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• Intra-prostatic tumour evolution, steps in metastatic spread and histogenomic associations revealed by integration of multi-region whole genome sequencing with histopathological features

  We performed whole genome sequencing on 42 prostate cancer samples from the prostate, seminal vesicles and regional lymph nodes of five treatment-naive patients with locally advanced disease who underwent radical prostatectomy. Using cancer cell fractions computed from single nucleotide variants and copy number alterations, we reconstructed the tumour phylogenies, which in turn allowed us to infer key molecular steps in the progression of prostate cancer in these individuals. We mapped the clonal composition of cancer sampled across the prostate in each individual and inferred the routes of spread of cancer cells within the prostate and to seminal vesicles and lymph nodes.

  Study EGAS00001007438

• Detection and genomic analysis of BRAF fusions in Juvenile Pilocytic Astrocytoma through the combination and integration of multi-omic data

  Juvenile Pilocytic Astrocytoma (JPAs) are highly vascular tumors and show pervasive immune infiltration, which can lead to low tumor cell purity in clinical samples. In some instances, this results in gene fusions that are difficult to detect with conventional omics approaches including RNA-Seq. To this effect, we applied RNA-Seq as well as linked-read whole-genome sequencing and in situ Hi-C as new approaches to detect and characterize low-frequency gene fusions at the genomic, transcriptomic and spatial level. Overall, we demonstrate the power of integrating multi-omic datasets to identify low frequency fusions and characterize the JPA genome at high resolution.

  Study EGAS00001006388

• Dual spatially resolved transcriptomics for human host-pathogen colocalization studies in FFPE tissue sections

  Technologies to study localized host-pathogen interactions are urgently needed. Here, we present a spatial transcriptomics approach to simultaneously capture host and pathogen transcriptome-wide spatial gene expression information from human formalin-fixed paraffin-embedded (FFPE) tissue sections at a near single-cell resolution. We demonstrate this methodology in lung samples from COVID-19 patients and validate our spatial detection of SARS-CoV-2 against RNAScope and in situ sequencing. Host-pathogen colocalization analysis identified putative modulators of SARS-CoV-2 infection in human lung cells. Our approach provides new insights into host response to pathogen infection through the simultaneous, unbiased detection of two transcriptomes in FFPE samples.

  Study EGAS00001006186

• Genetic Variation and Signatures of Natural Selection in Diverse Africans

  Our study identified candidate regions of genome involved in adaptation and identified regions associated with selected phenotypes.

  Study phs000449

• Chemosensitive Relapse in Small Cell Lung Cancer Patient-Derived Xenografts

  Genetic and epigenetic analysis of patient-derived xenograft models of acquired chemoresistance in small cell lung cancer.

  Study phs001249

• Mutation analysis using AVENIO Expanded in cfDNA

  High resolution mutation analysis using the AVENIO ctDNA Expanded Kit V2, which targets 77 cancer-associated genes, in cfDNA in metastatic breast cancer.

  Dataset EGAD50000001669

• Fungal infection in Parkinson's disease.

  Isolation of fungi in infected neural tissues in patients with Parkinson's disease. Here we used next generation sequencing of Internal Transcribed Spacer (ITS) regions, by PCR amplicons (NGS ITS amplicon analysis).

  Dataset EGAD00001005025

• RNA-Seq datasets in human islets cultured in low glucose conditions

  7 RNA-Seq datasets in human pancreatic islets from 7 donors, where islets were using low (4mM) glucose conditions.

  Dataset EGAD00001005208

• NHLBI TOPMed: Australian Familial Atrial Fibrillation Study

  In the Australian Familial AF Study, a cohort of probands with familial AF was recruited for genetics studies at the Victor Chang Cardiac Research Institute. Familial AF cases were identified from in-patient and out-patient populations at St. Vincent's Hospital and by referral from collaborating physicians throughout Australia. Study subjects underwent clinical evaluation with history, ECG and echocardiogram, and informed consent was obtained from all participants. 151 probands aged <66 years at the time of diagnosis were included in this analysis. The control cohort was comprised of age- and sex-matched individuals (n=151) who had no history of cardiovascular disease. In the current TOPMed study, we have performed whole genome sequencing in European Ancestry cases with early-onset atrial fibrillation (defined as atrial fibrillation onset prior to 61 years).

  Study phs001435

• The Mutational Landscape of Head and Neck Squamous Cell Carcinoma

  This study was the first-known large-scale effort to uncover the mutational spectrum of head and neck cancers. We analyzed whole-exome sequence from 92 tumor-normal pairs and retained 74 of them for significance analysis. The majority exhibited a mutational profile consistent with tobacco exposure; human papilloma virus sequence was detectable in 15% of cases. In addition to identifying previously known HNSCC genes (TP53, CDKN2A, PTEN, PIK3CA, and HRAS), the analysis revealed many genes not previously implicated in this malignancy. At least 30% of cases harbor mutations in genes (such as NOTCH1, IRF6, TP63) that regulate squamous differentiation, implicating alterations in this process as a major driver of HNSCC carcinogenesis. Altogether, the results suggest that large-scale exome sequencing may illuminate fundamental tumorigenic mechanisms with important therapeutic implications.

  Study phs000370