A5062246521- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Genomics and Phylogenetic Studies
- Cancer Genomics and Diagnostics
- Genomics and Chromatin Dynamics
- Biomedical Text Mining and Ontologies
- Pluripotent Stem Cells Research
- Gene expression and cancer classification
- interferon and immune responses
- Bioinformatics and Genomic Networks
- Chromosomal and Genetic Variations
- Muscle Physiology and Disorders
- Single-cell and spatial transcriptomics
- Genetic Neurodegenerative Diseases
- Molecular Biology Techniques and Applications
- Renal and related cancers
- Epigenetics and DNA Methylation
- Fungal and yeast genetics research
- CRISPR and Genetic Engineering
- Glioma Diagnosis and Treatment
- Genetics, Aging, and Longevity in Model Organisms
- Scientific Computing and Data Management
- Cancer-related gene regulation
- Developmental Biology and Gene Regulation
Ottawa Hospital Research Institute
2012-2024
Ottawa Hospital
2012-2024
University of Ottawa
2005-2021
Ontario Genomics
2005-2007
Health Canada
2007
In spite of extensive research on the effect mutation and selection codon usage, a general model usage bias due to mutational has been lacking. Because most amino acids allow synonymous GC content changing substitutions in third position, overall genome or genomic region is highly correlated with GC3, measure position content. For individual as well, G/C ending codons generally increases increasing decreases AT bias. Arginine leucine, that GC-changing first positions, have which may be...
Abstract Mutations in proteins like FUS which cause Amyotrophic Lateral Sclerosis (ALS) result the aberrant formation of stress granules while ALS-linked mutations other impede elimination granules. Repeat expansions C9ORF72, major ALS, reduce C9ORF72 levels but how this impacts is uncertain. Here, we demonstrate that associates with autophagy receptor p62 and controls by autophagy. This requires to associate via Tudor protein SMN proteins, including FUS, are symmetrically methylated on...
Abstract Background Little is known about the genes that drive embryonic stem cell differentiation. However, such knowledge necessary if we are to exploit therapeutic potential of cells. To uncover genetic determinants mouse (mESC) differentiation, have generated and analyzed 11-point time-series DNA microarray data for three biologically equivalent but genetically distinct mESC lines (R1, J1, V6.5) undergoing undirected differentiation into embryoid bodies (EBs) over a period two weeks....
A growing number of solved protein structures display an elongated structural domain, denoted here as alpha-rod, composed stacked pairs anti-parallel alpha-helices. Alpha-rods are flexible and expose a large surface, which makes them suitable for interaction. Although most likely originating by tandem duplication two-helix unit, their detection using sequence similarity between repeats is poor. Here, we show that alpha-rod can be detected neural network. The network detects more than...
Polycomb repressive complex 2 (PRC2) accessory proteins play substoichiometric, tissue-specific roles to recruit PRC2 specific genomic loci or increase enzymatic activity, while core are required for stability and global levels of trimethylation histone 3 at lysine 27 (H3K27me3). Here, we demonstrate a role the classical protein Mtf2/Pcl2 in hematopoietic system that is more akin protein. Mtf2-/- erythroid progenitors markedly decreased loss H3K27me3 promoter-proximal regions. The resulting...
Summary Ideally, disease modeling using patient‐derived induced pluripotent stem cells ( iPSC s) enables analysis of initiation and progression. This requires any pathological features the patient used for reprogramming to be eliminated during generation. Hutchinson–Gilford progeria syndrome HGPS ) is a segmental premature aging disorder caused by accumulation truncated form Lamin A known as Progerin within nuclear lamina. Cellular hallmarks include blebbing, loss peripheral heterochromatin,...
Abstract OTX2 is a potent oncogene that promotes tumor growth in Group 3 medulloblastoma. However, the mechanisms by which represses neural differentiation are not well characterized. Here, we perform extensive multiomic analyses to identify an regulatory network controls medulloblastoma cell fate. silencing modulates repressive chromatin landscape, decreases levels of PRC2 complex genes and increases expression neurodevelopmental transcription factors including PAX3 PAX6 . Expression...
