding RNA (ncRNA) genes. However, many these clones singletons the majority unspliced, raising possibility they may be genomic DNA or unprocessed pre-mRNA contamination during library construction, alternatively represent nonspecific...
The Protein Interaction Network Analysis (PINA) platform is a comprehensive web resource, which includes database of unified protein–protein interaction data integrated from six manually curated public databases, and set built-in tools for network construction, filtering, analysis visualization. second version PINA enhances its utility studies protein interactions at level, by including multiple collections modules identified different clustering approaches the whole ('interactome') model...
Abstract Background Variants of microRNAs (miRNAs), called isomiRs, are commonly reported in deep-sequencing studies; however, the functional significance these variants remains controversial. Observational studies show that isomiR patterns non-random, hinting molecules could be regulated and therefore functional, although no conclusive biological role has been demonstrated for molecules. Results To assess relevance we have performed ultra-deep miRNA-seq on ten adult human tissues, created...
Abstract Background MicroRNAs are modifiers of gene expression, acting to reduce translation through either translational repression or mRNA cleavage. Recently, it has been shown that some microRNAs can act promote suppress cell transformation, with miR-17-92 described as the first oncogenic microRNA. The association encoded a surprisingly broad range cancers not only underlines clinical significance this locus, but also suggests may regulate fundamental biological processes, and for these...
Abstract As whole-genome sequencing for cancer genome analysis becomes a clinical tool, full understanding of the variables affecting output is required. Here using tumour-normal sample pairs from two different types cancer, chronic lymphocytic leukaemia and medulloblastoma, we conduct benchmarking exercise within context International Cancer Genome Consortium. We compare methods, pipelines validation methods. show that PCR-free methods increasing depth to ∼100 × shows benefits, as long...
Evolutionary change in gene expression is generally considered to be a major driver of phenotypic differences between species. We investigated innate immune diversification by analyzing interspecies the transcriptional responses primary human and mouse macrophages Toll-like receptor (TLR)–4 agonist lipopolysaccharide (LPS). By using custom platform permitting cross-species interrogation coupled with deep sequencing mRNA 5′ ends, we identified extensive divergence LPS-regulated orthologous...
Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large exome sequencing date have found recurrent loss-of-function mutations, oncogenic driving events been underrepresented. Here we use a combination whole-genome (WGS) single-nucleotide polymorphism-array profiling show that genomic catastrophes are frequent EAC, with almost third (32%, n=40/123)...
Personalized medicine strategies using genomic profiling are particularly pertinent for pancreas cancer. The Individualized Molecular Pancreatic Cancer Therapy (IMPaCT) trial was initially designed to exploit results from genome sequencing of pancreatic cancer under the auspices International Genome Consortium (ICGC) in Australia. Sequencing revealed small subsets patients with aberrations their tumor that could be targeted currently available therapies.
Abstract Heterogeneous subtypes of cancer-associated fibroblasts (CAFs) coexist within pancreatic cancer tissues and can both promote restrain disease progression. Here, we interrogate how cells harboring distinct alterations in p53 manipulate CAFs. We reveal the existence a p53-driven hierarchy, where with gain-of-function (GOF) mutant educate dominant population CAFs that establish pro-metastatic environment for GOF null alike. also demonstrate educated by may be reprogrammed either or...