A5088977635- Single-cell and spatial transcriptomics
- Cancer Genomics and Diagnostics
- RNA modifications and cancer
- Renal and related cancers
- Immune Cell Function and Interaction
- Prostate Cancer Diagnosis and Treatment
- RNA Research and Splicing
- Cancer-related molecular mechanisms research
- Sarcoma Diagnosis and Treatment
- Renal cell carcinoma treatment
- Pediatric Urology and Nephrology Studies
- Epigenetics and DNA Methylation
- Kidney Stones and Urolithiasis Treatments
- Neurofibromatosis and Schwannoma Cases
- Prenatal Screening and Diagnostics
- Acute Myeloid Leukemia Research
- Chromatin Remodeling and Cancer
- Immune cells in cancer
- Neuroblastoma Research and Treatments
- Urinary Bladder and Prostate Research
- Urologic and reproductive health conditions
- T-cell and B-cell Immunology
- Cancer-related gene regulation
- Genomics and Chromatin Dynamics
- Molecular Biology Techniques and Applications
Wellcome Sanger Institute
2017-2025
Colorado State University
2023-2024
McGill University Health Centre
2024
Jewish General Hospital
2024
Nunavik Regional Board of Health and Social Services
2024
Quotient Clinical (United Kingdom)
2024
United States Army Institute of Surgical Research
2023-2024
University of North Carolina at Chapel Hill
2023
Transnational Press London
2021
University of California, Riverside
2015-2019
Abstract We present GOseq, an application for performing Gene Ontology (GO) analysis on RNA-seq data. GO is widely used to reduce complexity and highlight biological processes in genome-wide expression studies, but standard methods give biased results data due over-detection of differential long highly expressed transcripts. Application GOseq a prostate cancer set shows that dramatically changes the results, highlighting categories more consistent with known biology.
Abstract Background Droplet-based single-cell RNA sequence analyses assume that all acquired RNAs are endogenous to cells. However, any cell-free contained within the input solution also captured by these assays. This sequencing of constitutes a background contamination confounds biological interpretation transcriptomic data. Results We demonstrate from this "soup" is ubiquitous, with experiment-specific variations in composition and magnitude. present method, SoupX, for quantifying extent...
Abstract Motivation Increasing numbers of large scale single cell RNA-Seq projects are leading to a data explosion, which can only be fully exploited through integration. A number methods have been developed combine diverse datasets by removing technical batch effects, but most computationally intensive. To overcome the challenge enormous datasets, we BBKNN, an extremely fast graph-based integration algorithm. We illustrate power BBKNN on mouse atlasing data, and favourably benchmark its run...
Messenger RNA encodes cellular function and phenotype. In the context of human cancer, it defines identities malignant cells diversity tumor tissue. We studied 72,501 single-cell transcriptomes renal tumors normal tissue from fetal, pediatric, adult kidneys. matched childhood Wilms with specific fetal cell types, thus providing evidence for hypothesis that are aberrant cells. carcinoma, we identified a canonical cancer transcriptome little-known subtype proximal convoluted tubular cell....
Immune landscape of the human kidney Single-cell RNA sequencing has begun to shed light on full cellular diversity specific organs. However, these studies rarely examine organ-specific immune cells. Stewart et al. sequenced healthy adult and fetal samples at a single-cell level define heterogeneity in epithelial, myeloid, lymphoid From this dataset, they identified zonation cells, with relevance disease varied perturbations that occur different tumor settings. This profiling generates...
Transcriptional control is dependent on a vast network of epigenetic modifications. One mark particular interest tri-methylation lysine 27 histone H3 (H3K27me3), which catalysed and maintained by Polycomb Repressive Complex 2 (PRC2). Although this studied widely, the precise relationship between its local pattern enrichment regulation gene expression currently unclear. We have used ChIP-seq to generate genome-wide maps H3K27me3 enrichment, identified three profiles with distinct regulatory...
Abstract Osteosarcoma is a primary malignancy of bone that affects children and adults. Here, we present the largest sequencing study osteosarcoma to date, comprising 112 childhood adult tumours encompassing all major histological subtypes. A key finding our identification mutations in insulin-like growth factor (IGF) signalling genes 8/112 (7%) cases. We validate this observation using fluorescence situ hybridization (FISH) an additional 87 osteosarcomas, with IGF1 receptor ( IGF1R )...
Looping together genes in cancer A subset of human cancers are characterized by aberrant fusion two specific genes. In some cases, the activity resultant protein drives tumor growth. Most appear to arise from simple reciprocal chromosomal translocations. Anderson et al. found that characteristic gene a bone and soft tissue called Ewing sarcoma is produced far more complicated mechanism (see Perspective Imielinski Ladanyi). nearly half tumors examined, was created formation dramatic genomic...
Psoriatic arthritis (PsA) is a debilitating immune-mediated inflammatory of unknown pathogenesis commonly affecting patients with skin psoriasis. Here we use complementary single-cell approaches to study leukocytes from PsA joints. Mass cytometry demonstrates 3-fold expansion memory CD8 T cells in the joints compared peripheral blood. Meanwhile, droplet-based and plate-based RNA sequencing paired cell receptor alpha beta chain sequences show pronounced clonal expansions within Transcriptome...
