Robert A. Holt
A5065733774- Cancer Genomics and Diagnostics
- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- Genomics and Phylogenetic Studies
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Occupational and environmental lung diseases
- Molecular Biology Techniques and Applications
- RNA modifications and cancer
- Medical Imaging and Pathology Studies
- Chromosomal and Genetic Variations
- T-cell and B-cell Immunology
- Genetic factors in colorectal cancer
- Pancreatic and Hepatic Oncology Research
- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- Enzyme Catalysis and Immobilization
- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Cancer-related molecular mechanisms research
- Gut microbiota and health
- Virus-based gene therapy research
- Genomic variations and chromosomal abnormalities
- Microbial Metabolic Engineering and Bioproduction
- Bacteriophages and microbial interactions
University of British Columbia
2015-2024
Canada's Michael Smith Genome Sciences Centre
2015-2024
Simon Fraser University
2015-2024
Amgen (United States)
2024
Horizon Therapeutics (United States)
2020-2024
Occupational Cancer Research Centre
2023
University College London
2023
University of Michigan
2023
Vancouver Coastal Health Research Institute
2023
Genome British Columbia
2006-2022
A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion human genome was generated by whole-genome shotgun sequencing method. The 14.8-billion bp DNA over 9 months from 27,271,853 high-quality reads (5.11-fold coverage genome) both ends plasmid clones made five individuals. Two assembly strategies—a and a regional chromosome assembly—were used, each combining data Celera publicly funded effort. public were shredded into 550-bp segments to create 2.9-fold those regions...
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...
The fly Drosophila melanogaster is one of the most intensively studied organisms in biology and serves as a model system for investigation many developmental cellular processes common to higher eukaryotes, including humans. We have determined nucleotide sequence nearly all ∼120-megabase euchromatic portion genome using whole-genome shotgun sequencing strategy supported by extensive clone-based high-quality bacterial artificial chromosome physical map. Efforts are under way close remaining...
Gastric cancer is a leading cause of deaths, but analysis its molecular and clinical characteristics has been complicated by histological aetiological heterogeneity. Here we describe comprehensive evaluation 295 primary gastric adenocarcinomas as part The Cancer Genome Atlas (TCGA) project. We propose classification dividing into four subtypes: tumours positive for Epstein–Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, amplification JAK2, CD274 (also...
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...
We performed an extensive immunogenomic analysis of more than 10,000 tumors comprising 33 diverse cancer types by utilizing data compiled TCGA. Across types, we identified six immune subtypes—wound healing, IFN-γ dominant, inflammatory, lymphocyte depleted, immunologically quiet, and TGF-β dominant—characterized differences in macrophage or signatures, Th1:Th2 cell ratio, extent intratumoral heterogeneity, aneuploidy, neoantigen load, overall proliferation, expression immunomodulatory genes,...
We report the draft genome of black cottonwood tree, Populus trichocarpa . Integration shotgun sequence assembly with genetic mapping enabled chromosome-scale reconstruction genome. More than 45,000 putative protein-coding genes were identified. Analysis assembled revealed a whole-genome duplication event; about 8000 pairs duplicated from that event survived in A second, older is indistinguishably coincident divergence and Arabidopsis lineages. Nucleotide substitution, tandem gene...
The Cancer Genome Atlas profiled 279 head and neck squamous cell carcinomas (HNSCCs) to provide a comprehensive landscape of somatic genomic alterations. Here we show that human-papillomavirus-associated tumours are dominated by helical domain mutations the oncogene PIK3CA, novel alterations involving loss TRAF3, amplification cycle gene E2F1. Smoking-related HNSCCs demonstrate near universal loss-of-function TP53 CDKN2A inactivation with frequent copy number including 3q26/28 11q13/22. A...
Urothelial carcinoma of the bladder is a common malignancy that causes approximately 150,000 deaths per year worldwide. So far, no molecularly targeted agents have been approved for treatment disease. As part The Cancer Genome Atlas project, we report here an integrated analysis 131 urothelial carcinomas to provide comprehensive landscape molecular alterations. There were statistically significant recurrent mutations in 32 genes, including multiple genes involved cell-cycle regulation,...
<h2>Summary</h2> Papillary thyroid carcinoma (PTC) is the most common type of cancer. Here, we describe genomic landscape 496 PTCs. We observed a low frequency somatic alterations (relative to other carcinomas) and extended set known PTC driver include <i>EIF1AX</i>, <i>PPM1D</i>, <i>CHEK2</i> diverse gene fusions. These discoveries reduced fraction cases with unknown oncogenic from 25% 3.5%. Combined analyses variants, expression, methylation demonstrated that different groups lead...
Liver cancer has the second highest worldwide mortality rate and limited therapeutic options. We analyzed 363 hepatocellular carcinoma (HCC) cases by whole-exome sequencing DNA copy number analyses, we 196 HCC methylation, RNA, miRNA, proteomic expression also. mutation analysis identified significantly mutated genes, including LZTR1, EEF1A1, SF3B1, SMARCA4. Significant alterations or downregulation hypermethylation in genes likely to result metabolic reprogramming (ALB, APOB, CPS1) were...
We sequenced the 29,751-base genome of severe acute respiratory syndrome (SARS)âassociated coronavirus known as Tor2 isolate. The sequence reveals that this is only moderately related to other coronaviruses, including two human HCoV-OC43 and HCoV-229E. Phylogenetic analysis predicted viral proteins indicates virus does not closely resemble any three previously groups coronaviruses. will aid in diagnosis SARS infection humans potential animal hosts (using polymerase chain reaction...
Anopheles gambiae is the principal vector of malaria, a disease that afflicts more than 500 million people and causes 1 deaths each year. Tenfold shotgun sequence coverage was obtained from PEST strain A. assembled into scaffolds span 278 base pairs. A total 91% genome organized in 303 scaffolds; largest scaffold 23.1 There substantial genetic variation within this strain, apparent existence two haplotypes approximately equal frequency ("dual haplotypes") fraction likely reflects outbred...
An estimated 15% or more of the cancer burden worldwide is attributable to known infectious agents. We screened colorectal carcinoma and matched normal tissue specimens using RNA-seq followed by host sequence subtraction found marked over-representation Fusobacterium nucleatum sequences in tumors relative control specimens. F. an invasive anaerobe that has been linked previously periodontitis appendicitis, but not cancer. Fusobacteria are rare constituents fecal microbiota, have cultured...
Follicular lymphoma (FL) and diffuse large B-cell (DLBCL) are the two most common non-Hodgkin lymphomas (NHLs). Here we sequenced tumour matched normal DNA from 13 DLBCL cases one FL case to identify genes with mutations in NHL. We analysed RNA-seq data these another 113 NHLs candidate mutations, then re-sequenced confirm 109 multiple somatic mutations. Genes roles histone modification were frequent targets of mutation. For example, 32% 89% had MLL2, which encodes a methyltransferase, 11.4%...
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...
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.