Abstract Motivation: Reliable estimation of the mean fragment length for next-generation short-read sequencing data is an important step in analysis pipelines, most notably because its impact on accuracy enriched regions identified by peak-calling algorithms. Although many algorithms include a fragment-length subroutine, problem has not been adequately solved, as demonstrated variability estimates returned different Results: In this article, we investigate use strand cross-correlation to...
Alpha-solenoids are flexible protein structural domains formed by ensembles of alpha-helical repeats (Armadillo and HEAT among others). While homology can be used to detect many these repeats, some alpha-solenoids have very little sequence proteins known structure we expect that remain undetected. We previously developed a method for detection based on neural network trained dataset structures. Here improved the algorithm updated training using recently solved structures alpha-solenoids....
Unraveling transcriptional regulatory networks is a central problem in molecular biology and, this quest, chromatin immunoprecipitation and sequencing (ChIP-seq) technology has given us the unprecedented ability to identify sites of protein-DNA binding histone modification genome wide. However, multiple systemic procedural biases hinder harnessing full potential technology. Previous studies have addressed problem, but thorough characterization different, interacting on ChIP-seq signals still...
Medulloblastoma ( MB ) is the most common malignant primary pediatric brain cancer. Among aggressive subtypes, Group 3 and 4 originate from stem/progenitor cells, frequently metastasize, often display worst prognosis, yet we know least about molecular mechanisms driving their progression. Here, show that transcription factor orthodenticle homeobox 2 OTX 2) promotes self‐renewal while inhibiting differentiation in vitro increases tumor initiation cells vivo . To determine how contributes to...
Currently one of the largest online repositories for human and mouse stem cell gene expression data, StemBase was first designed as a simple web-interface to DNA microarray data generated by Canadian Stem Cell Network facilitate discovery functions relevant control differentiation. Since its creation, has grown in both size scope into system with analysis tools that examine either whole database at once, or slices based on tissue type, type interest. As September 1, 2008, contains...
Abstract Background Treating cancer depends in part on identifying the mutations driving each patient’s disease. Many clinical laboratories are adopting high-throughput sequencing for assaying patients’ tumours, applying targeted panels to formalin-fixed paraffin-embedded tumour tissues detect clinically-relevant mutations. While there have been some benchmarking and best practices studies of this scenario, much variant calling work focuses whole-genome or whole-exome studies, with fresh...
Muscle-specific transcription factor MyoD orchestrates the myogenic gene expression program by binding to short DNA motifs called E-boxes within cis-regulatory elements (CREs). Genome-wide analyses of cistrome chromatin immnunoprecipitation sequencing shows that MyoD-bound CREs contain multiple various sequences. However, how E-box numbers, sequences and their spatial arrangement collectively regulate affinity transcriptional activity remain largely unknown. Here, an integrative analysis...
Background: Next-generation sequencing (NGS) of tumor genomes has changed and improved cancer treatment over the past few decades. It can inform clinicians on optimal therapeutic approach in many solid hematologic cancers, including non-small lung (NSCLC). Our study aimed to determine costs NGS assays for NSCLC diagnostics. Methods: We performed a micro-costing four (Trusight Tumor 170 Kit (Illumina), Oncomine Focus (Thermo Fisher), QIAseq Targeted DNA Custom Panel QIASeq RNAscan (Qiagen),...
The origin of new functions is fundamental in understanding evolution, and three processes known as adaptation, preadaptation, exaptation have been proposed possible evolutionary pathways leading to the functions. Here we examine an acid resistance mechanism mammalian gastric pathogen Helicobacter pylori, with reference these pathways. involved that H. when exposed acidic environment stomach, restricts acute proton entry across its membrane by increased usage positively charged amino acids...
SNP microarrays are designed to genotype Single Nucleotide Polymorphisms (SNPs). These report hybridization of DNA fragments and therefore can be used for the purpose detecting genomic fragments.Here, we demonstrate that a microarray effectively in this way perform chromatin immunoprecipitation (ChIP) on chip as an alternative tiling microarrays. We illustrate novel application by mapping whole genome histone H4 hyperacetylation human myoblasts myotubes. detect clusters hyperacetylated H4,...