Neuroblastoma is a childhood cancer that resembles developmental stages of the neural crest. It not established what processes neuroblastoma cells represent. Here, we sought to reveal phenotype by comparing ( n = 19,723) with normal fetal adrenal single-cell transcriptomes 57,972). Our principal finding was cell resembled sympathoblasts, but no other type. The sympathoblastic state universal feature cells, transcending cluster diversity, individual patients, and clinical phenotypes. We...
Tumor behavior is intricately dependent on the oncogenic properties of cancer cells and their multi-cellular interactions. To understand these dependencies within wider microenvironment, we studied over 270,000 single-cell transcriptomes 100 microdissected whole exomes from 12 patients with kidney tumors, prior to validation using spatial transcriptomics. Tissues were sampled multiple regions tumor core, tumor-normal interface, normal surrounding tissues, peripheral blood. We find that...
No AccessJournal of UrologyAdult Urology: Urolithiasis/Endourology1 Jul 2004METABOLIC RISK FACTORS AND THE IMPACT OF MEDICAL THERAPY ON MANAGEMENT NEPHROLITHIASIS IN OBESE PATIENTS WESLEY O. EKERUO, YEH HONG TAN, MATTHEW D. YOUNG, PHILIPP DAHM, MICHAELLA E. MALONEY, BARBARA J. MATHIAS, DAVID M. ALBALA, and GLENN PREMINGER EKERUOWESLEY EKERUO , TANYEH TAN YOUNGMATTHEW YOUNG DAHMPHILIPP DAHM MALONEYMICHAELLA MALONEY MATHIASBARBARA MATHIAS ALBALADAVID ALBALA PREMINGERGLENN View All Author...
Chordoma is a malignant, often incurable bone tumour showing notochordal differentiation. Here, we defined the somatic driver landscape of 104 cases sporadic chordoma. We reveal duplications transcription factor brachyury (T) in up to 27% cases. These variants recapitulate rearrangement architecture pathogenic germline T that underlie familial In addition, find potentially clinically actionable PI3K signalling mutations 16% Intriguingly, one most frequently altered genes, mutated exclusively...
A childhood tumor—from the beginning Many adult cancers arise from clonal expansions of mutant cells in normal tissue. These premalignant are defined by somatic mutations shared cancers. Whether pediatric originate a similar way is unknown. Coorens et al. studied Wilms tumor, kidney cancer. Phylogenetic analyses revealed large clones histologically and functionally tissue long before tumor development. Thus, like tumors, appears to bed. Science , this issue p. 1247
Dravet syndrome is a devastating genetic brain disorder caused by heterozygous loss-of-function mutation in the voltage-gated sodium channel gene SCN1A. There are currently no treatments, but upregulation of SCN1A healthy allele represents an appealing therapeutic strategy. In this study we identified novel, evolutionary conserved mechanism controlling expression that mediated antisense non-coding RNA (SCN1ANAT). Using oligonucleotide-based compounds (AntagoNATs) targeting SCN1ANAT were able...
The transcription factor FOS has long been implicated in the pathogenesis of bone tumours, following discovery that viral homologue, v-fos, caused osteosarcoma laboratory mice. However, mutations have not found human bone-forming tumours. Here, we report recurrent rearrangement and its paralogue, FOSB, most common benign tumours bone, osteoblastoma osteoid osteoma. Combining whole-genome DNA RNA sequences, find five FOSB one tumour. Extending our findings into a cohort 55 cases, using FISH...
The mammary epithelium is a dynamic, highly hormone-responsive tissue. To explore chromatin modifications underlying its lineage specification and hormone responsiveness, we determined genome-wide histone methylation profiles of epithelial subpopulations in different states. marked differences H3K27 trimethylation between the adult gland suggest that cell-fate decisions are orchestrated by polycomb-complex-mediated repression. Remarkably, epigenome underwent specific changes hormonal...
Abstract Background Droplet based single-cell RNA sequence analyses assume all acquired RNAs are endogenous to cells. However, any cell free contained within the input solution also captured by these assays. This sequencing of constitutes a background contamination that confounds biological interpretation transcriptomic data. Results We demonstrate from this ‘soup’ is ubiquitous, with experiment-specific variations in composition and magnitude. present method, SoupX, for quantifying extent...
Over 250 million people suffer from schistosomiasis, a tropical disease caused by parasitic flatworms known as schistosomes. Humans become infected free-swimming, water-borne larvae, which penetrate the skin. The earliest intra-mammalian stage, called schistosomulum, undergoes series of developmental transitions. These changes are critical for parasite to adapt its new environment it navigates through host tissues reach niche, where will grow reproductive maturity. Unravelling mechanisms...
Abstract Malignant rhabdoid tumour (MRT) is an often lethal childhood cancer that, like many paediatric tumours, thought to arise from aberrant fetal development. The embryonic root and differentiation pathways underpinning MRT are not firmly established. Here, we study the origin of by combining phylogenetic analyses single-cell mRNA studies in patient-derived organoids. Comparison somatic mutations shared between surrounding normal tissues places a lineage with neural crest-derived Schwann...